Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France.

BACKGROUND: Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. METHODS: In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. FINDINGS: Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). INTERPRETATION: In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. FUNDING: Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

Pancreas Preservation: Hypothermic Oxygenated Perfusion to Improve Graft Reperfusion.

BACKGROUND: The clinical standard for pancreas preservation for transplantation is static cold storage (SCS). Oxygenation during preservation has been shown to be advantageous in clinical studies. This study evaluates the efficiency of different oxygenation modalities during hypothermic pancreas preservation. METHODS: Thirty-two porcine pancreases were procured in a controlled donation after circulatory death model and were divided to be preserved in 8 groups: (1) SCS, (2) hypothermic machine perfusion (HMP), (3) hypothermic oxygenated machine perfusion (HOPE) with 21% oxygen, (4) HOPE and 100%, (5) SCS and oxygen carrier, M101, (6) HMP and M101, (7) HOPE 21% and M101, and (8) HOPE 100% and M101. All the groups underwent 24 h of hypothermic preservation, followed by 2 h of normothermic reperfusion. Oxygen partial pressures were assessed using parenchymal probes. Perfusion parameters, perfusate samples, and tissue biopsies were analyzed. RESULTS: This study showed that HMP was linked to higher tissue oxygen partial pressures, lower succinate levels, and better reperfusion parameters. Furthermore, the addition of M101 to either SCS or HMP was associated with lower succinate and creatinine phosphokinase accumulation, suggesting a protective effect against ischemia. CONCLUSIONS: Our research has demonstrated the efficacy of machine perfusion in hypothermic conditions in providing oxygen to the pancreas during preservation and conditioning the pancreatic microvasculature for reperfusion during transplantation. Furthermore, the addition of M101 suggests a protective effect on the graft from ischemia.

Quantification of Urinary Exosomal Prostate-Specific Antigen for the Diagnosis of Prostate Cancer Using Clinical Laboratory-Based Techniques: Protocol for a Case-Control Study.

BACKGROUND: Prostate cancer is the most common cancer in men and represents a major public health problem. The current method for the diagnosis or screening of prostate cancer is invasive and costly. There have been renewed and innovative studies searching for urinary biomarkers to aid in the diagnosis of prostate cancer, especially with technologies based on urinary exosomes. However, technologies based on urine exosomes usually need expensive machines such as an ultracentrifuge and they are difficult to standardize, which hinder their application in clinical laboratories. We have optimized and standardized the isolation of urinary exosomes with the precipitation method. We have found that urinary exosomal prostate-specific antigen (PSA) can be quantified by automatic Elecsys total PSA technique. OBJECTIVE: In this study, our objective is to utilize urinary exosomes from prostate cancer for the development of a test to aid in its diagnosis. METHODS: Exosomes from the prostate cancer cell line LNCaP was used to set up the technique. To analyze urine samples from patients, the methods include the collection of first-void urine using the Colli-Pee device, the isolation of urine exosomes using the optimized precipitation method, and the quantification of exosomal PSA by Elecsys total PSA. RESULTS: This will be a 2-year study. We will start including patients and controls in the last quarter of 2024. We expect the results to be published in the second quarter of 2027. CONCLUSIONS: This is the first study to quantify urinary exosomal PSA using the Elecsys total PSA technique for the diagnosis of prostate cancer. This study emphasizes techniques that are suitable for implementation in clinical laboratories, which will facilitate the application of urinary exosomes to simplify and improve the diagnosis and screening of prostate cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/63551.

Proximal Bilateral Arm Transplantation with Left Shoulder Reconstruction: Outcomes at 24 Months.

Background: Arm transplantation has been proposed as a valid therapeutic option for arm amputees. A bilateral arm transplantation including reconstruction of the left shoulder was performed on January 13, 2021 in Lyon (France). Methods: The recipient was a 48-year-old man with bilateral amputation at proximal arm level on both sides following an electric shock in 1998. He had received a liver transplant in 2002. The donor was a 35-year-old man. On the right side, the donor humerus was fixed on the remaining 9-cm-long proximal stump, and was reinforced with the donor fibula in an intramedullary fashion. On the left side, the whole donor humerus (including the humeral head) was transplanted with reconstruction of the gleno-humeral joint, including a suspension ligamentoplasty. The immunosuppressive protocol was based on antithymocyte globulins as induction therapy, and tacrolimus, steroids and mycophenolate mofetil as maintenance therapy. Results: Good bone healing and a well-positioned ligamentoplasty on the left side were achieved. At 2 years, the recipient was able to flex both elbows, and wrist extension, finger flexion, and extension were appreciated on both sides. Intrinsic muscle activity was detectable by electromyography during the eighth posttransplant month, and sensitivity was recovered. The patient is satisfied with his autonomy in some daily activities, but his greatest satisfaction is the recovery of his body image. Conclusions: These results confirm that it is possible to propose this transplantation to proximal-level arm amputees. The patients' information about risks and limits as well as their compliance and determination remain important prerequisites.

The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis.

Background: About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis. Methods: We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers. Results: Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers. Conclusion: Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Renal and major clinical outcomes and their determinants after nephrectomy in patients with pre-existing chronic kidney disease: A retrospective cohort study.

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.

Young urologists and kidney transplantation training: A survey designed by the French Transplantation Committee of the French Association of Urology (CTAFU) and the French Association of Urologists in training (AFUF).

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.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

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.

Stereotactic body radiotherapy for inoperable patients with renal carcinoma.

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.

Pancreatic Allograft Thrombosis: Implementation of the CPAT-Grading System in a Retrospective Series of Simultaneous Pancreas-Kidney Transplantation.

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.

Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial.

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.

A multicenter comparative matched-pair analysis of percutaneous tumor ablation and robotic-assisted partial nephrectomy of T1b renal cell carcinoma (AblatT1b study-UroCCR 80).

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).

Management and Outcome After Early Renal Transplant Vein Thrombosis: A French Multicentre Observational Study of Real-Life Practice Over 24 Years.

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.

Prostatic arterial embolization versus holmium laser enucleation of the prostate: 1-year outcomes.

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.

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Cancer: 24-Month Results of the RSR1 Phase 1 Dose Escalation Study.

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.

[Organ conservation and transportation modalities]. / Modalités de conservation et de transport des organes.

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.

En Bloc Kidney Transplantation: A Retrospective Study of an 18-year Experience in a Single Institution.

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.

A New Animal Model of Laryngeal Transplantation.

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.

Inverted direct allorecognition triggers early donor-specific antibody responses after transplantation.

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.

Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process.

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.