Publications by authors named "Patrice Jichlinski"

122 Publications

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

Eur Urol Open Sci 2021 Dec 18;34:79-82. Epub 2021 Nov 18.

Department of Urology, Urology Research Unit, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

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. We observed higher NK cell activity against desialylated bladder tumor cell lines. We therefore determined the expression of nine Siglecs on circulatory NK cells from healthy donors and patients with bladder cancer (BCa). NK cells from blood mainly express Siglec-7, which is highly upregulated in non-muscle-invasive BCa (NMIBC), as well as Siglec-6, albeit at a much lower level. However, both Siglecs are expressed by urinary NK cells from NMIBC patients undergoing bacillus Calmette-Guérin therapy. analysis of Siglec-6 and Siglec-7 expression levels on tumor-infiltrating NK cells (TINKs) from BCa patients showed that only Siglec-7 is expressed by TINKs. Finally, analyses for The Cancer Genome Atlas data set revealed that BCa patients with high expression levels of Siglec-7 have a poor survival rate. This work indicates that Siglec-7 may restrain NK-mediated antitumor immunity in BCa.

Patient Summary: We investigated the expression of proteins called Siglecs in natural killer (NK) cells from patients with bladder cancer. We showed that levels of the protein Siglec-7 in blood, urine, and tumors from patients with bladder cancer are associated with poor clinical outcomes. Thus, Siglec-7 may be involved in the regulation of antitumor immunity mediated by NK cells in bladder cancer.
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http://dx.doi.org/10.1016/j.euros.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605422PMC
December 2021

Active surveillance in males with low- to intermediate-risk localized prostate cancer: A modern prospective cohort study.

Investig Clin Urol 2021 07;62(4):416-422

Department of Urology, University Hospital CHUV, Lausanne, Switzerland.

Purpose: To compare the clinical outcome of males with low-risk and favorable intermediate-risk prostate cancer managed within a standardized modern protocol of active surveillance.

Materials And Methods: This was a prospective cohort study with strict and expanded active surveillance criteria in males with prostate cancer. Baseline assessment included multiparametric magnetic resonance imaging (mpMRI), extended systematic biopsy, and software-based MR-targeted biopsy. Follow-up included biannual prostate-specific antigen (PSA) check, mpMRI, and control biopsy once a year for the first 2 years, and afterward mpMRI every 2 years with additional tests as clinically indicated. The primary outcome was the transition rate to active treatment.

Results: A total of 51 patients were included: 17 (33%) and 34 (67%) followed protocols of strict (study arm 1) and expanded (study arm 2) active surveillance criteria, respectively. Median age and PSA were 65 years (IQR, 60-69 years) and 5.3 ng/mL (IQR, 4.5-7.7 ng/mL), respectively. At baseline, a median of 2 (IQR, 1-3) cores were positive out of 13 (IQR, 12-14) cores; 22 males (43%) had visible mpMRI lesions. Eight males (24%) in study arm 2 had Gleason score 3+4. After a median follow-up of 36 months (IQR, 24-48 mo), no patient in study arm 1 compared with 17 patients (33%) in arm 2 underwent active treatment (p<0.0005).

Conclusions: Although expanding eligibility criteria leads to a greater transition rate to active treatment, active surveillance should be contemplated in well-selected males with favorable intermediate-risk prostate cancer as the curability window seems to be maintained.
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http://dx.doi.org/10.4111/icu.20200601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246019PMC
July 2021

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

Eur Urol Focus 2021 Jun 16. Epub 2021 Jun 16.

Department of Urology, Urology Research Unit, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Electronic address:

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. S2L, S3L, and S6L were not expressed, and few bladder tumor cell lines expressed S5L and S14L. In contrast, S7L and S10L were upregulated on all bladder tumor cell lines. We found a discrepency in S9L expression by nontumor cell lines, which is however highly expressed by bladder tumor cell lines. Notably, expression of S5L, S6L, and S14L was increased upon bacillus Calmette-Guérin (BCG) infection. Furthermore, we analyzed the expression of Siglecs on T cells from healthy donors and BCa patients. Circulating T cells only expressed Siglec-6, which is upregulated in non-muscle-invasive BCa patients. In addition, BCG therapy induced the overexpression of Siglec-6 by urinary CD8 T cells. In vitro functional assays suggested that Siglecs may decrease cytotoxic functions of effector CD8 T cells. Finally, analyses from two BCa datasets (The Cancer Genome Atlas and UROMOL cohorts) showed that Siglec-6 is associated with tumor progression and poor survival. Our findings indicate that Siglec-6 might be a new target for BCa treatments. PATIENT SUMMARY: We investigated the expression of Siglecs, a family of immunoregulatory receptors, in bladder cancer patients. We observed that the expression of Siglec-6 is increased on circulating and urinary T cells of non-muscle-invasive bladder cancer patients. We also showed that Siglec-6 is associated with lower survival in bladder cancer patients and might contribute to bladder cancer recurrence.
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http://dx.doi.org/10.1016/j.euf.2021.06.001DOI Listing
June 2021

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

Urol Oncol 2021 05 17;39(5):297.e9-297.e16. Epub 2020 Dec 17.

Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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. Patient's characteristics, mpMRI findings, biopsy technique, and histopathological results were extracted. The primary outcome was to determine the detection rate of csCaP, defined as any Gleason pattern ≥ 4. A multivariable analysis was performed to identify predictors of positive findings at IB.

Results: Fifty-three men were included. Median age was 68 years (interquartile range [IQR] 64-68), median Prostate-Specific Antigen (PSA) was 7.6 ng/ml (IQR 5.2-10.9), and median prostate volume was 59 ml (IQR 44-84). Fifty-six lesions with PIRADS score 3 in 9 cases (16%), 4 in 30 cases (54%), and 5 in 17 cases (30%) were detected. FTB was performed in all cases using a transrectal approach with 3 different platforms (Toshiba, Koelis, and Artemis). Median time between FTB and IB was 3 months (IQR 1-7). A median of 2 cores per lesion were collected with IB (IQR 2-3). No cancer, clinically insignificant and clinically significant cancer were found in 33 (59%), 9 (16%), and 14 (25%) targeted lesions, respectively. Median maximum cancer core length and maximum positive percentage were 9 mm (3-13) and 55% (21%-80%). The only predictor of csCaP on IB was prostate volume (P = 0.026) with an ideal cut-off at 70 ml.

Conclusion: One in 4 patients with previous negative FTB, IB was able to detect csCaP. According to this study, IB would be of particularly useful in patients with large glands.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.041DOI Listing
May 2021

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

Eur J Cancer 2020 08 23;135:173-182. Epub 2020 Jun 23.

Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. Electronic address:

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. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC).

Patients And Methods: Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets.

Results: In both patient groups, the frequency of total CD141 DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141 DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival.

Conclusions: cDC1s are reduced in patients with OvC, and CD141 DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141 DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC.
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http://dx.doi.org/10.1016/j.ejca.2020.04.036DOI Listing
August 2020

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

Urol Oncol 2020 11 10;38(11):846.e1-846.e7. Epub 2020 Jun 10.

Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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. The aim of this study was to assess the value of CEUS immediately after focal HIFU.

Materials And Methods: Retrospective analysis of a prospectively maintained registry including consecutive men undergoing focal HIFU (Focal One). Candidates for focal HIFU were treatment naive men with ≥10 years life expectancy, prostate-specific antigen (PSA) ≤ 20 ng/ml, TNM primary tumor, regional lymph nodes, distant metastasis stage ≤ T2c N0 M0 with a multiparametric MRI (mpMRI) visible lesion concordant with histologically proven prostate cancer. CEUS evaluation was performed immediately at the end of the procedure. Based on the surgeon's estimation of CEUS imaging, re-HIFU was performed, followed by another CEUS evaluation. To test our hypothesis, the results of the CEUS were compared to the results of early mpMRI to rule out clinically significant cancer. The concordance between the 2 tests was measured using the Cohen's kappa. The best model including relevant predictors was calculated with CEUS or with mpMRI to determine their respective added value.

Results: Of 66 men who underwent HIFU, 32 met eligibility criteria. Bifocal treatment was performed in 1 man, increasing the number of treated lesions to 33. Further ablation based on CEUS was delivered intraoperatively to 13 lesions (39%). The positive biopsy rate for clinically significant cancer in the treated zones was 30% (10/33). The negative predictive value of CEUS and early mpMRI was 71% (95% confidence interval: 59%-82%). Concordance between CEUS and mpMRI was significant with a 72.7% agreement (P = 0.001). The model with CEUS showed the best accuracy with an area under the curve of 0.881.

Conclusion: CEUS has a higher added value compared to early mpMRI in ruling out clinically significant cancer after focal HIFU. It should be evaluated whether the use of CEUS intraoperatively enhances the efficacy of focal HIFU.
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http://dx.doi.org/10.1016/j.urolonc.2020.05.010DOI Listing
November 2020

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

Rev Med Suisse 2019 Nov;15(673):2195-2197

Service d'urologie, CHUV, 1011 Lausanne.

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. Patients' selection remains a crucial step to define the best treatment. This article summarizes the new tendencies of urologic cancer management in elderly patients.
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November 2019

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

Rev Med Suisse 2019 Nov;15(673):2186-2189

Département des services de chirurgie et anesthésiologie (DSCA), CHUV, 1011 Lausanne.

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.
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November 2019

Coût de la prise en charge du cancer : l’investissement en urologie est-il raisonnable ?

Rev Med Suisse 2019 Nov;15(673):2183-2184

Médecin-chef, Service d'urologie, CHUV, Lausanne.

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November 2019

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

J Immunother Cancer 2019 10 10;7(1):257. Epub 2019 Oct 10.

Department of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

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.

Methods: CD8 T cell cytokine production following stimulation was quantified by intracellular staining and flow cytometry. The cytotoxic capacity of tumor infiltrating lymphocytes (TILs) was quantified by the chromium release assay following co-culture with autologous or anti-CD3-loaded tumor cell lines. The CD8 T cell metabolic fitness was evaluated by the seahorse assay and by the quantification of 2-NBDG uptake and CD71/CD98 upregulation upon stimulation. The expression of AdoRs was assessed by RNA flow cytometry, a recently developed technology that we validated by semiquantitative RT-PCR (qRT-PCR), while the impact on T cell function was evaluated by the use of selective antagonists and agonists. The influence of Ado/AdoR on the PKA and mTOR pathways was evaluated by phosphoflow staining of p-CREB and p-S6, respectively, and validated by western blot.

Results: Here, we demonstrate that Ado signaling through the A2A receptor (A2AR) in human peripheral CD8 T cells and TILs is responsible for the higher sensitivity to Ado-mediated suppression of T central memory cells. We confirmed that Ado is able to impair peripheral and tumor-expanded T cell effector functions, and we show for the first time its impact on metabolic fitness. The Ado-mediated immunosuppressive effects are mediated by increased PKA activation that results in impairment of the mTORC1 pathway.

Conclusions: Our findings unveil A2AR/PKA/mTORC1 as the main Ado signaling pathway impairing the immune competence of peripheral T cells and TILs. Thus, p-CREB and p-S6 may represent useful pharmacodynamic and efficacy biomarkers of immunotherapies targeting Ado. The effect of Ado on T cell metabolic fitness reinforces the importance of the adenosinergic pathway as a target for next-generation immunotherapy.
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http://dx.doi.org/10.1186/s40425-019-0719-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788118PMC
October 2019

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

Urol Int 2019 10;103(3):357-363. Epub 2019 Sep 10.

Department of Urology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

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. Data was analyzed using descriptive statistics and chi-square tests to determine differences between frequencies of answers.

Results: Hundred and five members of Swiss Urology (38%) completed the survey. All treatment modalities are available for the majority of respondents. Ureterorenoscopy was found to have the highest availability (100%) and was the preferred choice in the majority of stone scenarios. A high adherence to the guidelines was found for the treatment of ureteral stones <10 mm (100% proximal and distal), and >10 mm (69% proximal, 94% distal). All respondents answered in accordance with the guidelines regarding the treatment of middle and upper pole stones <10 mm, 10-20 mm and lower pole stones 10-20 mm. Guideline adherence was 99% for lower pole stones <10 mm, 78% for lower pole stones >20 mm, and 63% for middle/upper pole stones >20 mm.

Conclusion: This survey provides a detailed insight into current stone treatment practices in Switzerland. The full spectrum of urinary stone treatment options is available for the majority of Swiss urologists. The choice of treatment shows a high accordance with evidence-based guidelines and a preference for retrograde endoscopic surgery in the majority of stone scenarios.
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http://dx.doi.org/10.1159/000502806DOI Listing
February 2020

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

Front Immunol 2019 29;10:622. Epub 2019 Mar 29.

Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

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. Here, we quantified and phenotypically/functionally characterized DP T cells in blood from urological cancer patients. We analyzed blood leukocytes of 24 healthy donors (HD) and 114 patients with urological cancers, including bladder ( = 54), prostate ( = 31), and kidney ( = 29) cancer patients using 10-color flow cytometry. As compared to HD, levels of circulating DP T cells were elevated in all urological cancer patients, which could be attributed to increased frequencies of both CD4CD8 and CD4CD8 DP T-cell subsets. Of note, most CD4CD8 DP T cells show a CD8αα phenotype, whereas CD4CD8 cells express both CD8α and CD8β subunits. Functional properties were investigated using generated DP T-cell clones. DP T cells from patients were skewed toward an effector memory phenotype, along with enhanced Th2 cytokine production. Interestingly, both CD8αα and CD8αβ DP T cells were able to trigger Th2 polarization of naïve CD4 T cells, while restraining Th1 induction. Thus, these data highlight a previously unrecognized immunoregulatory mechanism involving DP CD4CD8 T cells in urological cancers.
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http://dx.doi.org/10.3389/fimmu.2019.00622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450069PMC
August 2020

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

Cancer Immunol Res 2019 04 29;7(4):621-629. Epub 2019 Jan 29.

Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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. By IHC and morphology, both BCG and Ty21a instillations were associated with bladder inflammation, which was decreased with the use of low, but effective doses of Ty21a. Flow-cytometry analysis showed a significant infiltration of T cells, natural killer (NK) cells, and myeloid cells, compared with controls, after a single dose of Ty21a, whereas this was only observed after multiple doses of BCG. The induced myeloid cells were predominantly neutrophils and Ly6CCD103 dendritic cells (DC), the latter being significantly more numerous after instillation of Ty21a than BCG. infection of human leukocytes with Ty21a, but not BCG, similarly significantly increased DC frequency. CD4 and CD8 T cells, but not NK cells nor neutrophils, were required for effective bladder tumor regression upon Ty21a treatment. Thus, the generation of antitumor adaptive immunity was identified as a key process underlying Ty21a-mediated treatment efficacy. Altogether, these results demonstrate mechanisms behind intravesical Ty21a therapy and suggest its potential as a safe and effective treatment for NMIBC patients.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0671DOI Listing
April 2019

[Urology in 2018].

Rev Med Suisse 2019 Jan;15(634):167-169

Service d'urologie, CHUV, 1011 Lausanne.

This article summarizes the milestones in urology in 2018 in the following areas : urinary tract infection, functional bladder disorders, oncology and renal colic treatment.
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January 2019

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

Int J Qual Health Care 2019 Dec;31(10):787-792

Urology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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.

Implementation And Evaluation: The study started on January 2015 and ended up on March 2016, involving 908 and 616 DL for old and new process, respectively. The new process decreased the average delay of DL completion from 24.88 days to 14.7 days. Standard deviation of total average delay for DL completion fell from 10.1 days to 7.5 days. We identified four steps needed to DL creation and allowed maximum 2 days for every step completion. No additional resources were employed.

Lessons Learned: We were able to improve the process of DL creation, by analysing its steps and reducing their variability. This can be easily transposed to other medical departments.
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http://dx.doi.org/10.1093/intqhc/mzy253DOI Listing
December 2019

[Ambulatory surgery in urology].

Rev Med Suisse 2018 Nov;14(629):2164-2166

Service d'urologie, CHUV, 1011 Lausanne.

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. Additionally, it is essential to lower the burden of healthcare systems financially, without compromising quality of care. Ambulatory surgery needs a multidisciplinary team involvement, where the general practitioner has a key role.
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November 2018

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

Rev Med Suisse 2018 Nov;14(629):2150-2153

Service d'urologie, CHUV, 1011 Lausanne.

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.
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November 2018

Changement de pratique en urologie et dans le monde de la santé : les bienfaits de la prise de recul.

Rev Med Suisse 2018 Nov;14(629):2147-2148

Service d'urologie, HUG, Genève.

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November 2018

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

Int J Radiat Oncol Biol Phys 2019 02 27;103(2):320-334. Epub 2018 Sep 27.

Department of Oncology, Radiation Oncology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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.

Patients And Methods: Patients with localized PCa were treated with stereotactic extreme hypofractionated doses of 36.25 Gy in 5 fractions to the whole prostate while simultaneously escalating doses to the magnetic resonance image-visible DIN (45 Gy, 47.5 Gy, and 50 Gy in 5 fractions). The phase 1a part was designed to determine the recommended phase 1b dose in a "3 + 3" cohort-based, dose-escalation design. The primary endpoint was dose-limiting toxicities defined as ≥grade 3 gastrointestinal (GI) or genitourinary (GU) toxicity (or both) by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) up to 90 days after the first radiation fraction. The secondary endpoints were prostate-specific antigen kinetics, quality of life (QoL), and blood immunologic responses.

Results: Nine patients were treated in phase 1a. No dose-limiting toxicities were observed at either level, and therefore the maximum tolerated dose was not reached. Further characterization of tolerability, efficacy, and immunologic outcomes was conducted in the subsequent 11 patients irradiated at the highest dose level (50 Gy) in the phase 1b expansion cohort. Toxicity was 45% and 25% for grades 1 and 2 GU, and 20% and 5% for grades 1 and 2 GI, respectively. No grade 3 or worse toxicity was reported. The average (±standard error of the mean) of the QoL assessments at baseline and at 3-month posttreatment were 0.8 (±0.8) and 3.5 (±1.5) for the bowel (mean difference, 2.7; 95% confidence interval, 0.1-5), and 6.4 (±0.8) and 7.27 (±0.9) for the International Prostate Symptom Score (mean difference, 0.87; 95% confidence interval, 0.3-1.9), respectively. A subset of patients developed antigen-specific immune responses against prostate-specific membrane antigen (n = 2), prostatic acid phosphatase (n = 1), prostate stem cell antigen (n = 4), and prostate-specific antigen (n = 2).

Conclusions: Irradiation of the whole prostate with 36.25 Gy in 5 fractions and dose escalation to 50 Gy to the DIN was tolerable and determined as the recommended phase 1b dose. This treatment has promising antitumor activity, which will be confirmed by the ongoing phase 2 part. Preliminary QoL analysis showed minimal impact in GU, GI, and sexual domains. Stereotactic irradiation induced antigen-specific immune responses in a subset of patients.
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http://dx.doi.org/10.1016/j.ijrobp.2018.09.023DOI Listing
February 2019

Intramuscular Immunization Induces Antigen-specific Antibodies in Urine.

Eur Urol Focus 2020 03 13;6(2):280-283. Epub 2018 Sep 13.

Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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. As a model antigen/vaccine, levels of total and vaccine-specific antibodies were determined in urine as a spin-out study of a phase 1 trial. Non-muscle-invasive bladder cancer (NMIBC) patients at different risks of progression, undergoing intravesical bacillus Calmette-Guérin (BCG) immunotherapy or not, received an adjuvanted recombinant protein vaccine that resulted in high titers of vaccine-specific serum immunoglobulin G (IgG) in all patients, regardless of the risk group. Vaccine-specific IgG and immunoglobulin A (IgA) were detected in urine of half of the patients at low risk of progression NMIBC and in all the intermediary/high- (int/high) risk patients. Vaccine-specific IgG titers were correlated to total urinary IgG levels, the latter being higher in the int/high-risk patients. In contrast, vaccine-specific IgA did not correlate to urinary IgA levels. Furthermore, vaccine-specific antibodies were transiently increased by intravesical BCG instillations. Altogether, our data show that a standard i.m. immunization can effectively induce antigen-specific antibodies in urine, which, upon selection of optimal vaccine targets, may provide protection against UTI. Vaccine-specific IgG titers were dependent on conditions affecting total urinary IgG levels, while production of vaccine-specific IgA in situ might independently contribute to protection against infections in the bladder. PATIENT SUMMARY: Towards the development of vaccines able to protect against urinary tract infections, we examined the potential of the intramuscular vaccination using a model antigen. We found two types of specific antibodies in the urine, which together may locally contribute to protection against infections, thus supporting the use of such a standard immunization route.
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http://dx.doi.org/10.1016/j.euf.2018.09.003DOI Listing
March 2020

Conventional and PD-L1-expressing Regulatory T Cells are Enriched During BCG Therapy and may Limit its Efficacy.

Eur Urol 2018 11 19;74(5):540-544. Epub 2018 Jul 19.

Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address:

The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment. Immunoregulatory mechanisms have emerged as key players in various cancers. While T lymphocytes are crucial for the control of tumor growth, they often include regulatory subsets known to restrain their anti-tumor activity. In this prospective study, we assessed conventional regulatory T cells (cTregs) and PD-L1-expressing CD4 T cells (PD-L1 Tregs) levels in blood and urine of urothelial cancer (UCa) patients undergoing BCG treatment. Local cTregs were found at higher frequencies than their counterpart in the periphery and induced by bladder tumor cells in vitro. Interestingly, while circulating PD-L1 Tregs were hardly detectable in the blood of healthy donors and UCa patients, substantial levels were found in patients' urine. In vitro experiments suggested that BCG infection of urothelial cells could induce PD-L1 Tregs, partially via an interferon-β-mediated mechanism. Of note, high level of Tregs in urine was associated with rapid recurrence following BCG therapy. Our findings demonstrate that T lymphocytes recruited during BCG therapy encompass a significant fraction of regulatory cells including a non-classical source of PD-L1 and reinforce treatment strategies combining BCG with PD-1/PD-L1 checkpoint inhibitors as promising approaches for non-muscle invasive bladder cancer.

Patient Summary: We investigated the presence of particular immune cell types in the urine of bladder cancer patients undergoing Bacillus Calmette-Guerin (BCG) therapy. We identified a cell type that is strongly enriched in the urine after BCG instillation and that may favor tumor recurrence. This immune subpopulation might be targeted for bladder cancer treatment.
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http://dx.doi.org/10.1016/j.eururo.2018.06.045DOI Listing
November 2018

[Urology].

Rev Med Suisse 2018 Jan;14(588-589):97-99

Service d'urologie, CHUV, 1011 Lausanne.

This article points at recent developments in urology in the field of malignant diseases of the urinary system and the diagnostic and therapeutic management of benign conditions as well, that occur frequently in our ageing population.
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January 2018

[Local treatment in oligometastatic urological malignancies : evidence of wishful thinking ?]

Rev Med Suisse 2017 Nov;13(585):2083-2086

Service d'urologie, CHUV, 1011 Lausanne.

In the past, it was generally considered that the window of curability had been missed in metastatic solid cancers. At present, novel evidence suggests that oligometastatic cancer might be amenable to a multimodal curative treatment, including ablation of the primary tumour. In this article, we summarise the indications, the controversies and future perspectives of local treatment in oligometastatic urological malignancies.
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November 2017

[Immunotherapy : a revolution in the management of urothelial bladder cancer ?]

Rev Med Suisse 2017 Nov;13(585):2074-2078

Département d'urologie, CHUV, 1011 Lausanne.

The treatment of urothelial bladder cancer has changed very little in recent years, with high rates of disease recurrence and progression, even in low aggressive urothelial bladder cancer. Immunotherapy has already proven its effectiveness as a treatment for several types of cancer and has been used in high-grade non-muscle-invasive bladder cancer for decades. Recent findings on immune checkpoints inhibitors have opened up a new chapter for treatment of bladder cancer, offering interesting therapeutic perspectives that could revolutionize the management.
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November 2017

Urologie évolutive : par X, Y et Z… et encore !

Rev Med Suisse 2017 Nov;13(585):2067

Service d'urologie, CHUV, Lausanne.

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November 2017

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect.

Urol Int 2017 9;99(3):358-366. Epub 2017 Aug 9.

Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Objective: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance.

Patients And Methods: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate.

Results: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015).

Conclusion: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.
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http://dx.doi.org/10.1159/000477973DOI Listing
June 2018

[Urology : therapeutics news in 2016].

Rev Med Suisse 2017 Jan;13(544-545):110-111

Service d'urologie, CHUV, 1011 Lausanne.

This article summarizes recent advances in the field of urinary infections, bladder function, minimal invasive surgery and genitourinary cancers.
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January 2017

[Management of genitourinary trauma].

Rev Med Suisse 2016 Nov;12(541):2072-2076

Service d'urologie, CHUV, 1011 Lausanne.

Urogenital trauma often occurs in the context of polytrauma patients. In this article, aimed at primary care practitioners and emergency physicians, we summarise the epidemiology and aetiology of these traumas as well as their management. The goal is to allow primary healthcare professionals to become acquainted with diagnostic and therapeutic strategies in genitourinary trauma patients.
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November 2016

[Common medications and prostate cancer : what is the association ?]

Rev Med Suisse 2016 Nov;12(541):2068-2071

Service d'oncologie, CHUV, 1011 Lausanne.

A possible association between prostate cancer and metabolic syndrome has recently been observed. Further, multiple experimental and epidemiologic studies have recently reported a probable association between common medications and prostate cancer. In this article, we summarize the results of those studies that explore the role of aspirin, oral antidiabetic medication and statins.
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November 2016

[Assessment and treatment of genitourinary infections].

Rev Med Suisse 2016 Nov;12(541):2054-2059

Service d'urologie, CHUV, 1011 Lausanne.

Antibiotics are most commonly prescribed for urinary bacterial infections. The purpose of this article is to review the most common infections of the genitourinary tract and to guide the choice of the most appropriate treatment. This choice depends also on the patients general state, local associated conditions and can range from observation to an emergency hospitalisation. Primary care physicians remain in the first line to take care of these patients but the urologists or the infectious disease specialists can provide some help in complex situations.
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November 2016
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