Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune responses that correlate with safety and may be associated to therapy potential.

Background: Standard of care treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette Guérin (BCG) is associated with side effects, disease recurrence/progression and supply shortages. We recently showed in a phase I trial (NCT03421236) that intravesical instillation in patients with NMIBC with the maximal tolerated dose of Ty21a/Vivotif, the oral vaccine against typhoid fever, might have a better safety profile. In the present report, we assessed the immunogenicity of intravesical Ty21a in patients of the clinical trial that had received the maximal tolerated dose and compared it with data obtained in patients that had received standard BCG.

Tumor-Microenvironment Characterization of the MB49 Non-Muscle-Invasive Bladder-Cancer Orthotopic Model towards New Therapeutic Strategies.

Bacillus Calmette-Guérin (BCG) instillations for the treatment of non-muscle-invasive bladder cancer patients can result in significant side effects and treatment failure. Immune checkpoint blockade and/or decreasing tumor-infiltrating myeloid suppressor cells may be alternative or complementary treatments. Here, we have characterized immune cell infiltration and chemoattractant molecules in mouse orthotopic MB49 bladder tumors.

Intravesical Ty21a Treatment of Non-muscle-invasive Bladder Cancer Shows a Good Safety Profile.

Unlabelled: Standard-of-care immunotherapy for non-muscle-invasive bladder cancer (NMIBC) with intravesical Bacillus CalmettteGuérin (BCG) is associated with adverse events (AEs), disease recurrence/progression, and supply shortages. Preclinical data have shown that intravesical instillation of Ty21a/Vivotif, the oral vaccine against typhoid fever, may be an effective and safer alternative to BCG. We assessed the safety of intravesical Ty21a in NMIBC.

Vδ2 T cells are associated with favorable clinical outcomes in patients with bladder cancer and their tumor reactivity can be boosted by BCG and zoledronate treatments.

Bladder cancer is an important public health concern due to its prevalence, high risk of recurrence and associated cost of management. Although BCG instillation for urothelial cancer treatment is the gold-standard treatment for this indication, repeated BCG treatments are associated with significant toxicity and failure, underlining the necessity for alternative or complementary immunotherapy and overall for better understanding of T-cell responses generated within bladder mucosa. Tumor-infiltrating lymphocytes (TIL) have long been recognized as a crucial component of the tumor microenvironment for the control of tumor.

Siglec-7 May Limit Natural Killer Cell-mediated Antitumor responses in Bladder Cancer Patients.

Unlabelled: Aberrant glycosylation actively contributes to tumor progression and is a key hallmark of cancer. Most of the glycan moieties expressed on the surface of cancer cells are sialic acids that may modulate antitumor immune responses binding to sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed by immune cells. Here we show that Siglecs may decrease the bladder tumor immune response mediated by natural killer (NK) cells.

Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients.

Among the growing family of inhibitory receptors regulating immunity, sialic acid-binding immunoglobulin domain-containing lectins (Siglecs) have recently emerged as immunoregulatory receptors recognizing sialylated ligands on tumor cell surface. However, their role in the immunoregulation of bladder cancer (BCa) remains unknown. Here, we determined the presence of eight Siglec ligands (SLs) on bladder nontumor and tumor cell lines.

The utility of in-bore multiparametric magnetic resonance-guided biopsy in men with negative multiparametric magnetic resonance-ultrasound software-based fusion targeted biopsy.

Objectives: To evaluate the utility of in-bore multiparametric magnetic resonance-guided biopsy of the prostate (IB) in patients with visible lesion/s and previous negative software-based multiparametric magnetic resonance imaging/ultrasonography fusion-targeted biopsy of the prostate (FTB).

Patients And Methods: We retrospectively analysed prospectively maintained database including consecutive men undergoing IB from March 2013 to October 2017 in 2 European centres expert in this procedure. We selected men with the following criteria: No previous treatment for prostate cancer (CaP), multiparametric magnetic resonance imaging (mpMRI) lesion(s) PIRADS score ≥ 3, FTB showing no clinically significant cancer (csCaP), and subsequent IB.

Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer.

Background: Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141), cDC2s (CD1c) and plasmacytoid DCs.

The utility of intraoperative contrast-enhanced ultrasound in detecting residual disease after focal HIFU for localized prostate cancer.

Background And Objectives: Focal high intensity focused ultrasound (HIFU) is an emerging treatment for selected men with localized prostate cancer. A limitation of HIFU is the absence of a reliable tool to measure treatment effect intraoperatively. Contrast-enhanced ultrasound (CEUS) has been shown to be a promising modality for assessing the extent and boundaries of tissue ablation.

[Management of urologic cancers in elderly people : which implications ?].

Elderly patients with urologic cancer are often undertreated because of their age. Recently, many studies showed that advanced age is not an absolute contraindication to radical surgery for bladder and prostate cancer patients. For small renal cancers, instead, active surveillance with a close follow-up may be a valid alternative to surgery because of a low risk of progression.

[Current surgical treatments for women with stress urinary incontinence].

Surgical treatments for female stress urinary incontinence is in perpetual evolution. This article reviews the current surgical treatments for stress urinary incontinence in female. Bulking agents, Burch colposuspension, autologous sling, midurethral slings, single incision slings, artificial urinary sphincter and adjustable continence therapy (ACT) are discussed.

Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8 T cells.

Background: Several mechanisms are present in the tumor microenvironment (TME) to impair cytotoxic T cell responses potentially able to control tumor growth. Among these, the accumulation of adenosine (Ado) contributes to tumor progression and represents a promising immunotherapeutic target. Ado has been shown to impair T cell effector function, but the role and mechanisms employed by Ado/Ado receptors (AdoRs) in modulating human peripheral and tumor-infiltrating lymphocyte (TIL) function are still puzzling.

Spoilt for Choice: A Survey of Current Practices of Surgical Urinary Stone Treatment and Adherence to Evidence-Based Guidelines among Swiss Urologists.

Introduction: Urologists have to master a variety of techniques to be able to offer the most appropriate surgical stone treatment for each individual patient. Therefore, we performed a survey among board-certified Swiss urologists to assess the availability of the different surgical methods, the current practices of surgical treatment of urolithiasis and the adherence to evidence-based guideline recommendations in Switzerland.

Methods: A 14-question survey assessed the working environment, equipment, perioperative settings and decision trees for specific stone scenarios.

Double Positive CD4CD8 T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization.

The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protective role, in contrast to Th2 CD4 T cells. Double positive (DP) CD4CD8 T cells remain understudied, although they were already described in human cancers, with conflicting data regarding their role.

Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell-Mediated Tumor Regression in the MB49 Bladder Cancer Model.

Preclinical data show that intravesical instillation of Ty21a/Vivotif, a commercial vaccine against typhoid fever, is an effective alternative option to standard Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC). Here, we characterized the inflammatory effects of Ty21a on the bladder and investigated the immune mechanisms underlying tumor regression toward the use of this bacterial vaccine in NMIBC patients. MB49 bladder tumor-bearing mice had significantly improved survival after intravesical instillations of Ty21a doses of 10 to 10 colony-forming units.

[Urology in 2018].

This article summarizes the milestones in urology in 2018 in the following areas : urinary tract infection, functional bladder disorders, oncology and renal colic treatment.

Reduction and follow-up of hospital discharge letter delay using Little's law.

Quality Problem: As discharge letters (DL) hold important information for healthcare professionals and especially for general practitioners, rapid and efficient finalization is required. We describe a project aiming to reduce DL submission within 8 days in our Urology Department (UD), as required by the local Hospital Board (HB).

Initial Assessment And Choice Of Solution: A team was built in UD with staff members and one external expert to study the root causes of delayed DL creation and develop sustainable strategies to improve and monitor the process, including habits changing, training and application of Little's Law.

[Ambulatory surgery in urology].

The volume of ambulatory surgery in urology increases every year. Successful ambulatory care is defined by low hospital (re)admission rates, insuring optimal oncologic and functional outcomes. New medical techniques such as minimally invasive surgical approaches and less side effects of anesthesia have helped the development of ambulatory surgery.

[Improved rehabilitation after major urological surgery : what role for the general practitioner ?].

Enhanced recovery after surgery (ERAS) is a multimodal concept aiming to reduce surgical stress and prevent postoperative complications. Once adapted to urologic patients in 2013, this protocol evolves continuously and many international centers have now implemented it. This article resumes ERAS key principles for general practitioners as they can have a significant impact on patient's optimization before surgery.

50-Gy Stereotactic Body Radiation Therapy to the Dominant Intraprostatic Nodule: Results From a Phase 1a/b Trial.

Purpose: Although localized prostate cancer (PCa) is multifocal, the dominant intraprostatic nodule (DIN) is responsible for disease progression after radiation therapy. PCa expresses antigens that could be recognized by the immune system. We therefore hypothesized that stereotactic dose escalation to the DIN is safe, may increase local control, and may initiate tumor-specific immune responses.

Intramuscular Immunization Induces Antigen-specific Antibodies in Urine.

Towards the development of vaccines against urinary tract infections (UTI), we determined the ability of intramuscular (i.m.) immunization to result in antigen-specific antibodies in urine.