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1.
PLoS One ; 19(5): e0300367, 2024.
Article En | MEDLINE | ID: mdl-38696458

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.


Glomerular Filtration Rate , Nephrectomy , Renal Insufficiency, Chronic , Humans , Nephrectomy/adverse effects , Nephrectomy/methods , Male , Female , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/surgery , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Middle Aged , Aged , Risk Factors , Kidney Neoplasms/surgery , Kidney Neoplasms/complications , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Treatment Outcome , Kidney/surgery , Kidney/physiopathology , Solitary Kidney/surgery , Solitary Kidney/complications
2.
Fr J Urol ; 34(5): 102611, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38460937

OBJECTIVE: In France, kidney transplantations (KT) are mainly performed by urologist. Young urologists and residents are involved in this activity mostly performed in emergency. How do they feel about KT training? Is KT an attractive part of the urologist activity? METHODS: This survey has been designed in the form of a questionnaire by the French Committee of Kidney Transplantation (CTAFU) and the French Association of Urologists in training (AFUF). It has been sent by e-mail to all the AFUF members. Interest in KT and performance of the training were evaluated. RESULTS: In total, 126 members filed the form. Among the residents, 51.5% feel secure to perform KT at the end of their residency. KT is considered as an interesting surgery for 92.1% of the participants: 76.5% are willing to get involved in KT during their residency/fellowship. Among the participants, 44% are willing to continue a long-term involvement. Among the residents, 65.9% consider their practical training insufficient: 56.8% have been supervised for a KT performance during their residency and 86% declare a lack of practical training and had a patient-based learning. Among the residents, 92.1% declare an insufficient theorical training. Among the residents, 33.3% say the schedules of transplantation limit their interest in KT. Among the participants, 34.4% receive a transplant bonus in addition to the usual on-call salary. CONCLUSION: Young urologists wish to continue their involvement in KT activity, but improved theoretical and practical training are essential. In addition, the conditions under which this activity is performed and remunerated are a matter of concern.

3.
Eur Urol Oncol ; 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38493072

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

4.
Fr J Urol ; 34(2): 102575, 2024 Mar.
Article En | MEDLINE | ID: mdl-38364353

INTRODUCTION: The objective of this study was to analyze the dose-dependent safety profiles of stereotactic body radiation therapy (SBRT) in patients with inoperable small renal cell carcinoma (RCC). MATERIAL: This is a retrospective study from a single institution including patients with RCC treated between 2011 and 2020 with SBRT on the primary tumor or on a local recurrence after surgery. All patients had been declared inoperable or refused surgery. The patients were divided into two dose level groups: group 1 (BED10<60Gy) and group 2 (BED10≥60Gy). Acute and late toxicities, renal function and local control (LC) were compared between the two groups. RESULTS: A total of 24 patients were analyzed with an average follow-up of 25.1 months. Nine patients (37%) and three patients (14%) reported grade 1-2 acute and late toxicities, respectively. No grade≥3 acute and late toxicities were observed. There was no significant difference in acute and late toxicities between the two groups (P=0.21 and P=0.27, respectively). There was no significant difference in estimated glomerular filtration rate in the 15 patients, eligible for renal toxicity analysis between the pre-radiation and the 12-month follow-up (P=0.1) and the last follow-up (P=0.06). LC at the last follow-up was noted in 19 out of 23 patients (83%) and was based on imaging acquisition. LC was 77.8% for group 1 and 85.7% for group 2 (P=1.95). CONCLUSION: Dose escalation was not associated with an increase in acute and late grade≥2 toxicities. There appears to be a trend towards increased LC at higher doses.


Carcinoma, Renal Cell , Kidney Neoplasms , Radiosurgery , Humans , Radiosurgery/methods , Radiosurgery/adverse effects , Carcinoma, Renal Cell/radiotherapy , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Male , Retrospective Studies , Female , Aged , Middle Aged , Aged, 80 and over , Radiotherapy Dosage , Dose-Response Relationship, Radiation
5.
Transpl Int ; 36: 11520, 2023.
Article En | MEDLINE | ID: mdl-37720417

Pancreatic graft thrombosis (PAT) is a major surgical complication, potentially leading to graft loss. The recently proposed Cambridge Pancreas Allograft Thrombosis (CPAT) grading system provides diagnostic, prognostic and therapeutic recommendations. The aim of the present study was to retrospectively assess computed tomography angiography (CTA) examinations performed routinely in simultaneous pancreas-kidney (SPK) recipients to implement the CPAT grading system and to study its association with the recipients' outcomes. We retrospectively studied 319 SPK transplant recipients, who underwent a routine CTA within the first 7 postoperative days. Analysis of the CTA scans revealed PAT in 215 patients (106 grade 1, 85 grade 2, 24 grade 3), while 104 showed no signs. Demographic data of the patients with and without PAT (thrombosis and non-thrombosis group) were not significantly different, except for the higher number of male donors in the thrombosis group. Pancreatic graft survival was significantly shorter in the thrombosis group. Graft loss due to PAT was significantly associated with grade 2 and 3 thrombosis, while it did not differ for recipients with grade 0 or grade 1 thrombosis. In conclusion, the CPAT grading system was successfully implemented in a large series of SPK transplant recipients and proved applicable in clinical practice.


Kidney Transplantation , Pancreas Transplantation , Humans , Male , Retrospective Studies , Kidney Transplantation/adverse effects , Pancreas , Pancreas Transplantation/adverse effects , Allografts
6.
Trials ; 24(1): 302, 2023 May 01.
Article En | MEDLINE | ID: mdl-37127632

BACKGROUND: Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts. METHODS: OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation. DISCUSSION: The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04181710 . registered on November 29, 2019.


Kidney Transplantation , Humans , Organ Preservation , Oxygen , Prospective Studies , Kidney , Graft Survival , Perfusion/methods , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
7.
Transpl Int ; 36: 10556, 2023.
Article En | MEDLINE | ID: mdl-37035106

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.


Kidney Diseases , Kidney Transplantation , Venous Thrombosis , Adult , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Venous Thrombosis/etiology , Venous Thrombosis/surgery , Kidney , Kidney Diseases/etiology , Thrombectomy/adverse effects , Thrombectomy/methods , Retrospective Studies
8.
Eur Radiol ; 33(9): 6513-6521, 2023 Sep.
Article En | MEDLINE | ID: mdl-37004570

OBJECTIVE: Renal cell carcinomas represent the sixth- and tenth-most frequently diagnosed cancer in men and women. Recently, percutaneous-guided thermal ablations have proved to be as effective as partial nephrectomy and safer for treating small renal masses (i.e., < 3 cm). This study compared the perioperative and recurrence outcomes of percutaneous thermal ablation (TA) and robotic-assisted partial nephrectomy (RAPN) for the treatment of T1b renal cell carcinomas (4.1-7 cm). METHODS: Retrospective data from 11 centers on the national database, between 2010 and 2020, included 81 patients treated with thermal ablation (TA) and 308 patients treated with RAPN for T1b renal cell carcinoma, collected retrospectively and matched for tumor size, histology results, and the RENAL score. TA included cryoablation and microwave ablation. Endpoints compared the rate between the two groups: local recurrence, metastases, complications, renal function decrease, and length of hospitalization. RESULTS: After matching, 75 patients were included in each group; mean age was 76.6 (± 9) in the TA group and 61.1 (± 12) in the RAPN group, including 69.3% and 76% men respectively. The local recurrence (LR) rate was significantly higher in the TA group than in the PN group (14.6% vs 4%; p = 0.02). The LR rate was 20% (1/5) after microwave ablation, 11.1% (1/9) after radiofrequency ablation, and 14.7% (9/61) after cryoablation. The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs 0%; p < 0.001). Metastases, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: The local recurrence rate was significantly higher after thermal ablation; however, thermal ablation resulted in significantly lower rates of complications. Thermal ablation and robotic-assisted partial nephrectomy are effective treatments for T1b renal cancer; however, the local recurrence rate was higher after thermal ablation. KEY POINTS: • The local recurrence rate was significantly higher in the thermal ablation group than in the partial nephrectomy group. • The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs. 0%; p < 0.001).


Carcinoma, Renal Cell , Kidney Neoplasms , Robotic Surgical Procedures , Male , Humans , Female , Aged , Carcinoma, Renal Cell/pathology , Retrospective Studies , Robotic Surgical Procedures/methods , Matched-Pair Analysis , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Nephrectomy/methods , Treatment Outcome
9.
World J Urol ; 41(1): 151-157, 2023 Jan.
Article En | MEDLINE | ID: mdl-36451037

PURPOSE: Holmium Laser Enucleation of the Prostate (HoLEP) and Prostatic Artery Embolization (PAE) are novel techniques for the treatment of benign prostatic hyperplasia lower urinary tract symptoms (BPH-LUTS). The objective of this study was to describe and compare the functional results and complications of these two techniques at one year follow-up. MATERIALS AND METHODS: We performed a retrospective, monocentric study of all patients consecutively treated in our center with HoLEP or PAE for symptomatic or complicated BPH between January 2016 and December 2019. Data regarding patient and perioperative characteristics, follow-up biological results, functional questionnaires and uroflowmetry were collected from medical records. RESULTS: A total of 490 and 57 patients were treated with HoLEP and PAE, respectively. The demographic and clinical characteristics of the two groups were similar. The operative time was significantly higher for PAE (p < 0.001) and hospitalization time longer after HoLEP (p = 0.0006). The urinary catheterization time was longer after PAE (p < 0.001). The prostatic volume treated was higher with HoLEP than with PAE (56% versus 26%, p < 0.001). The mean difference in IPSS from baseline to 12 months was significantly higher after HoLEP than after PAE: - 17.58 versus - 8 (p < 0.001). The mean difference in QoL-IPSS from baseline to 12 months was significantly higher after HoLEP: - 4.09 versus - 2.27 (p < 0.001). The rate of postoperative adverse events in the first three months was similar between the two groups:35% after HoLEP and 33% after PAE (p = 0.88). CONCLUSIONS: HoLEP and PAE both significantly improved BPH-LUTS, with HoLEP having an advantage over PAE.


Embolization, Therapeutic , Laser Therapy , Lasers, Solid-State , Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Male , Humans , Prostate/surgery , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/complications , Lasers, Solid-State/therapeutic use , Retrospective Studies , Quality of Life , Treatment Outcome , Laser Therapy/methods , Lower Urinary Tract Symptoms/therapy , Lower Urinary Tract Symptoms/complications , Holmium
10.
Pract Radiat Oncol ; 13(1): e73-e79, 2023.
Article En | MEDLINE | ID: mdl-35842186

PURPOSE: Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT. METHODS AND MATERIALS: This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0. RESULTS: From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease. CONCLUSIONS: After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies.


Carcinoma, Renal Cell , Kidney Neoplasms , Radiosurgery , Humans , Carcinoma, Renal Cell/radiotherapy , Radiosurgery/adverse effects , Radiosurgery/methods , Kidney Neoplasms/radiotherapy , Maximum Tolerated Dose
11.
Rev Prat ; 73(9): 964-968, 2023 Nov.
Article Fr | MEDLINE | ID: mdl-38294444

ORGAN CONSERVATION AND TRANSPORTATION MODALITIES. Organ preservation in transplantation is an essential step in the graft journey between the donor and the recipient. The modalities of preservation have become a major element in this process given the evolution of donors in terms of age and associated comorbidities. This situation has led to the evolution of preservation in terms of the composition of solutions and perfusion technologies for all organs. Several concepts have thus emerged with extracellular type composition and the contribution of new molecules such as high molecular weight polyethylene glycols. The evolution also concerns new techniques such as normothermic abdominal circulation and perfusion machines with the use of hypothermia or normothermia and the oxygenation of the medium. Finally, new molecules are available to the teams and other concepts such as perfusion, evaluation and rehabilitation units.


MODALITÉS DE CONSERVATION ET DE TRANSPORT DES ORGANES. La conservation des organes est une étape essentielle dans le parcours du greffon entre le donneur et le receveur. Les modalités de conservation sont devenues un élément majeur dans ce processus compte tenu de l'évolution de l'âge des donneurs et des comorbidités associées. Cette situation a conduit à faire évoluer la conservation en matière de composition des solutions et de technologie de perfusion, et cela pour tous les organes. Plusieurs concepts ont ainsi émergé, avec la composition de type extracellulaire et l'apport de nouvelles molécules comme les polyéthylènes glycols de haut poids moléculaire. Les progrès concernent aussi de nouvelles techniques, comme la circulation régionale normothermique et les machines de perfusion avec l'utilisation de l'hypothermie ou de la normothermie et l'oxygénation du milieu. Enfin, de nouvelles molécules sont à disposition des équipes, et d'autres concepts se développent, comme les unités de perfusion, d'évaluation et de réhabilitation.


Medicine , Humans , Polyethylene Glycols , Tissue Donors
12.
Eur Urol Open Sci ; 46: 137-144, 2022 Dec.
Article En | MEDLINE | ID: mdl-36506250

Background: Renal transplantation is facing a shortage of grafts. En bloc kidney transplantation (EBKT) from pediatric donors could increase the number of available grafts. Objective: To describe the surgical technique as well as the long-term functional and morphological results of EBKT. Design setting and participants: We performed a retrospective study of all the EBKT procedures performed in Lyon between 2002 and 2020. Electronic medical records were checked with an analysis of demographics, and peri- and postoperative results. Outcome measurements and statistical analysis: A descriptive analysis of donor and recipient characteristics, perioperative data, complications, and renal function was performed. Results and limitations: Between 2002 and 2020, 21 EBKT procedures were performed. Donors had a mean weight of 8.6 kg and a mean age of 12 mo, with a mean cold ischemia time of 11 h and 30 min. Receivers had a mean age of 30 yr and a body mass index of 20. The mean follow-up time was 62 mo, with patient survival of 100% and graft survival of 95%. There were 13 reinterventions comprising one early unilateral transplantectomy for thrombosis. Renal function was excellent, and the morphological findings described an important growth in size in the first 2 yr before attaining the adult size. This study's limitations include its retrospective nature and a small number of participants. Conclusions: The present study reports excellent results with EBKT and supports the pursuit and spread of this technique. Patient summary: In this report, we describe the technique and results of en bloc kidney transplantation. We found that results are excellent for renal function and patient survival. We conclude that en bloc kidney transplantation should be considered to increase the number of grafts.

13.
J Clin Med ; 11(21)2022 Oct 30.
Article En | MEDLINE | ID: mdl-36362655

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

14.
Sci Transl Med ; 14(663): eabg1046, 2022 Sep 21.
Article En | MEDLINE | ID: mdl-36130013

The generation of antibodies against donor-specific major histocompatibility complex (MHC) antigens, a type of donor-specific antibodies (DSAs), after transplantation requires that recipient's allospecific B cells receive help from T cells. The current dogma holds that this help is exclusively provided by the recipient's CD4+ T cells that recognize complexes of recipient's MHC II molecules and peptides derived from donor-specific MHC alloantigens, a process called indirect allorecognition. Here, we demonstrated that, after allogeneic heart transplantation, CD3ε knockout recipient mice lacking T cells generate a rapid, transient wave of switched alloantibodies, predominantly directed against MHC I molecules. This is due to the presence of donor CD4+ T cells within the graft that recognize intact recipient's MHC II molecules expressed by B cell receptor-activated allospecific B cells. Indirect evidence suggests that this inverted direct pathway is also operant in patients after transplantation. Resident memory donor CD4+ T cells were observed in perfusion liquids of human renal and lung grafts and acquired B cell helper functions upon in vitro stimulation. Furthermore, T follicular helper cells, specialized in helping B cells, were abundant in mucosa-associated lymphoid tissue of lung and intestinal grafts. In the latter, more graft-derived passenger T cells correlated with the detection of donor T cells in recipient's circulation; this, in turn, was associated with an early transient anti-MHC I DSA response and worse transplantation outcomes. We conclude that this inverted direct allorecognition is a possible explanation for the early transient anti-MHC DSA responses frequently observed after lung or intestinal transplantations.


Antibody Formation , Isoantibodies , Animals , Graft Rejection , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Humans , Isoantigens , Mice , Mice, Inbred BALB C , Peptides , Receptors, Antigen, B-Cell
15.
Int J Mol Sci ; 23(9)2022 Apr 30.
Article En | MEDLINE | ID: mdl-35563381

Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft's short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice.


Hypothermia , Tissue and Organ Procurement , Humans , Organ Preservation , Perfusion , Tissue Donors
16.
Eur Urol Focus ; 8(5): 1226-1237, 2022 09.
Article En | MEDLINE | ID: mdl-34172421

BACKGROUND: Delay in treatment is a prognostic factor in muscle-invasive bladder cancer. OBJECTIVE: To evaluate clinical outcomes associated with delays in diagnosis and treatment for patients with non-muscle invasive bladder cancer (NMIBC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study we analyzed data for patients treated at our center between November 2008 and December 2016 for intermediate risk (IR) or high risk (HR) NMIBC with an additional intravesical treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time delays from diagnosis to first transurethral resection (TT-TUR), from resection to restaging resection (TT-reTUR), and from the last resection to first instillation (TT-INST) of bacillus Calmette-Guérin (BCG) or mitomycin C (MMC) were documented. To identify the interval of time from which recurrence rates significantly increased, we used nonparametric series regression. Recurrence-free survival (RFS) and progression-free survival for patients in each time delay category were compared using the Kaplan-Meier method. Factors associated with tumor recurrence were analyzed in a multivariable model. RESULTS AND LIMITATIONS: A total of 434 patients were included, of whom 168 (38.7%) had IR and 266 (61.3%) had HR NMIBC. Among the patients, 34.6% had reTUR, 63.6% received BCG, and 36.4% received MMC. The median TT-TUR, TT-reTUR, and TT-INST was 4.0 wk, 6.5 wk, and 7.0 wk, respectively. At 40 mo the rate of recurrence was 28.4% and the rate of progression was 7.3%. Nonparametric analysis revealed that each week in delay increased the risk of recurrence, starting from week 6 for TT-TUR for IR and HR cases, and starting from week 7 for TT-INST for IR cases. RFS was significantly lower with TT-TUR > 6 wk among patients in the IR (p < 0.001) and HR (p = 0.04) groups, and with TT-INST >7 wk for patients in the IR group (p = 0.001). TT-reTUR >7 wk had a significant negative impact on progression (p < 0.017). Multivariable analysis revealed that for IR and HR cases, multifocality (p = 0.02 and p = 0.007) and TT-TUR >6 wk (p = 0.001 and p = 0.03) were independent predictors of recurrence, while TT-INST >7 wk predicted recurrence (p = 0.04) for IR NMIBC. CONCLUSIONS: Our results suggest that delays of >6 wk to first TUR in IR and HR NMIBC, and >7 wk to first instillation in IR cases are associated with increases in the risk of recurrence. TT-reTUR of >7 wk is also associated with higher risk of progression. PATIENT SUMMARY: We evaluated the impact of treatment delays on outcomes for patients with intermediate- and high-risk bladder cancer not invading the bladder wall muscle. We found that delays from diagnosis to first bladder resection, from first resection to repeat resection, and from last resection to bladder instillation treatment increase the rates of cancer recurrence and progression. The medical team should avoid delays in treatment, even for low-grade bladder cancer.


Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Retrospective Studies , Prognosis , BCG Vaccine/therapeutic use , Time-to-Treatment , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Neoplasm Invasiveness , Mitomycin/therapeutic use
17.
BJU Int ; 129(2): 225-233, 2022 02.
Article En | MEDLINE | ID: mdl-34114727

OBJECTIVES: To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS: The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Données Informatisées et VAlidées en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS: Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P < 0.001) and especially with stenosis and ureteric fistulae at 1 year. There is no association with LD, uncontrolled and controlled DCD. The placement of an endo-ureteric stent was beneficial in preventing urinary complications in all donors and particularly in ECD donors. CONCLUSION: The donor's ECD status is associated with a higher likelihood of stenosis and ureteric fistulae at 1 year. Recipients of grafts from ECD donors should probably be considered for closer urological monitoring and systematic preventive measures.


Kidney Transplantation , Tissue and Organ Procurement , Adult , Cohort Studies , Constriction, Pathologic/etiology , Graft Survival , Humans , Kidney , Kidney Transplantation/adverse effects , Living Donors , Prospective Studies , Retrospective Studies , Tissue Donors , Treatment Outcome
18.
Nephrol Dial Transplant ; 37(5): 982-990, 2022 04 25.
Article En | MEDLINE | ID: mdl-34748014

BACKGROUND: This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). METHODS: Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. RESULTS: The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. CONCLUSIONS: In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.


Kidney Transplantation , Graft Survival , Humans , Kidney , Retrospective Studies , Tissue Donors , Treatment Outcome
19.
Artif Organs ; 46(4): 597-605, 2022 Apr.
Article En | MEDLINE | ID: mdl-34951495

BACKGROUND: M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO2 life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO2 life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO2 life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys. METHODS: An additional analysis was conducted including OXYOP patients and patients from the ASTRE database (n = 6584) to verify that the decrease in DGF rates observed in the HEMO2 life® group may not be due solely to the shorter CIT but also to HEMO2 life® performance. Kaplan-Meier estimate curves of cumulative probability of achieving a creatinine level below 250 µmol/L were generated and compared in both groups. A Cox model was used to test the effect of the explanatory variables (use of HEMO2 life® and CIT). Finally, a bootstrap strategy was used to randomly select smaller samples of patients and test them for statistical comparison in the ASTRE database. RESULTS: Kaplan-Meier estimate curves confirmed the existence of a relation between DGF and CIT and Cox analysis showed a benefit in the HEMO2 life® group regardless of the associated CIT. Boostrap analysis confirmed these results. CONCLUSIONS: The present study suggested that the better recovery of renal function observed among kidneys preserved with HEMO2 life® in the OXYOP study is a therapeutic benefit of this breakthrough innovative medical device.


Cold Ischemia , Kidney Transplantation , Cold Ischemia/adverse effects , Cold Ischemia/methods , Delayed Graft Function , Graft Survival , Hemoglobins , Humans , Kidney/physiology , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Prospective Studies , Risk Factors
20.
Transpl Int ; 34(9): 1656-1666, 2021 Sep.
Article En | MEDLINE | ID: mdl-34448267

Normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) is a promising procurement strategy. However, a detailed analysis of graft utilization rates is lacking. This retrospective study included all cDCD donors proposed to a single center for NRP procurement of at least one abdominal organ from 2015 to 2020. Utilization rates were defined as the proportion of transplanted grafts from proposed donors in which withdrawal of life sustaining therapies (WLST) was initiated. In total, 125 cDCD donors underwent WLST with transplantation of at least one graft from 109 (87%) donors. In a total of 14 (11%) procedures NRP failure led to graft discard. Utilization rates for kidney and liver grafts were 83% and 59%, respectively. In 44% of the discarded livers, the reason was poor graft quality based on functional donor warm ischemia >45 min, macroscopic aspect, high-transaminases release, or pathological biopsy. In this study, abdominal NRP in cDCD lead to transplantation of at least one graft in the majority of cases. While the utilization rate for kidneys was high, nearly half of the liver grafts were discarded. Cannulation training, novel graft viability markers, and ex-vivo liver graft perfusion may allow to increase graft utilization.


Organ Preservation , Tissue and Organ Procurement , France , Graft Survival , Humans , Perfusion , Retrospective Studies , Tissue Donors
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