[Profile and immune environment of upper tract urothelial carcinoma]. / Profil et environnement immunitaires des tumeurs de la voie excrétrice supérieure.

INTRODUCTION AND OBJECTIVES: Upper Tract Urothelial Carcinoma (UTUC) are tumors that share similarities with bladder tumors. Immunotherapy is already used for bladder locations and appears to have interest for UTUC. In order to rationalize the immunotherapy development pipeline it seemed necessary to describe the immune infiltrate of a cohort of UTUC treated with nephroureterectomy and to determine the expression of a panel of immune checkpoints and co-stimulatory molecules on tumor cells as well as on infiltrating and circulating lymphocytes. MATERIALS AND METHODS: This is a monocentric, prospective and exploratory work. Patients treated with total nephroureterectomy or segmental ureterectomy for presumably infiltrative (≥ T1) UTUC managed at the Saint-Louis Hospital were included from January 2019 to July 2020. A set of markers and immune checkpoints were studied by flow fluorocytometry on circulating lymphocytes (PBMCs) and tumor-infiltrating lymphocytes (TILs). Some markers were also studied by immunohistochemistry on tumor sample. RESULTS: In total, 14 patients were included and 13 patients could be analyzed. 1 patient had no residual tumor. 5 tumors out of the 12 (41.7%) showed a lymphocytic inflammatory infiltrate. PD1 was the most represented checkpoint with a median expression rate of 41.4% on CD4+ TILs and 3.89% on circulating CD4+ T cells. This rate was 62.4% and 7.45% respectively on CD8+ T cells. TIGIT was the second most represented marker with a median expression rate on tumor-infiltrating CD4+ T cells of 25% and 2.9% on circulating CD4+ T cells. The median expression level of TIGIT on tumor-infiltrating CD8+ T cells was 23.3% and 3.2% on circulating CD8+ T cells. ICOS was highly expressed on CD4+ TILS with a median of 33.9% in contrast to CD8+ TILS (median: 6.67%). Variable expression of other checkpoints (ILT2, TIM3, LAG3 and OX40) was found without clear trend. CONCLUSION: This exploratory work highlighted that PD1 was the most represented checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 and LAG3 were 3 other checkpoints whose expression was found to be less important. ILT2 and OX40 appeared to be weakly expressed. LEVEL OF EVIDENCE: II.

[Active surveillance of prostate cancer: treatement-free survival according to restricted or expanded eligibility criteria]. / Surveillance active du cancer de prostate : survie sans traitement curatif selon critères d'éligibilité stricts ou élargis.

AIM: Overtreatment is an actual problem in low risk localized prostate cancer (PC) management. Active surveillance (AS) is a solution to limit this problem, but eligibility criteria remained discussed. The aim was to assess possibilities of widening selection criteria for patient in AS, studying curative treatment free survival (CTFS) according to restricted or expanded eligibility criteria. METHODS: We retrospectively studied patients beginning AS between 2008 and 2014, for Gleason 6 localized PC, PSA<15ng/ml,

Metastatic Renal Cell Carcinoma in a Renal Allograft: A Sustained Complete Remission After Stimulated Rejection.

We report the case of a 40-year-old woman who recovered from a diffuse metastatic renal cell carcinoma that developed from a kidney allograft. She was successfully treated by the induction of tumor rejection. Immunosuppression was discontinued, and transplant nephrectomy was deliberately delayed based on the expectation that the tumor mass would trigger the alloimmune response, which was stimulated with pegylated interferon-α-2a. Three years later, the patient remained in complete remission. Despite this severe context, the present case shows that the poor prognosis of allograft metastatic renal cell carcinoma could be dramatically reversed by taking advantage of the donor tumor origin to actively induce a specific alloimmune rejection of the tumor.

C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR.

[Henoch-Schönlein purpura in the adult]. / Purpura rhumatoïde de l'adulte.

Henoch-Schönlein purpura is a systemic vasculitis of the small vessels characterized by perivascular leucocyte infiltrates. It is an immunoglobulin A-related immune complex-mediated disease involving the skin, the joints and the gastrointestinal system. Renal disease may sometimes be associated to these clinical manifestations. Prevalence of the nephritis is highly variable, depending on the series. More rarely, other organs such as the lungs, the heart or the nervous system may be involved. The clinical diagnosis is confirmed by histopathology of the skin (leukocytoclastic vasculitis) and kidney (endo-capillary proliferative glomerulonephritis), showing IgA deposits in these tissues. Short-term prognosis depends on the severity of digestive involvement, but long-term prognosis depends on the renal disease. Recent publications of pediatric and adult series show that the chronic renal failure may progress, sometimes more than ten years after the initial flare. Treatment is usually supportive. The benefit of more specific treatments (corticosteroids or immunosuppressive drugs) in severe visceral forms (usually abdominal or kidney) has not yet been established.

[Guidelines from the Infectious Disease Committee of the French Association of Urology and The Neuro-Urology Committee of the AFU: antibiotic prophylaxis for sacral neuromodulation]. / Recommandations de bonnes pratiques cliniques : antibioprophylaxie et neuromodulation des racines sacrées par le Comité d'infectiologie de l'Association française d'urologie (CIAFU) et le Comité de neuro-urologie de l'AFU.

INTRODUCTION: In urology, antibiotic prophylaxis is advised by the French Association of anesthesiology (SFAR) and the Infectious Disease Committee of the French Association of urology guidelines published in 2010. No guideline exists concerning the implantation of neuromodulation implants. MATERIAL AND METHOD: A literature analysis was performed on sacral modulation and antibiotic prophylaxis. Then guidelines were discussed by reviewers. Items that showed no consensus were then discussed again to arrive at recommendations. RESULTS: Antibiotic prophylaxis is recommended during the test phase as well as in the case of installation of sacral neuromodulation (Grade C). Antibiotic recommended (Grade B) are: cefotetan or cefoxitin, 2g dose by slow intravenous injection or amoxicillin-clavulanic acid at a dose of 2 g, intravenously or, in the case of allergy vancomycin at a dose of 15 mg/kg or the clindamycin has 600 mg intravenously. CONCLUSIONS: Despite the lack of high level of evidence, antibiotic prophylaxis seems necessary when setting up of electrode case of sacral neuromodulation.

Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence.

Papillary renal-cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY-FISH in sex-mismatched kidney transplants, and polymorphic microsatellite DNA and high-resolution melting of mitochondrial DNA analyzes in all five patients on laser-microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal-cell carcinoma.

[Flexible cystoscopes: disinfection and microbiological surveillance practices among French urologists]. / Cystoscopes souples : pratiques de désinfection et de surveillance microbiologique parmi les urologues français. Une enquête du comité d'infectiologie de l'AFU.

INTRODUCTION: According to the French regulatory authorities, the highest level of disinfection must be achieved for flexible cystoscopes, as they enter a sterile cavity, the current method being peracetic acid disinfection and sterile water terminal rinsing. MATERIAL AND METHODS: The concordance between regulations and the routine was researched using a self-administered questionnaire sent to all French urologists. RESULTS: Responses from 78 urology units, totalling 317 urologists (26% response rate) were analysed. As a whole, 51.2% of centers followed all recommendations on disinfection. There was no microbiological surveillance in 16.6% of centers, although microbiological tests were performed in two out of three centers before using a new endoscope or when returning from maintenance. CONCLUSION: Improvements are needed, both in the disinfection process and the microbiological surveillance. Low temperature sterilization and the use of sterile disposable sheaths may represent an alternative.

Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection.

Different strategies appear to improve the success in treatment of antibody-mediated rejection (AMR), although no one best method has yet emerged. The objective of this study was to compare the efficacy of the combination of Plasmapheresis/intravenous immunoglobulin (IVIg)/anti-CD20-based regimes versus high-dose IVIg alone in the treatment of AMR. Group A (12 patients) was treated with high-dose IVIg between January 2000 and December 2003; group B (12 patients) was treated by Plasmapheresis/IVIg/anti-CD20 between January 2004 and December 2005. Graft survival at 36 months was 91.7% in group B versus 50% in group A (p = 0.02). Donor-specific human leukocyte antigens (DSA) levels detected by Luminex single antigen (Luminex SA) and ELISA, 3 months postrejection are significantly lower in group B than in group A: DSA ELISA class 2 score 6-8 (p = 0.02), DSA mean intensity of fluorescence (MFI) max (p = 0.009) and DSA mean MFI (p = 0.0004). The persistence of elevated DSA levels posttreatment is more frequent in patients with graft loss as compared to those with preserved renal function: score 6-8 on ELISA (p = 0.04); mean MFI (p = 0.00009) and MFImax (p = 0.018). We conclude that: (1) high dose IVIg alone is inferior to Plasmapheresis/IVIg/anti-CD20 as therapy for AMR and (2)DSA postrejection can be quantified using solid phase assays, showing that 3 months after AMR, DSA levels are higher in patients with graft loss.

Nephron sparing surgery is a feasible and efficient treatment of T1a renal cell carcinoma in kidney transplant: a prospective series from a single center.

PURPOSE: Renal cell carcinoma in a renal graft is a rare condition whose incidence will increase in the future. To our knowledge no standardized treatment has been established for this disease. We performed a prospective study of nephron sparing surgery for small renal cell carcinoma in renal grafts. MATERIALS AND METHODS: From January 2002 to December 2006, 2,050 renal graft recipients were followed at our transplantation center. Of these patients 7 were diagnosed with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom presented with T1a renal cell carcinoma and prospectively underwent nephron sparing surgery. RESULTS: Five patients with 15 to 30 mm (median 20) renal cell carcinoma were included in the study and were treated with nephron sparing surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No postoperative complications were observed (hemorrhage, urinary fistulas, renal failure). Preoperative immunosuppressive treatment was not modified postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4 months of followup (range 5 to 54) no significant impairment of renal function or recurrence was observed. CONCLUSIONS: Nephron sparing surgery is a safe and efficient procedure for the treatment of renal cell carcinoma in renal grafts, resulting in the preservation of renal function and in short-term cancer control.

Risk factors for early epithelial to mesenchymal transition in renal grafts.

Epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs) may participate in the pathogenesis of renal fibrosis. We performed a prospective study of EMT markers in protocol biopsies obtained 3 months after engraftment from 56 patients who received deceased donor kidneys and who had stable renal function. The presence of EMT was examined, and quantified by immunohistochemical staining for vimentin and translocation of beta-catenin to the cytoplasm. EMT status was defined as the presence of EMT markers in > or = 10% of TECs. EMT features were virtually absent in implantation biopsies, whereas 41% of the grafts were EMT-positive in the absence of advanced chronic allograft nephropathy. Thirteen patients (23%) had borderline changes or acute rejection. EMT features were more frequent in these patients than in those with normal kidney grafts (vimentin expression, p = 0.003; beta-catenin translocation, p = 0.002). EMT in grafts corresponded with elevated serum creatinine of the donor before the recovery of kidney (p = 0.02) and longer cold ischemia time (p = 0.02). In contrast, the donor age had no influence on the expression of EMT markers. These results suggest that EMT is an early and frequent phenomenon in kidney transplants that could be triggered by immunological and/or ischemic tubular injury.

[The value of preoperative perineal rehabilitation in radical prostatectomy and replacement entero-cystoplasty. Preliminary results]. / Intérêt de la rééducation périnéale pré-opératoire dans les prostatectomies radicales et les entérocystoplasties de remplacement. Résultats préliminaires.

Radical surgery of the prostate and replacement entero-cystoplasty are associated with varying degrees of risk of diurnal or nocturnal incontinence, which is always poorly tolerated by the patient. In order to reduce this discomfort, perineal reeducation, commenced before the operation, appears to be a valuable aid. A survey of sphincter function easily detects patients at risk and postoperative sphincter disorders can be prevented to a large degree. The authors analyse their preliminary results in 14 patients undergoing radical prostatectomy and in another 10 patients undergoing replacement entero-cystoplasty.

[Prognostic value of cytofluorometry in bladder tumors]. / Intérêt pronostique de la cytofluorométrie dans les tumeurs vésicales.

Bladder lavage fluid was examined using flow-cytometry (FCM) in 112 patients with transitional cell carcinoma seen over 30 months. FCM investigates the entire mucosa, furnishes indications as to the possible existence of dysplasia or carcinoma in situ, and thus provides for a more accurate evaluation of the evolutive potential of the "bladder disease". FCM consists in the automated assay of the DNA content of epithelial cells. The test is positive when "tumorous" diploid or aneuploid cells are demonstrated. The diagnostic sensitivity of FCM is comparable to that of cytologic diagnosis on bladder lavage specimens, but FCM has the additional advantage of detecting those patients at high risk for disease progression by measurement of the DNA index. Grade 1 and 2 tumors are diploid in 70% of patients, against only 14% for grade 3 tumors and carcinomas in situ. Follow up of 25 grade 2 patients and determination of the recurrence index clearly establishes the prognostic significance of the degree of tumorous ploidy. Furthermore, the effectiveness of endovesical chemotherapy can be monitored using FCM measurement of the aneuploidy index.

[Spontaneous regression of regressive pulmonary metastases from kidney cancer. Myth or reality? Apropos of 2 cases]. / Régression spontanée de métastases pulmonaires régressives de cancer du rein. Un mythe ou une réalité? A propos de deux cas.

The authors report two cases of regression of lung metastases from renal cell cancer with cytological and histological proof. They present a complete review of the literature and analyse the theories proposed to explain this phenomenon.