Cystic papillary adenoma of the seminal vesicle.

BACKGROUND: Primary Seminal Vesicle (SV) tumours are a rare entity, with most SV masses representing invasion of the SV by malignancy originating in an adjacent organ, most often the prostate. Previously reported primary SV epithelial tumours have included adenocarcinoma and cystadenoma, with limited prior reports of inracystic papillary structures. CASE PRESENTATION: A 35-year-old male presented with azoospermia, intermittent macroscopic haematuria, and mild right iliac fossa and groin pain. A papillary appearing seminal vesicle mass was found on imaging and seminal vesicoscopy. The mass was robotically excised with diagnosis of benign cystic papillary adenoma made. CONCLUSION: In this manuscript we describe a rare case of a benign cystic papillary adenoma of the seminal vesicle, a unique histological entity differentiated from cystadenoma of the Seminal Vesicle by its papillary component.

A systematic scoping review of multidisciplinary cancer team and decision-making in the management of men with advanced prostate cancer.

PURPOSE: The early diagnosis of prostate cancer and subsequent access to the treatment options helps to achieve optimal cancer outcomes. As the treatment options for patients with advanced prostate cancer continues to evolve, patients need to access a multidisciplinary team (MDT) meeting to receive best-practice care. METHODS: In this paper a MEDLINE review was performed to assess clinical decision making in the context of MDT discussions for patients with advanced prostate cancer. RESULTS: From 441 returned articles and abstracts, 50 articles were assessed for eligibility and 16 articles included for analysis. Sixteen articles were identified, 9 of the 16 articles used quantitative methodology including three retrospective analysis of clinical registry data, patient medical records and/or MDT meeting notes and three cross-sectional surveys. Other study designs included one observation study and one study using a combination of qualitative and quantitative methodologies and one mini-review. There were also four editorials included in the review and two consensus statements. CONCLUSION: This paper highlights the important role the inter-disciplinary MDT has on shared decision making for men with advanced prostate cancer. The application of MDT care is a rapidly growing trend in uro-oncology and an efficient MDT service requires further research to assess its efficiency so that it may expand through all aspect of uro-oncology.

Clash of the calculators: External validation of prostate cancer risk calculators in men undergoing mpMRI and transperineal biopsy.

Objective: To compare the accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) RC, MRI-ERSPC-RC, and Prostate Biopsy Collaborative Group (PBCG) RC in patients undergoing transperineal prostate biopsy. Patients and methods: We identified 392 patients who underwent mpMRI before transperineal prostate biopsy across multiple public and private institutions between January 2017 and August 2019. The estimated probabilities of detecting PCa and significant PCa were calculated using the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC. Receiver operating characteristic (ROC) curves for each calculator were generated and the area underneath the curve (AUC) was compared. Calibration and clinical utility were assessed with calibration plots and decision curve analysis, respectively. Results: PCa was detected in 285 patients (72.7%) with significant PCa found in 200 patients (51.1%). ROC curve analysis found the MRI-ERSPC-RC outperformed the ERSPC-RC and PBCG-RC. For the prediction of PCa, the AUC was 0.756, 0.696, and 0.675 for the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC, respectively. The AUC for the prediction of significant PCa was 0.803, 0.745, and 0.746 for the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC, respectively. Conclusions: Our study validated the ERSPC-RC, MRI-ERSPC-RC, and PBCG-RC in a cohort undergoing transperineal prostate biopsy with the MRI-ERSPC-RC performing the best. These RCs may enable improved shared decision making and help to guide patient selection for biopsy.

Assessment of Intrafraction Motion of the Urinary Bladder Using Magnetic Resonance Imaging (cineMRI).

AIM: To assess the intrafraction motion of the urinary bladder and delineate the appropriate margin size for radiotherapy planning, for both the full and empty bladder. MATERIALS AND METHODS: This was a single-site, single-arm study of 20 patients planned to undergo radical cystectomy for histologically confirmed muscle-invasive bladder cancer. Patients underwent magnetic resonance imaging (cineMRI) of the entire pelvis using a 3-Tesla system, prior to cystectomy. Patients first underwent a cineMRI with a full bladder, then voided and underwent a second MRI with an empty bladder. All MRI sequences were acquired over 18 min. We assessed the differences in bladder filling and subsequent bladder wall displacement, between the empty and full bladder, during a time period consistent with radiotherapy treatment delivery. RESULTS: Twenty patients underwent cineMRI of the entire pelvis. The maximum mean directional displacements of the bladder walls over the 18 min duration of the scan for the empty bladders were 9.8 mm superiorly, 1.1 mm inferiorly, 2.39 mm anteriorly, 3.73 mm posteriorly, 2.74 mm to the left and 2.48 mm to the right. The maximal mean displacements for the full bladders were 9.2 mm superiorly, 1.1 mm inferiorly, 2.28 mm anteriorly, 1.08 mm posteriorly, 1.85 mm to the left and 1.73 mm to the right. Statistically significant differences were seen in the posterior, left and right displacements but were quantitatively small. CONCLUSIONS: Intrafractional motion secondary to bladder filling showed minimal variation between the full and empty bladder. Similar clinical target volume to planning target volume margins can be applied for the delivery of radiotherapy for a full and empty bladder.

Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE): a cost minimisation analysis.

PURPOSE: A cost minimisation analysis compares the costs of different interventions' to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE). METHODS: The Evolution registry is a prospective, multicentre registry, conducted by the European Association of Urology Research Foundation (EAUrf) for 24 months in 5 European countries. Evolution was designed to register the management of symptomatic BPE in clinical practice settings in 5 European countries. Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed. RESULTS: In total, 1838 men were enrolled with 1246 evaluable at 24 months. Medical therapies were more cost saving than TURP for treatment durations ranging from 2.9 to 70.4 years. Cost saving depended on both medication class and individual country assessed. Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy. Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain. Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany. CONCLUSIONS: BPE medical management was more cost saving than TURP for different specific treatment durations. Information from this study will allow clinicians to convey medical and surgical costs over time, to both patients and payors alike, when considering BPE treatment.

Miniaturised percutaneous nephrolithotomy versus flexible ureteropyeloscopy: a systematic review and meta-analysis comparing clinical efficacy and safety profile.

PURPOSE: This study aims to comparatively evaluate clinical outcomes of mini-PCNL and FURS for treating urinary tract calculi in a single session. METHODS: A systematic search using electronic databases was performed for studies comparing mini-PCNL and FURS for the treatment of urinary tract calculi. The primary outcome measurements were stone-free rates (SFRs) and complication rates for both techniques. Secondary outcome measurements were to compare patient demographics, operative duration, and inpatient stay. Meta-analysis was performed with Review Manager version 5.3 software. RESULTS: Sixteen studies on 1598 patients (n = 877 for mini-PCNL and n = 721 for FURS) met inclusion criteria. Demographics including age (p = 0.26), body mass index (BMI) (p = 0.51), and gender ratio (p = 0.6), were similar in both groups. Overall, SFR was significantly greater in the mini-PCNL group compared to the FURS group (n = 763/877, 89.3 ± 8.4% versus n = 559/721, 80.1 ± 13.3% [OR 2.01; 95% CI 1.53-2.64; p < 0.01]). Duration of inpatient stay was significantly greater in the mini-PCNL group compared to the FURS group (n = 877, 4 ± 1.6 days versus n = 721, 2.5 ± 2.2 days, respectively [WMD: 1.77; 95% CI 1.16-2.38, p < 0.01]. Overall complication rates were not significantly different between mini-PCNL and FURS (n = 171/877, 19.5 ± 19.1% versus n = 112/721, 15.5 ± 18.9%, respectively [OR 1.43; 95% CI 0.85-2.4, p = 0.18]). CONCLUSIONS: Mini-PCNL is associated with greater SFRs and longer inpatient stay compared to FURS. Complication rates were similar for both techniques. The advantages and disadvantages of both technologies should be familiar to urologists and conveyed to patients prior to urological intervention for nephrolithiasis.

Prostatic artery embolization for benign prostatic obstruction: assessment of safety and efficacy.

PURPOSE: Prostatic artery embolization (PAE) has seen a recent increase in interest as a treatment for men with benign prostatic obstruction (BPO). The appeal of this intervention lies in reported reduction in morbidity and its minimally invasive nature. The purpose of this review is to assess the safety and efficacy of PAE as a new treatment in BPO and explore risks surrounding its performance. METHODS: A review of the literature was performed. Medical databases searched included PubMed, EMBASE, and Cochrane databases, limited to English, peer-reviewed articles. Search terms included prostatic artery embolization, lower urinary tracts symptoms, minimally invasive therapies, interventional radiology prostate, and benign prostatic hyperplasia. Articles were screened by two independent reviewers for content on development, methods, outcomes, and complications of PAE. RESULTS: Suitability of patients to undergo PAE depends on review of patient history, pre-procedure visualisation of appropriate vascular anatomy and clinical parameters. Despite this selection of candidates favourable for procedural success, PAE is not without risk of complications, some of which can significantly affect patient quality of life. CONCLUSIONS: Although initial findings show promise regarding safety and efficacy of PAE in improving symptom and quality-of-life scores, further investigation is required to establish durability of effect and the appropriate use of this experimental modality. There is currently limited robust evidence for the beneficial outcomes of PAE. Long-term follow-up studies will add to the evidence base to help further assess the feasibility of this procedure as an alternative to TURP.

Urinary Bladder vs Gastrointestinal Tissue: A Comparative Study of Their Biomechanical Properties for Urinary Tract Reconstruction.

OBJECTIVE: To evaluate the mechanical properties of gastrointestinal (GI) tissue segments and to compare them with the urinary bladder for urinary tract reconstruction. METHODS: Urinary bladders and GI tissue segments were sourced from porcine models (n = 6, 7 months old [5 male; 1 female]). Uniaxial planar tension tests were performed on bladder tissue, and Cauchy stress-stretch ratio responses were compared with stomach, jejunum, ileum, and colonic GI tissue. RESULTS: The biomechanical properties of the bladder differed significantly from jejunum, ileum, and colonic GI tissue. Young modulus (kPa-measure of stiffness) of the GI tissue segments was on average 3.07-fold (±0.21 standard error) higher than bladder tissue (P < .01), and the strain at Cauchy stress of 50 kPa for bladder tissues was on average 2.27-fold (±0.20) higher than GI tissues. There were no significant differences between the averaged stretch ratio and Young modulus of the horizontal and vertical directions of bladder tissue (315.05 ± 49.64 kPa and 283.62 ± 57.04, respectively, P = .42). However, stomach tissues were 1.09- (±0.17) and 0.85- (±0.03) fold greater than bladder tissues for Young modulus and strain at 50 kPa, respectively. CONCLUSION: An ideal urinary bladder replacement biomaterial should demonstrate mechanical equivalence to native tissue. Our findings demonstrate that GI tissue does not meet these mechanical requirements. Knowledge on the biomechanical properties of bladder and GI tissue may improve development opportunities for more suitable urologic reconstructive biomaterials.

Single-use flexible ureteropyeloscopy: a systematic review.

PURPOSE: Data assessing the effectiveness of single-use flexible ureteropyeloscopy (FURS) are limited. This study evaluates and compares single-use FURS with conventional reusable FURS. METHODS: A systematic search using electronic databases (Pubmed and Embase) was performed for studies evaluating single-use FURS in the setting of urinary tract stone disease. Outcome measures included a comparative evaluation of their mechanical, optical and clinical outcomes. RESULTS: Eleven studies on 466 patients met inclusion criteria. In vitro comparative data were available on three single-use flexible ureteropyeloscopes (LithoVue™, Polyscope™ and SemiFlex™) and clinical data were available on two (LithoVue™ and Polyscope™). The overall stone-free rate and complication rate associated with single-use FURS was 87 ± 15% and 9.3 ± 9%, respectively. There were no significant differences in procedure duration, stone size, stone clearance and complication rates when single-use FURS and reusable FURS were compared (duration: 73 ± 27 versus 74 ± 13 min, p = 0.99; stone size: 1.36 ± 0.2 versus 1.34 ± 0.18 cm, p = 0.93; stone-free rate: 77.8 ± 18 versus 68.5 ± 33%, p = 0.76; complication rate 15.3 ± 10.6 versus 15 ± 1.6%, p = 0.3). CONCLUSIONS: Single-use FURS demonstrates comparable efficacy with reusable FURS in treating renal calculi. Further studies on clinical efficacy and cost are needed to determine whether single-use FURS will reliably replace its reusable counterpart.

Total and beverage-specific alcohol intake and the risk of aggressive prostate cancer: a case-control study.

BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its association with aggressive prostate cancer (APC) is uncertain. Recent studies have shown a modest increase in risk of APC associated with heavy alcohol intake while association for beverage types remain inconsistent. METHODS: Using a case-control design and self-administered questionnaire, we examined the association between APC (high grade and/or advanced stage) and frequency and quantity of alcohol intake 2 years prior to enrolment. Furthermore, we delineated the relationships for beverage-specific intakes of beer, red wine, white wine and spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake frequency of ⩾5 days per week was associated with increased risk compared with no beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine was protective at all frequencies of consumption compared with those with no wine intake. For every 10 g per week ethanol intake from beer increase, the odds of advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was observed for red or white wine while a marginal dose-response relationship was found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and possibly spirits consumption is associated with increased risk while no dose-response relationship was found for red or white wine. Wine drinkers at all frequencies have a decreased risk of APC compared with those who did not drink wine.

Health information quality on the internet in gynecological oncology: a multilingual evaluation.

BACKGROUND: Oncological internet information quality is considered variable, but no comprehensive analysis of gynecological malig- nancies exists. The present authors' objectives were to compare the quality of common malignancy websites and to assess for language or disease differences; and secondly, to perform a quality comparison between medical and layperson terminology. MATERIALS AND METHODS: World Health Organization (WHO) Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.Google.com) 8,400 websites were assessed using keywords 'endometrial, 'uterine', 'cervical', 'ovarian', 'vaginal', 'vulvar', plus 'cancer', in English, French, German, and Spanish; repeated for alternate terms e.g. 'cervix', 'womb'. RESULTS: Searches for "vaginal' 'uterine', 'cervical', and 'endometrial' each returned millions of websites. The total percentage of all assessed HON-accredited sites was notably low across all search terms (median 15%; range 3-19%). Significant differences by malignancy type (p < 0.0001), language (p < 0.0001), and tertiles (thirds) of the first 150 websites returned (p < 0.0001). French language had most accredited websites. Using alternate terms demonstrated significant differences (p < 0.001) in accredited websites for most gynecological cancers. CONCLUSIONS: Internet data on gynecological malignancies is overwhelming. Further, a lack of validation of the majority of gynecological oncologic sites should be appreciated with discrepancies in quality and number of websites across diseases, languages, and also between medical and layperson terms. Physicians should encourage and more importantly their professional bodies should participate in the development of informative, ethical, and reliable health websites on the internet and direct patients to them.

Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis?

BACKGROUND: Multidrug-resistant gram-negative bacterial (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating transrectal ultrasound (TRUS)-guided prostate biopsy. Fluoroquinolone-based regimens, once the mainstay of many protocols, are increasingly ineffective. Fosfomycin has reasonable in vitro and urinary activity (minimum inhibitory concentration breakpoint ≤64 µg/mL) against MDR-GNB, but its prostatic penetration has been uncertain, so it has not been widely recommended for the prophylaxis or treatment of MDR-GNB prostatitis. METHODS: In a prospective study of healthy men undergoing a transurethral resection of the prostate for benign prostatic hyperplasia, we assessed serum, urine, and prostatic tissue (transition zone [TZ] and peripheral zone [PZ]) fosfomycin concentrations using liquid chromatography-tandem mass spectrometry, following a single 3-g oral fosfomycin dose within 17 hours of surgery. RESULTS: Among the 26 participants, mean plasma and urinary fosfomycin levels were 11.4 ± 7.6 µg/mL and 571 ± 418 µg/mL, 565 ± 149 minutes and 581 ± 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 ± 4.9 µg/g (range, 0.7-22.1 µg/g), with therapeutic concentrations detectable up to 17 hours following the dose. The mean prostate to plasma ratio was 0.67 ± 0.57. Mean concentrations within the TZ vs PZ prostate regions varied significantly (TZ, 8.3 ± 6.6 vs PZ, 4.4 ± 4.1 µg/g; P = .001). Only 1 patient had a mean prostatic fosfomycin concentration of <1 µg/g, whereas the majority (70%) had concentrations ≥4 µg/g. CONCLUSIONS: Fosfomycin appears to achieve reasonable intraprostatic concentrations in uninflamed prostate following a single 3-g oral dose, such that it may be a potential option for prophylaxis pre-TRUS prostate biopsy and possibly for the treatment of MDR-GNB prostatitis. Formal clinical studies are now required.

Interval to biochemical recurrence following radical prostatectomy does not affect survival in men with low-risk prostate cancer.

OBJECTIVES: To evaluate the temporal relationship between interval to biochemical recurrence (BCR) following radical prostatectomy (RP) and prostate cancer-specific mortality (PCSM). PATIENTS AND METHODS: The study comprised of 2,116 men from the Victorian Radical Prostatectomy Register, a whole-of-population database of all RPs performed between 1995 and 2000 in Victoria, Australia. Follow-up prostate-specific antigen and death data were obtained via record linkage to pathology laboratories and the Victorian Registry of Births, Deaths and Marriages. Poisson regression models with PCSM as the outcome were fit to the data. Models included age at surgery, Gleason score and tumour stage as covariates. RESULTS: Median post-surgery and post-BCR follow-up was 10.3 and 7.5 years, respectively. 695 men (33 %) experienced BCR during follow-up, of which 82 % occurred within 5 years of RP; 66 men died from prostate cancer. Men with combined high Gleason sum (≥4 + 3) and extra-prostatic (≥pT3a) disease had substantially increased mortality rate with early BCR, while those experiencing BCR after a longer interval had significantly lower mortality. Men with combined low Gleason sum (≤3 + 4) and organ-confined disease (≤pT2c) risk disease were not at any substantial risk of death in this time frame regardless of timing of BCR following RP. CONCLUSIONS: This study evaluates the temporal relationship between BCR and PCSM using a whole-of-population cohort of men treated with RP. Men with low-risk features of prostate cancer at time of RP have low mortality even if they experience early BCR. This subgroup may be counselled regarding their favourable long-term prognosis.

Radical cystectomy and orthotopic bladder substitution: surgical tricks and management of complications.

AIM: Bladder cancer is the second most common urological malignancy, with urothelial carcinoma (transitional cell carcinoma) comprising almost 90% of all primary bladder tumours. Over recent decades, radical cystectomy has emerged as the predominant treatment modality for patients with high-grade, invasive urothelial cancers and for those with less-invasive disease who fail treatment with bladder-preservation strategies. Bladder substitution following radical cystectomy has become increasingly common and in many centers has evolved to become the standard method of urinary diversion. The main goal of this paper is to review intraoperative considerations for patients undergoing radical cystectomy with a focus on issues specific to surgical tricks with neobladder construction and postoperative complications. METHODS: Systematic literature review in Pubmed and Embase including bladder cancer, urinary diversion, neobladder, surgical technique and complications as key words. RESULTS: Intraoperative techniques and modifications have made neobladder construction more amenable and the standard in suitable patients. Postoperative complications still occur in a significant number of patients but may be minimised and recognised early for better outcomes. CONCLUSION: Orthotopic bladder substitution does not compromise oncological outcome and importantly can be performed with relatively good results regarding functional and quality of life issues. Modifications to intraoperative technique can assist with neobladder construction to aid better outcomes. Where possible orthotopic bladder substitution should be the diversion of choice. Of paramount importance is the active postoperative management and regular long-term follow-up of patients with an orthotopic bladder substitution.

Current role of salvage robotic-assisted laparoscopic prostatectomy.

OBJECTIVES: Salvage Robotic-Assisted Laparoscopic Prostatectomy (sRALP) is a treatment option for biochemical recurrence (BCR) in prostate cancer. It is a new and presently uncommonly performed procedure, which may be technically challenging. We aim to summarise the current literature regarding sRALP with specific reference to patient selection, complications and peri-operative functional and oncological outcomes. METHODS: A comprehensive and critical review of all peer-reviewed publications regarding sRALP. RESULTS: Within the body of literature, we identified six low-volume case-series studies analysing outcomes of sRALP. Overall, peri-operative outcomes were encouraging with low complication rates and estimated blood loss (EBL) equivocal to open and laparoscopic salvage radical prostatectomy (sRP). Long-term follow-up for functional and oncological outcomes was limited. From the limited follow-up data, the current sRALP studies show similar BCR compared to large-volume open sRP series. Potency outcomes were poor post-sRALP. CONCLUSIONS: Salvage Robotic-Assisted Laparoscopic Prostatectomy is a technically feasible operation with a low risk of significant associated complications. Robotic technology can aid the surgeon in salvage prostatectomy. Data on functional and oncological outcomes lack long-term information but initial results are encouraging. Larger series with longer follow-up periods are necessary to draw significant conclusions about the efficacy of sRALP.

The effect of urea and ammonia treatments on the survival of Salmonella spp. and Yersinia enterocolitica in pig slurry.

AIMS: The objective of this study was to investigate the survival of Salmonella and Yersinia enterocolitica strains in pig slurry and evaluate urea and ammonia as disinfection strategies. METHODS AND RESULTS: Salmonella Anatum, Salmonella Derby, Salmonella Typhimurium DT19 and Y. enterocolitica bioserotypes 4, O:3, 2, O:5,27 and 1A, O:6,30 were selectively marked by insertion of the plasmid, pGLO encoding for green fluorescent protein and for ampicillin resistance. Strain cocktails were inoculated into fresh pig slurry (control), slurry treated with urea [final concentration 2% w/w, (0.33 mol l(-1) )] and slurry treated with ammonia [final concentration 0.5% w/w, (0.3 mol l(-1) )] and stored at 4, 14 and 25°C. Bacterial counts were determined at regular intervals on xylose lysine deoxycholate agar (XLD), and XLD supplemented with ampicillin (0.1 mg ml(-1) ) and arabinose (0.6 mg ml(-1) ) for Salmonella and cefsulodin-irgasan-novobiocin agar (CIN) and CIN supplemented with ampicillin and arabinose for Y. enterocolitica. The pH of the control-, urea- and ammonia-treated samples ranged from 7.1 to 7.7, 8.8 to 8.9 and 8.0 to 8.3, respectively. Salmonella D(4) values ranged from 2.71 to 21.29 days, D(14) values from 2.72 to 11.62 days and D(25) values from 1.76 to 6.85 days. The equivalent D values ranges for the Y. enterocolitica strains were 3.7-19.23, 1.8-16.67 and 1.63-7.09 days, respectively. Treatment significantly (P < 0.01) affected D values with control > ammonia > urea, as did incubation temperature; 4 > 14 > 25°C. CONCLUSIONS: Urea and to a lesser extent ammonia may be used to disinfect Salmonella- and/or Y. enterocolitica-contaminated pig slurry, decreasing the storage time required while increasing its fertilizer value. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents data supporting the treatment of pig slurry to kill important zoonotic agents, thereby reducing environmental contamination, cross-infection of other animals and decreasing zoonotic disease in the food chain.

Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge.

Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus. We aimed to generate strong mucosal immune responses to simian immunodeficiency virus (SIV) in rhesus macaques by targeting recombinant adenovirus serotype 5 (rAd5) to the lung. The immunogenicity and efficacy of aerosol (AE) vaccination was compared with intramuscular (IM) delivery in either an intravenous (IV) or intrarectal (IR) SIV(mac251) challenge model. Aerosolized rAd5 induced strong cellular responses in the lung and systemic humoral responses equivalent to IM. Strikingly, all immunization groups controlled acute viremia in the IV challenge model by 1-2 logs. By contrast, after IR challenge, only peak viremia was reduced by immunization, with no significant effect on SIV infection acquisition rate or mucosal CD4(+) T-cell preservation. Improved disease outcome was associated with pre-challenge cellular and humoral responses, while post-challenge T-cell responses were highly correlated with viremia control. The similar outcomes achieved by systemic and airway mucosal immunization support AE delivery as a safe, effective, and less invasive alternative to parenteral vaccination.