[Alteration of pulmonary epithelial permeability by cathepsin S in chronic obstructive pulmonary disease]. / Altération de la perméabilité épithéliale pulmonaire par la cathepsine S au cours de la bronchopneumopathie chronique obstructive.

Smoking is accountable for most of the chronic obstructive pulmonary disease (COPD) cases. COPD, which is characterized by the development of chronic bronchitis, could be associated with emphysema. In active smokers, there is an overexpression of cathepsin S, a cysteine protease, which participates in the development of emphysema via its elastinolytic activity. Likewise, we demonstrated that cathepsin S could degrade one or more protein constituents of cell junctions. This deleterious proteolytic activity leads to an alteration of the integrity of the lung epithelial barrier, which in turn could aggravate chronic inflammation and promote the exacerbation phases associated with infections.

Comparison of open and robotic-assisted partial nephrectomy approaches using multicentric data (UroCCR-47 study).

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35-0.66]; severe: 0.29 [0.16-0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours.

French AFU Cancer Committee Guidelines - Update 2022-2024: management of kidney cancer.

AIM: To update the recommendations for the management of kidney cancers. METHODS: A systematic review of the literature was conducted from 2015 to 2022. The most relevant articles on the diagnosis, classification, surgical treatment, medical treatment and follow-up of kidney cancer were selected and incorporated into the recommendations. Therefore, the recommendations were updated while specifying the level of evidence (high or low). RESULTS: The gold standard for the diagnosis and evaluation of kidney cancer is contrast-enhanced chest and abdominal CT. MRI and contrast-enhanced ultrasound are indicated in special cases. Percutaneous biopsy is recommended in situations where the results will influence the therapeutic decision. Renal tumours should be classified according to the pTNM 2017 classification, the WHO 2022 classification and the ISUP nucleolar grade. Metastatic kidney cancer should be classified according to the IMDC criteria. Partial nephrectomy is the gold standard treatment for T1a tumours and can be performed by an open approach, by laparoscopy or by robot-guidance. Active surveillance of tumours less than 2cm in size can be considered regardless of the patient's age. Ablative therapies and active surveillance are options in elderly patients with comorbidity. T1b tumours should be treated by partial or radical nephrectomy depending on the complexity of the tumour. Radical nephrectomy is the first-line treatment for locally advanced cancers. Adjuvant treatment with pembrolizumab should be considered in patients at intermediate and high risk for recurrence after nephrectomy. In metastatic patients: Immediate cytoreductive nephrectomy may be offered to oligometastatic patients in combination with local treatment of metastases if this can be complete and delayed cytoreductive nephrectomy can be proposed for patients with a complete response or a significant partial response. Medical treatment should be proposed as first-line therapy for patients with a poor or intermediate prognosis. Surgical or local treatment of metastases can be proposed in case of single or oligo-metastases. The recommended first-line drugs for metastatic patients with clear cell renal carcinoma are the combinations axitinib/pembrolizumab, nivolumab/ipililumab, nivolumab/cabozantinib and lenvatinib/pembrolizumab. Cabozantinib is the recommended first-line treatment for patients with metastatic papillary carcinoma. Cystic tumours should be classified according to the Bosniak classification. Surgical removal should be proposed as a priority for Bosniak III and IV lesions. It is recommended that patient monitoring be adapted to the aggressiveness of the tumour. CONCLUSION: These updated recommendations are a reference that will allow French and French-speaking practitioners to improve kidney cancer management.

Incidence and risk factors for urolithiasis recurrence after endourological management of kidney stones: A retrospective single-centre study.

INTRODUCTION: Almost half of the patients have had recurrent nephrolithiasis despite undergoing effective treatment. Our objective is to determine the recurrence rate of lithiasis after endourological management of nephrolithiasis and identify the risk factors for these recurrences. METHODS: Data were gathered retrospectively from all patients who were treated for nephrolithiasis by endourological management from May 2014 to January 2017 in our university hospital. The patients were devised into two groups: with and without recurrence. Many variables were also compared between these two groups. RESULTS: During this period 265 patients were treated for upper urinary tract stone. A total of 190 patients were included in the study. The median age and median BMI of the patients were 57.5 years and 25.2kg/m2, respectively. A biochemical analysis of the stones was performed in 117 (61.5%) patients. The most common types of stones were calcium oxalate monohydrate stones (n=44, 23.2%), mixed stones (n=39, 20.5%) including mixed calcium oxalate (n=10; 8.5%), calcium oxalate dihydrate stones (n=13, 6.8%) and uric acid stones (n=11, 5.8%). At the end of a median follow-up of 32 months (range, 13-61 monthes), 49 patients (25.8%) had a recurrent stone. In univariate analysis, the risk factors for recurrence were BMI greater than 25kg/m2 (HR: 2; P<0.05), diabetes (HR: 3.73; P<0.008) and smoking (HR: 3.1; P<0.039). However age (HR: 0.96: P<0.003) and high blood pressure (HR: 0.37; P<0.027) were protective factors. In multivariate analysis, diabetes, smoking, hypertension, and age are still risk factors for recurrence. CONCLUSION: Stone recurrence is common after the management of urinary stones. In this study 25.8% of patients had recurred stone disease after endourological management with a median follow-up of 32 months. Our study findings showed that diabetes and smoking are risk factors for recurrence, while age and blood hypertension are protective factors that decreased the risk of recurrence.

Off-clamp laparoscopic partial nephrectomy in a hybrid room after tumor embolization versus conventional partial nephrectomy: A propensity score matched pair analysis.

OBJECTIVE: Off-clamp laparoscopic partial nephrectomy in a hybrid operating room after superselective arterial embolization (hLPN) is a promising minimally invasive approach. In this study, we compared the perioperative surgical outcomes of this innovative technique with the conventional standard of care laparoscopic partial nephrectomy (cLPN) technique. PATIENTS AND METHODS: Overall, 86 and 127 patients treated with hLPN and cLPN, respectively, were included. These two techniques were compared in terms of surgical complications, estimated blood loss (EBL), operative time, length of stay (LOS), surgical margins, and Trifecta achievement rate (defined as warm ischemia duration <25 min, negative surgical margins and absence of complications). A propensity score based on age, gender, BMI, preoperative eGFR and tumor size was used for a 1:1 matching of patients of each group. After matching, 2 groups of 67 patients with similar characteristics were obtained. RESULTS: Conversion rate to open surgery, complications and EBL were similar in both groups. Conversely, operative time, LOS and Trifecta rates favored hLPN. The multivariate analysis showed that hLPN had a 70% higher chance of Trifecta achievement than cLPN in all age groups and for all tumor size across the study population. CONCLUSION: Compared to a conventional approach, off-clamp laparoscopic partial nephrectomy in a hybrid room after superselective arterial embolization showed satisfying immediate surgical outcomes and reached a higher rate of Trifecta achievement. Mid and long-term functional and oncological results are needed to establish this minimally invasive surgical alternative.

[Renal cell carcinoma of the kidney transplant: The French guidelines from CTAFU]. / Recommandations françaises du Comité de transplantation de l'association française d'urologie (CTAFU) : Carcinome à cellules rénales du transplant rénal.

OBJECTIVE: To propose recommendations for the management of renal cell carcinomas (RCC) of the renal transplant. METHOD: Following a systematic approach, a review of the literature (Medline) was conducted by the CTAFU to evaluate prevalence, diagnosis and management of RCC arousing in the renal transplant. References were assessed according to a predefined process to propose recommendations with levels of evidence. RESULTS: Renal cell carcinomas of the renal transplant affect approximately 0.2% of recipients. Mostly asymptomatic, these tumors are mainly diagnosed on a routine imaging of the renal transplant. Predominant pathology is clear cell carcinomas but papillary carcinomas are more frequent than in general population (up to 40-50%). RCC of the renal transplant is often localized, of low stage and low grade. According to tumor characteristics and renal function, preferred treatment is radical (transplantectomy) or nephron sparing through partial nephrectomy (open or minimally invasive approach) or thermoablation after percutaneous biopsy. Although no robust data support a switch of immunosuppressive regimen, some authors suggest to favor the use of mTOR inhibitors. CTAFU does not recommend a mandatory waiting time after transplantectomy for RCC in candidates for a subsequent renal tranplantation when tumor stage

[Renal cell carcinoma in candidates for renal transplantation and recipients of a kidney transplant: The French guidelines from CTAFU]. / Recommandations françaises du Comité de transplantation de l'association française d'urologie (CTAFU) : carcinome rénal sur reins natifs chez le patient transplanté rénal ou en attente de transplantation.

OBJECTIVE: To define guidelines for the management of renal cell carcinoma of the native kidney (NKRCC) in kidney transplant (KTx) recipients and renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients candidates for renal transplantation. METHOD: A review of the literature following a systematic approach (Medline) was conducted by the CTAFU to report renal cell carcinoma epidemiology, screening, diagnosis and management in KTx candidates and recipients. References were assessed according to a predefined process to propose recommendations with the corresponding levels of evidence. RESULTS: ESRD patients are at higher risk of RCC with a standardized incidence ratio of approximately 4,5 as compared with general population. NKRCC tumors occur in 1 to 3 % of KTx recipients with a 10 to 15-fold increased risk as compared with general population, especially in patients with acquired multicystic kidney disease. Most authors suggest yearly monitoring of the native kidneys using ultrasound imaging. Radical nephrectomy (either open or laparoscopic approach) is the preferred treatment of NKRCC in KTx recipients and RCC in ESRD. Surveillance in a valid option in small or cystic renal masses. In the localized setting, change in immunosuppressive therapy is not recommended besides perioperative avoidance of mTOR inhibitor to limit morbidity. CTAFU does not recommend a mandatory waiting time after nephrectomy for RCC in ESRD patients candidates for renal tranplantation when tumor stage

Immediate preoperative renal artery embolization in the resection of complex renal tumors (UroCCR-48 Reinbol study).

PURPOSE: We evaluated the feasibility and outcomes of immediate preoperative renal artery embolization (IPRAE) before complex nephrectomy for locally advanced RCC ± inferior vena cava thrombus (IVCT). METHODS: A comparative retrospective (2007-2017) multicenter study which included 145 patients with locally advanced RCC ± IVCT: 99 radical nephrectomies vs. 46 radical nephrectomies with IPRAE identified in the prospective UroCCR national database (CNIL DR 2013-206; NCT03293563). IPRAE was performed under local anesthesia the day of nephrectomy (< 4 h prior to nephrectomy). The primary endpoint was peroperative blood loss (mL). Secondary outcomes were: tolerance of embolization (pain visual scale), success rate of IPRAE defined by complete devascularization of the kidney, perioperative complications according to Clavien score and postoperative GFR. RESULTS: The baseline characteristics of IPRAE and the control groups were similar. Tumor staging was 14% T2b, 41% T3a, 27% T3b, 13% T3c, 6% T4. The success rate of IPRAE was 98%. Median artery embolizated per patient was 2 (Agochukwu and Shuch in World J Urol 32:581-589, 2014; Marshall et al. in J Urol 139:1166-1172, 1988; Yap et al. in BJU Int 110:1283-1288, 2012;Gill et al. in J Urol. 194:929-938, 2015; Wang et al. in Eur Urol 69:1112-1119, 2016). No severe complications occurred after IPRAE. Postembolization syndrome was reported in 7% (Clavien I-II). Mean peroperative blood losses in the IPRAE and control groups were: 726 ± 118 ml and 1083 ± 114 ml (P = 0.03). In a multivariate analysis that included: age, Karnofsky index, IPRAE (yes vs. no), IVCT (yes vs. no), tumor size and synchronous metastasis, no IPRAE and IVCT were significantly associated with increased peroperative bleeding. CONCLUSION: IPRAE before nephrectomy for locally advanced and/or IVCT tumors was well tolerated, was associated with lower peroperative bleeding and did not increase the incidence or severity of postoperative complications.

[French ccAFU guidelines - update 2020-2022: management of kidney cancer]. / Recommandations françaises du Comité de cancérologie de l'AFU ­ actualisation 2020­2022 : prise en charge du cancer du rein.

OBJECTIVE: - To update the French guidelines on kidney cancer. METHODS: - A systematic review of the literature between 2015 and 2020 was performed. The most relevant articles regarding the diagnosis, the classification, surgical treatment, medical treatment and follow-up of kidney cancer were retrieved and included in the new guidelines. The guidelines were updated with corresponding levels of evidence. RESULTS: - Thoraco-abdominal CT scan with injection is the best radiological exam for the diagnosis of kidney cancer. MRI and contrast ultra-sound can be useful in some cases. Percutaneous biopsy is recommended when histological results will affect clinical decision. Renal tumours must be classified according to pTNM 2017 classification and ISUP grade. Metastatic kidney cancers must be classified according to IMDC criteria. Partial nephrectomy is the recommended treatment for T1a tumours and can be done through an open, laparoscopic or robotic access. T1b tumours can be treated by partial or total nephrectomy according to tumour complexity. Radical nephrectomy is the recommended treatment of advanced localized tumours. There is no recommended adjuvant treatment. In metastatic patients: cyto-reductive nephrectomy can be offered in case of good prognosis; medical treatment must be counseled first in case of intermediate or bad prognosis. Surgical or local treatment of metastases should be considered in case of solitary lesion or oligo-metastases. First line recommended drugs in metastatic patients include the associations axitinib/pembrolizumab and nivolumab/ipilimumab. Cystic tumours must be classified according to Bosniak Classification. Surgical excision should be offered to patients with Bosniak III and IV lesions. It is recommended to follow patients clinically and with imaging according to tumour aggressiveness. CONCLUSION: - These updated recommendations should assist French speaking urologists for their management of kidney cancers.

[Prevalence of the tuberous sclerosis complex at patients taken care for a renal angiomyolipoma]. / Prévalence de la sclérose tubéreuse de Bourneville chez des patients pris en charge pour un angiomyolipome rénal.

INTRODUCTION: Bourneville's tuberous sclerosis or Tuberous Sclerosis Complex (TSC) is an autosomal dominant hereditary phakomatosis associated with angiomyolipomas (AML) of the kidney. The aim of this study was to identify the prevalence of TSC in patients diagnosed and cared for AML in our department of urology. MATERIALS AND METHODS: All the patients with AML were included between March 2009 and June 2016 in a French university hospital. Each patient was reviewed in consultation with a clinical examination and imaging. Specific clinical criteria were used to refer patients to genetic analysis. Patients with a high TSC probability had a genetic analysis to search TSC1 and TSC2 genes mutations. RESULTS: In all, 28 patients were included and 3 (11%) were diagnosed TSC. The median age of the patients was 62 years (36-82 years). The most frequent clinical criteria were facial angiofibromas in 7 patients (25%). Among the 8 patients (29%) with evocative clinical criteria, a mutation of the TSC1 and TSC2 genes was identified in 3 patients (11%) with a diagnosis of TSC made before the AML diagnosis. CONCLUSION: In this study, 8 patients (29%) presented clinical criteria suggestive of TSC, preferentially dermatological. The diagnosis was confirmed by screening TSC1 and TSC2 genes mutations in 3 patients (11%), nevertheless prevalence of TSC is most probably underestimated by the genetic mosaïcisme of this pathology.

[Impact of partial nephrectomy in a hybrid operating room on the activity of kidney cancer surgery]. / Évaluation de l'utilisation de la salle hybride sur l'activité de chirurgie en cancérologie rénale.

INTRODUCTION: Partial nephrectomy (NP) after embolization of tumor vessels (NPESH) in a hybrid room combines embolization of tumor vessels and enucleation of the tumor under laparoscopy in the same operative time. The purpose of this study was to assess the impact of the use of NPESH in the management of patients treated with surgery for a localized kidney tumor. MATERIAL AND METHODS: Using the uroCCR database, we included all consecutive patients operated in a university hospital for localized kidney tumor. From 2011 to May 2015, patients were treated by Standard Partial Nephrectomy (NPS) Laparoscopic or Open and from May 2015 to May 2019 by NPESH. We evaluated characteristics of patients, tumors, perioperative data and complications. These data were compared by Student and Khi2 tests. RESULTS: 87 NPS were performed during Period 1 and 137 NPS were performed during period 2. The ASA score of patients undergoing NPESH was higher than NPS (P<0.0001). The tumor complexity and median tumor size were similar in the two groups (P=0.852 and P=0.48). The complication rate for NPS and NPESH was 55.2% and 33.6% (P=0.002). There were less severe complications in the NEPSH group (P=0.012). The median length of stay was 8 and 4 days for the NPS and NPESH groups (P<0.0001). Positive surgical margins were 2 (2.3%) and 6 (4.6%) for the NPS and NPESH group (P=0.713). DISCUSSION: NPESH is an efficient technique compared to NPS. It seems to be an interesting alternative to limit renal ischemia, complication rate and length of stay for the management of localized kidney tumors.

Double J stenting evaluation after ureteroscopy for urolithiasis.

OBJECTIVES: During ureteroscopy for urolithiasis, postoperative ureteral drainage with double J stent is frequently used. It may reduce acute postoperative pain and late ureteral stenosis. Double J stent can have negative impact on life quality. After uncomplicated intervention, double J stent is not mandatory. Objective of our study was to evaluate pain and complications after ureteroscopy with or without stent. METHODS: We retrospectively analyzed ureteroscopy performed between May 2014 and January 2017. Interventions were compared regarding ureteral drainage with double J stent or not. Our primary outcome was early postoperative pain evaluated with an oral pain scale form 1 to 10 on day one after intervention. Clinical characteristics, per- and postoperative data were collected. We also looked for risks factors of complications. RESULTS: Three hundred and sixty-six interventions were included, 259 (70.8%) with and 107 (29.2%) without double J stent. Stone burden was higher in stented group (18.3 vs 9.4mm, P<0.0001). Patients without postoperative stents had more ureteral preparation with double J stent (78.5% vs 62.5%, P=0.0032) and had more ambulatory interventions (75.7% vs 52.5%, P<0.0001). Postoperative pain was not different (22% vs 17.75%, P=0.398). Complication rate was similar (29% vs 20.5%, P=0.1181), so was rehospitalization rate (0.8% vs 0.9%, P=1). In multivariate analysis, complications factors were unprepared ureter, experienced surgeons and access sheath. CONCLUSION: Not stenting after ureteroscopy do not increase pain or complications. Stenting should not be used after uncomplicated interventions for centimetric stones. LEVEL OF EVIDENCE: 4.

Long-term oncological outcomes of cystic renal cell carcinoma according to the Bosniak classification.

OBJECTIVES: To evaluate the prognostic role of the Bosniak classification on the long-term oncological outcomes of cystic renal cell carcinomas. MATERIAL AND METHOD: In a national multicentric retrospective study, we included patients treated surgically for localized cystic RCC from 2000 to 2010. Patients with a follow-up of less than 4 years, benign tumors, and ablative treatments were excluded. The primary outcome was disease-free survival. RESULTS: 152 patients met the inclusion criteria: Bosniak II (6%), III (53%), IV (41%), with a median follow-up of 61 (12-179) months. Characteristics of the population and the tumors were [median, (min-max)] age 57 (25-84) years old, tumor size 43 mm (20-280), RENAL score 7 (4-12), PADUA score 8 (5-14). Treatments were 55% partial nephrectomy, 45% radical nephrectomy, 74% open surgery, and 26% laparoscopy. In pathological report, cystic RCC were mainly of low grade (1-2, 77%) and low stage (pT1, 81%). The two main histological subtypes were conventional (56%) and papillary (23%) RCC. Staging at presentation and histological characteristics were similar between Bosniak III and IV, except for high grade which was more common in Bosniak IV (12 vs 36%, p < 0.01). The Bosniak classification was not predictive of the recurrence, as 5- and 10-year disease-free survival were similar in Bosniak III and IV (92% vs 92% and 84% vs 83%, p = 0.60). CONCLUSION: The Bosniak classification is predictive of the risk of malignancy but not of the oncological prognosis. Regardless of the initial Bosniak categories, almost all cystic RCCs were of low stage/grade and had low long-term recurrence rate.

Who is dying after nephrectomy for cancer? Study of risk factors and causes of death after analyzing morbidity and mortality reviews (UroCCR-33 study).

BACKGROUND AND METHODS: Nephrectomy is the treatment for renal cell cancer from T1-4 tumors but remains at risk. To determine the thirty-day mortality rate after nephrectomy for cancer and to identify causes and risk factors of death in order to find clinical applications. From 2014 to 2017, we performed a retrospective multicentric analysis of prospectively collected data study involving the French network for research on kidney cancer (UroCCR). All patients who died after nephrectomy for cancer during the first thirty days were identified. Patients' characteristics, causes of death and morbidity and mortality reviews reports were analyzed for each death. RESULTS AND LIMITATIONS: In total, 2578 patients underwent nephrectomy and 35 deaths occurred. The thirty-day mortality rate was 1.4%. In univariate analysis, symptoms at diagnosis (P=0.006, OR=2.56 IC (1.3-5.03)), c stage superior to cT1 (P<0.0001, OR=6.13 IC (2.8-13.2)), cT stage superior to cT2 (P<0.0001, OR=8.8 IC (4.39-17.8)), nodal invasion (P<0.0001, OR=4.6 IC (1.9-10.7)), distant metastasis (P=0.001, OR=4.01 IC (1.7-8.9)), open surgery (P<0.0001, OR=0.272 IC (0.13-0.54)) and radical nephrectomy (P=0.007, OR=2.737 IC (1.3-5.7)) were risk factors of thirty-day mortality. In a multivariable model, only cT stage superior to T2 (P=0.015, OR=3.55 IC (1.27-10.01)) was a risk factor of thirty-day mortality. The main cause of postoperative death was pulmonary (n=15; 43%). The second cause was postoperative digestive sepsis for 7 patients (20%). Only 2 morbidity and mortality reviews had been done for the 35 deaths. Limitations are related to the thirty-day mortality criteria and descriptive study design. CONCLUSIONS: Symptomatic patients, stage cTNM and type and techniques of surgery are determinants of thirty-day mortality after nephrectomy for cancer. The first cause of postoperative death is pulmonary. Morbidity and mortality reviews should be considered to better understand causes of death and to reduce early mortality after nephrectomy for cancer. LEVEL OF EVIDENCE: 4.

RETRACTED: Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : prise en charge du cancer du reinFrench ccAFU guidelines ­ Update 2018­2020: Management of kidney cancer / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : prise en charge du cancer du rein.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: DOI:10.1016/j.purol.2019.01.004. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the DOI:10.1016/j.purol.2019.01.004. That newer version of the text should be used when citing the article.

A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry.

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.

[Mini-sling versus transobturator sling: Efficiency and morbidity]. / Mini-bandelette sous-urétrale versus bandelette transobturatrice : efficacité et morbidité.

OBJECTIVE: To compare the effectiveness of an ALTIS® mini-sling and a conventionnal suburethral sling TVT-ABBREVO® for treatment of female stress urinary incontinence. METHODS: A single-center retrospective study included all female patients fitted with a conventional transobturator tape (TVT-ABBREVO®) or mini-sling (ALTIS®), during 2015, in Angers university hospital. The success rate was defined by no urine leakage during a cough test on clinical examination, improved quality of life defined by a PGI-I (Patient Global Impression of Improvement) score of 1 to 3, and no stress urinary incontinence on USP (Urinary Symptom Profile) questionnaire. Morbidity associated with slings and perioperative data were also recorded. RESULTS: Ninety-two patients were included (39 in the ALTIS group and 53 in the ABBREVO group). The average follow-up was 13.55 months. The success rate was not significantly different in ALTIS group for the negative cough test (89.7% vs 94.3% in ABBREVO group, P=0.45), for the absence of urinary leakage reported on the USP questionnaire (87.2% vs 90.6% in ABBREVO group, P=0.61), or for the improvement of the quality of life with a PGI-I score between 1 and 3 (82.1% vs 86.8% in ABBREVO group, P=0.53). On the other hand, more patients were fully satisfied, with a PGI-I quality of life score of 1, in ABBREVO group than in ALTIS group (67.9% compared with 46.2%, P=0.03). Immediate postoperative pain was significantly less intense in ALTIS group than in ABBREVO group (average VAS score of 0.5 comparated with 1.3, P=0.01), but this difference had disappeared one week after surgery. The rates of other complications were similar in both groups. CONCLUSION: The functional results of the ALTIS and TVT-ABBREVO® slings appear similar in the treatment of female stress urinary incontinence.

[Management of metastatic renal cell carcinomass]. / Prise en charge des métastases du cancer du rein.

The management of metastatic renal cell carcinoma had changed over the last ten years with the apparition of new treatments and advances in surgery and ablative techniques. The therapies for metastatic patients have also been personalized and different prognostic groups have been established to adapt the treatment to the severity of the disease. Surgical excision, radiotherapy or ablative therapy could be proposed for patients with isolated metastasis and good condition to delay the systemic therapy initiation. Until 2006, in case of metastatic renal cell carcinoma, immunotherapy (IL-2 and TNF-alpha) was proposed. Targeted therapies acting on angiogenesis mechanisms have also been developed. Recently, immunotherapy has revolutionized the therapeutic management and has improved the overall survival of patients with metastatic renal carcinoma. For each patient, a multidisciplinary management is organized with a personal therapeutic project. This global management needs coordination with the medical team and also need a good communication with the patient, his entourage and his doctor.

[Immunotherapy in renal cell carcinoma: A booming clinical research]. / L'immunothérapie dans le cancer du rein : un développement clinique en plein essor.

CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated. OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area. DOCUMENTARY SOURCE: A systematic review of the literature was performed in PubMed/Medline database and Meeting Library Asco by searching for articles in French or English published on immunotherapy in renal cell carcinoma. The research was limited to abstracts and articles published from 2014 to 2017. SELECTION OF TRIALS: We identified 349 publications and abstracts and selected 17 references from prospective studies. RESULTS: Recent data on checkpoint inhibitors, as well as their combination with tyrosine kinase inhibitors or with anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1 in renal cell carcinoma and the latest advances in vaccine therapy have been reported. CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to lead to a paradigm shift in the clinical management of patients. The combination of nivolumab and ipilimumab in the first line will revolutionize the therapeutic management of patients with metastatic renal cell carcinoma.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.