Trasplante renal abierto frente a trasplante renal asistido por robot: revisión sistemática del grupo de trabajo de trasplante renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU) / Open versus robotic-assisted kidney transplantation: A systematic review by the European Association of Urology (EAU) – Young Academic Urologists (YAU) Kidney Transplant Working Group

Introducción En los últimos 20 años se ha evaluado el uso de la robótica en el campo del trasplante renal como abordaje miniinvasivo a esta población especialmente vulnerable. Al tratarse de un campo relativamente novedoso, pocos estudios han comparado el trasplante renal abierto (TRA) y el trasplante renal asistido por robot (TRAR), la mayoría en cohortes pequeñas. Para ampliar los conocimientos actuales, hemos querido reunir en este documento datos comparativos de TRA frente a TRAR en una revisión sistemática. Métodos Se realizó una revisión sistemática de acuerdo con la declaración de Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Se realizaron búsquedas en las bases de datos Medline, Embase y Cochrane para identificar todos los estudios que informaran sobre los resultados postoperatorios del TRAR frente al TRA. Resultados Un total de 2.136 pacientes de 13 estudios fueron incluidos. La mediana de edad de los receptores fue de 42,6 años (TRA: 43,5 años y TRAR: 40,3 años). La mediana de la tasa de trasplante renal preventivo fue de 27,1% (TRA: 23,3% y TRAR: 33,2%). La mediana del tiempo quirúrgico total y de recalentamiento fueron: 235 y 49 min, respectivamente, en la población TRA; 250 y 60 min en la población TRAR. Las tasas de complicaciones postoperatorias fueron: 26,2% en la población TRA y 17,8% en la población TRAR. Las tasas de retraso en la función del injerto fueron: 4,9% en la población TRA y 2,3 en la población TRAR. Los resultados funcionales a medio plazo y la supervivencia del paciente y del injerto fueron similares entre las poblaciones TRA y TRAR. Conclusión Esta revisión sistemática demostró que el TRAR puede asociarse a una menor incidencia de retraso en la función del injerto y de complicaciones quirúrgicas postoperatorias, así como a unos resultados funcionales a medio plazo y una supervivencia del paciente y del injerto similares, en comparación con el TRA para los pacientes con enfermedad renal terminal (AU)

Introduction In the last 20 years, robotic assisted procedures were evaluated in the field of kidney transplantation to provide a mini-invasive approach for this particularly fragile population. As a relatively new issue, few studies compared open kidney transplantation (OKT) and robotic-assisted kidney transplantation (RAKT), mostly in small cohorts. To improve current knowledge, we wanted here to gather comparative data of OKT vs RAKT in a systematic review. Methods A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline, Embase, and Cochrane databases were searched to identify all studies reporting post-operative outcomes of RAKT versus OKT. Results A total of 2,136 patients in 13 studies were included. Median recipient age was 42.6 years (OKT: 43.5 years and RAKT: 40.3 years). Median preemptive kidney transplantation rate was 27.1% (OKT: 23.3% and RAKT: 33.2%). Median total operative time and rewarming were respectively: 235 and 49 minutes in OKT population; 250 and 60 minutes in RAKT population.Post-operative complications rates were: 26.2% in OKT population and 17.8% in RAKT population. Delayed graft function rates were: 4.9% in OKT population and 2.3 in RAKT population. Mid-term functional outcomes, patient and graft survival were similar in OKT and RAKT population. Conclusion This systematic review showed that RAKT may be associated with a lower incidence of delayed graft function and post-operative surgical complications and similar mid-term functional outcomes, patient and graft survival, compared to OKT for end-stage renal disease patients (AU)

Nefroureterectomía radical asistida por robot para el carcinoma urotelial del tracto urinario superior: resultados peri y postoperatorios / Robot-assisted radical nephroureterectomy for upper tract urothelial carcinoma: Peri and postoperative outcomes

Introducción La nefroureterectomía radical constituye el tratamiento de los tumores uroteliales del tracto urinario superior con alto riesgo de mortalidad específica. La nefroureterectomía radical laparoscópica asistida por robot (NURAR) todavía está siendo investigada para establecer de manera concluyente la seguridad del procedimiento en el tratamiento de los tumores uroteliales del tracto urinario superior. El objetivo principal es evaluar la seguridad intra y postoperatoria de la NURAR y, posteriormente, evaluar los resultados oncológicos a mediano plazo. Métodos Se trata de un estudio retrospectivo monocéntrico basado en una recopilación de NURAR realizadas entre el 1 de enero de 2015 y el 1 de octubre de 2021. Las NURAR se llevaron a cabo con la asistencia del robot Da Vinci Si® y, desde 2017, con el robot Da Vinci Xi®. Siempre que fue posible, la totalidad del procedimiento se llevó a cabo sin reacoplamiento (re-docking). Resultados Entre el 1 de enero de 2015 y el 1 de octubre de 2021, se realizaron 29 NURAR en nuestro centro. En el 80% de los casos se pudo realizar toda la cirugía sin reacoplamiento con el robot Da Vinci Xi®. Un paciente requirió conversión a cirugía abierta por dificultad en la disección. El 50% de los tumores se clasificaron como T3 o T4. La tasa de complicaciones a los 30 días fue del 31%. La duración media de la estancia hospitalaria fue de 5 días. La supervivencia libre de enfermedad en el tiempo medio de supervivencia (27,5 meses) fue del 75,2%. Un paciente tuvo una recidiva en el compartimento de la nefrectomía y ningún paciente tuvo recidiva peritoneal o en los orificios de los trocares. Conclusión La realización de NURAR para el tratamiento de los tumores del tracto urinario superior parece cumplir los criterios de seguridad quirúrgica y oncológica (AU)

Introduction The treatment of urothelial tumours of the upper urinary tract at high risk of specific mortality is based on radical nephroureterectomy. Robotic-assisted laparoscopic radical nephroureterectomy (RARNU) is still under investigation to definitively establish the safety of this procedure in the management of urothelial tumours of the upper urinary tract. The primary objective is to evaluate the intra- and postoperative safety of RARNU and, subsequently, to evaluate the medium-term oncological results. Methods Our study is a retrospective, mono-centric study with a collection of RARNUs conducted between 1st January 2015 and 1st October 2021. The RARNUs were performed with the assistance of the Da Vinci Si® robot, then from 2017 the Da Vinci Xi® robot. Whenever possible, the entire procedure was carried out without re-docking. Results Between 1st January 2015 and 1st October 2021, 29 RARNUs were carried out at our centre. Complete surgery without re-docking was possible in 80% of cases with the Da Vinci Xi® robot. One patient required conversion to open surgery due to difficult dissection. A percentage of 50 of tumours were classified as T3 or T4. The 30-day complication rate was 31%. The median length of hospitalisation was 5 days. The disease-free survival at the mean survival time (27.5 months) was of 75.2%. One patient had a recurrence in the nephrectomy compartment and no patient had a peritoneal or trocar orifice recurrence. Conclusion Performing RARNU for the management of tumours of the upper urinary tract appears to meet the criteria of surgical safety and those of oncological safety (AU)

Trasplante renal en receptor pediátrico: consideraciones y estrategias de evaluación preoperatoria / Renal transplantation in pediatric recipients: Considerations and preoperative assessment strategies

Introducción y objetivo El trasplante renal en la población pediátrica difiere del trasplante en adultos en muchos aspectos. Esta revisión se centrará en los aspectos exclusivos del receptor pediátrico. Material y métodos Se realizó una revisión narrativa de la escasa literatura existente sobre la evaluación preoperatoria del trasplante renal en receptor pediátrico con un enfoque educativo. La búsqueda bibliográfica permitió identificar publicaciones en inglés entre enero de 2000 y octubre de 2022. Los estudios publicados se identificaron mediante búsquedas en las siguientes bases de datos electrónicas: PubMed (Medline), WHO/UNAIDS, Google-Scholar, Semantic-Scholar y Research Gate. En aras de la eficacia y la fiabilidad, se utilizaron ensayos controlados aleatorizados, metaanálisis, revisiones sistemáticas de alta calidad y estudios grandes recientes bien diseñados, si estaban disponibles. Se realizaron búsquedas en internet para obtener información pertinente adicional (definiciones, políticas o directrices). Resultados El manejo de las anomalías urogenitales congénitas y la disfunción del tracto urinario inferior, junto con la evaluación urológica pediátrica preoperatoria óptima para el trasplante renal en niños, se ha abordado según la bibliografía disponible. Adicionalmente, se han mencionado consideraciones particulares relativas al trasplante preventivo y al trasplante de un riñón de tamaño adulto en un lactante o un niño pequeño. Conclusiones Los resultados del trasplante renal en niños han mejorado progresivamente en los últimos 15años. El trasplante de donante vivo emparentado ofrece los mejores resultados, y el trasplante preventivo puede ayudar a evitar la diálisis. Las consideraciones quirúrgicas y médicas, tanto en el tratamiento pretrasplante como en el postrasplante del receptor renal pediátrico, son extremadamente importantes para obtener resultados mejores a corto y a largo plazo (AU)

Introduction and objective Renal transplantation in the pediatric population differs from adults in many aspects. This review will focus on the unique issues of the pediatric recipient. Material and methods A narrative review on the scarce literature regarding preoperative evaluation before kidney transplantation of the paediatric recipient with an educational focus was conducted. The literature search allowed for identification of publications in English from January 2000 to October 2022. Published studies were identified by searching the following electronic databases: PubMed (Medline), WHO/UNAIDS, Google-Scholar, Semantic-Scholar and Research Gate. For efficiency and reliability, recent randomized controlled trials, meta-analyses, high quality systematic reviews and large well-designed studies were used if available. Internet searches were conducted for other relevant information (definitions, policies or guidelines). Results Management of congenital urogenital anomalies and lower urinary tract dysfunction along with optimal pediatric urological preoperative assessment for renal transplantation in children is addressed in the light of the available literature. Furthermore, particular considerations including pre-emptive transplantation, transplantation of an adult-size kidney into an infant or small child is discussed. Conclusions Outcomes of renal transplantation in children have shown progressive improvement over the past 15years. Transplantation with living related donor gives the best results and pre-emptive transplantation provides with benefits of avoiding dialysis. Surgical and medical considerations in both the pre-transplant and post-transplant management of the pediatric kidney recipient are extremely crucial in order to achieve better short and long-term results (AU)

Robot-assisted radical nephroureterectomy for upper tract urothelial carcinoma: Peri and postoperative outcomes.

INTRODUCTION: The treatment of urothelial tumours of the upper urinary tract at high risk of specific mortality is based on radical nephroureterectomy (RNU). Robotic-assisted laparoscopic radical nephroureterectomy (RARNU) is still under investigation to definitively establish the safety of this procedure in the management of urothelial tumours of the upper urinary tract. The primary objective is to evaluate the intra- and postoperative safety of RARNU and, subsequently, to evaluate the medium-term oncological results. METHODS: Our study is a retrospective, mono-centric study with a collection of RARNUs conducted between 1st January 2015 and 1st October 2021. The RARNUs were performed with the assistance of the Da Vinci Si® robot, then from 2017 the Da Vinci Xi® robot. Whenever possible, the entire procedure was carried out without re-docking. RESULTS: Between 1st January 2015 and 1st October 2021, 29 RARNUs were carried out at our centre. Complete surgery without re-docking was possible in 80% of cases with the Da Vinci Xi® robot. One patient required conversion to open surgery due to difficult dissection. 50% of tumours were classified as T3 or T4. The 30-day complication rate was 31%. The median length of hospitalisation was 5 days. The disease-free survival at the mean survival time (27.5 months) was of 75.2%. One patient had a recurrence in the nephrectomy compartment and no patient had a peritoneal or trocar orifice recurrence. CONCLUSION: Performing RARNU for the management of tumours of the upper urinary tract appears to meet the criteria of surgical safety and those of oncological safety.

Open versus robotic-assisted kidney transplantation: A systematic review by the European Association of Urology (EAU) - Young Academic Urologists (YAU) Kidney Transplant Working Group.

INTRODUCTION: In the last 20 years, robotic assisted procedures were evaluated in the field of kidney transplantation to provide a mini-invasive approach for this particularly fragile population. As a relatively new issue, few studies compared open kidney transplantation (OKT) and robotic-assisted kidney transplantation (RAKT), mostly in small cohorts. To improve current knowledge, we wanted here to gather comparative data of OKT vs RAKT in a systematic review. METHODS: A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline, Embase, and Cochrane databases were searched to identify all studies reporting post-operative outcomes of RAKT versus OKT. RESULTS: A total of 2136 patients in 13 studies were included. Median recipient age was 42.6 years (OKT: 43.5 years and RAKT: 40.3 years). Median preemptive kidney transplantation rate was 27.1 % (OKT: 23.3 % and RAKT: 33.2 %). Median total operative time and rewarming were respectively: 235 and 49 min in OKT population; 250 and 60 min in RAKT population. Post-operative complications rates were: 26.2 % in OKT population and 17.8 % in RAKT population. Delayed graft function rates were: 4.9 % in OKT population and 2.3 in RAKT population. Mid-term functional outcomes, patient and graft survival were similar in OKT and RAKT population. CONCLUSION: This systematic review showed that RAKT may be associated with a lower incidence of delayed graft function and post-operative surgical complications and similar mid-term functional outcomes, patient and graft survival, compared to OKT for end-stage renal disease patients.

Renal transplantation in pediatric recipients: Considerations and preoperative assessment strategies.

INTRODUCTION AND OBJECTIVE: Renal transplantation in the pediatric population differs from adults in many aspects. This review will focus on the unique issues of the pediatric recipient. MATERIAL AND METHODS: A narrative review on the scarce literature regarding preoperative evaluation before kidney transplantation of the paediatric recipient with an educational focus was conducted. The literature search allowed for identification of publications in English from January 2000 to October 2022. Published studies were identified by searching the following electronic databases: PubMed (MEDLINE), WHO/UNAIDS, Google-Scholar, Semantic-Scholar and Research Gate. For efficiency and reliability, recent randomized controlled trials, meta-analyses, high quality systematic reviews and large well-designed studies were used if available. Internet searches were conducted for other relevant information (definitions, policies or guidelines). RESULTS: Management of congenital urogenital anomalies and lower urinary tract dysfunction along with optimal pediatric urological preoperative assessment for renal transplantation in children is addressed in the light of the available literature. Furthermore, particular considerations including pre-emptive transplantation, transplantation of an adult-size kidney into an infant or small child is discussed. CONCLUSIONS: Outcomes of RT in children have shown progressive improvement over the past 15 years. Transplantation with living related donor gives the best results and pre-emptive transplantation provides with benefits of avoiding dialysis. Surgical and medical considerations in both the pre-transplant and post-transplant management of the pediatric kidney recipient are extremely crucial in order to achieve better short and long-term results.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

[Prostatic hyperplasia: Evaluation of practices in general practice, dissemination, and impact of recommendations]. / L'hypertrophie bénigne de prostate : évaluation des pratiques en médecine générale, diffusion et impact des recommandations.

INTRODUCTION: In 2015, the French Association of Urology, by the male lower urinary tract symptoms Committee, published a practices guideline for the management of prostatic hyperplasia in general practice. Five years after the publication of these recommendation, our objective is to assess their dissemination and their impact in general practice. MATERIAL: A specially designed questionnaire was distributed online via the departmental councils of the order and to all regional unions of liberal doctors. The distribution to general practitioners was at the discretion of each organisation depending on local policies. RESULTS: Two hundred and eighty responses were collected. Fifty-five percent of the population was female. 83 % of the general practitioners did not report having knowledge of the practice guideline. 77 % of doctors stated that they had not received training or information on prostatic hyperplasia in the past 5 years. Among the notable results, 51 % of general practitioners declared performing a digital rectal examination. 44 % prescribed an endorectal ultrasound. Only 7 % of doctors were aware of the existence of minimally invasive surgical techniques. CONCLUSION: The practices guideline for the management of prostatic hyperplasia in general practice proposed in 2015 by the male lower urinary tract symptoms Committee seems to be little known by general practitioners. Dissemination of these recommendations solely through publication in Progrès en Urologie seems ill-suited to consideration by general practitioners, and it seems necessary to consider other modes of dissemination. LEVEL OF EVIDENCE: 4, grade C.

What is the evidence for oxygenation during kidney preservation for transplantation in 2021? A scoping review.

PURPOSE: The main objective of static cold storage is to reduce cellular metabolic demands to extend the period of ischaemia prior to transplantation. Hypothermia does not halt metabolism and the absence of oxygen causes a cellular shift toward anaerobic respiratory pathways. There is emerging evidence that the introduction of oxygenation during organ preservation may help ameliorate the degree of ischaemia reperfusion injury and improve post-transplantation outcomes. This review aims to appraise and summarise all published literature that utilises oxygenation to improve kidney preservation for purposes of transplantation. METHODS: We performed a scoping review of the literature using the bibliographic databases Embase and MEDLINE. The final date for searches was 20 March 2021. All research studies included were those that reported oxygen delivery during kidney preservation as well as providing a description of the oxygenation technique. RESULTS: 17 human and 48 animal studies met the inclusion criteria. The oxygen delivery methods investigated included hypothermic oxygenated machine perfusion (HOPE), oxygen carriers, two-layer method, venous systemic persufflation, hyperbaric oxygenation, normothermic machine perfusion and sub-normothermic machine perfusion. The COMPARE trial was the only study carried out with the most methodological robustness being a randomised, double blind, controlled, phase III trial that investigated the efficacy of HOPE versus HMP. CONCLUSION: A variety of studies reflect the evolution of oxygenation with useful lessons and encouraging outcomes. The first in human studies investigating HOPE and oxygen carriers are most robustly investigated strategies for oxygenation during kidney preservation and are, therefore, the best clinical references.

Novel Organ Perfusion and Preservation Strategies in Controlled Donation After Circulatory Death in Pancreas and Kidney Transplantation.

BACKGROUND: Kidney and pancreatic transplants from controlled donation after circulatory death donors are vulnerable to ischemia-reperfusion injuries. In this context of transplant shortage, there is a need to optimize the function of these transplants and to develop novel perfusion and preservation strategies in controlled donation after circulatory death in kidney and pancreatic transplants. IN SITU PERFUSION AND PRESERVATION STRATEGIES: In situ regional normothermic perfusion improves the outcome of kidney transplants from controlled donation after circulatory death and provides equivalent results for the kidney from brain-dead donors. In situ regional normothermic perfusion is under investigation for pancreatic transplants. EX SITU PERFUSION AND PRESERVATION STRATEGIES: Perfusion on hypothermic machine perfusion is highly recommended for the kidney from controlled donation after cardiac death. Hypothermic oxygenated perfusion machine decreases the rate of graft rejection and graft failure in kidney transplantation. Ex situ normothermic perfusion is an easy way to assess renal function. In the future, kidney transplants could benefit from drug therapy during ex situ normothermic perfusion. In pancreas transplantation, hypothermic machine perfusion and ex situ normothermic perfusion present encouraging results in preclinical studies.

[Acute renal failure of the donor in encephalic death: A real contraindication to kidney transplantation?] / L'insuffisance rénale aiguë du donneur en mort encéphalique : une réelle contre-indication à la transplantation rénale ?

INTRODUCTION: The shortage of kidney transplants encourages the expansion of the limits of eligibility criteria for donation. Many donors who are brain dead display acute renal failure at the time of death; is this a real contraindication to harvesting? The aim of this study was to assess kidney graft survival from donors after brain death with confirmed acute renal failure, with or without anuria previous donation. MATERIALS AND METHODS: All of the transplants performed in two university hospitals between 2010 and 2017 were analyzed retrospectively. All patients who underwent single kidney transplant from a brain-dead donor with acute renal failure (ARF) were included in this study. ARI was defined here by a decrease over 50 % of glomerular filtration rate (GFR) to a threshold below 45mL/min/1.73 m2 at the time of kidney procurement. Kidney graft survival, incidence of delayed graft function (DGF) and the GFR at 12 months were analyzed. Analysis of kidney transplant survival based on pre-implantation biopsies was additionally done. RESULTS: One hundred and sixty four patients were transplanted with a kidney from donor with ARF during the selected period. At the admission in ICU the average GFR was 67,7±19mL/min/1,73m2. At the time of donation, the average age of donors was 56.4±17.7 years, the GFR was 33.7±8.0mL/min/1.73 m2 16 % of donors were anuric. Cold ischemia time (CIT) was 16.8±5.0hours. The average age of recipients was 55.6±14.1 years. 81 % of the cases were primary transplants. Graft function took place within 7.8±9.4 days after transplantation. There were two non-primary functions (PNF). One hundred and fifty two patients (93 %) had a functional graft at 12 months. The mean GFR at 12 months was 46.8±20.1mL/min/1.73 m2 and 122 patients (73 %) had a GFR greater than 30mL/min/1.73 m2. Seventy-one percent of preimplantation biopsies revealed acute tubular necrosis (ATU); no cortical necrosis was observed. Survival of theses grafts was 85 %, comparable to the total population of study (P=0,21) CONCLUSION: The acute renal failure of the brain-dead donor should not alone be systematically a contraindication to harvesting and kidney transplantation.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

Olmesartan-associated enteropathy: results of a national survey.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare.

Methotrexate in Crohn's disease: long-term efficacy and toxicity.

OBJECTIVE: A 16-wk, placebo-controlled trial has recently shown weekly low-dose methotrexate to be an effective treatment for patients with chronically active Crohn's disease. The long-term efficacy and safety of this antimetabolite drug, however, are not yet well established and are assessed in this study. METHODS: A total of 49 patients with Crohn's disease who were treated with methotrexate for > or =6 months were studied. All patients had been chronically treated with steroids; but at the time of initiation, only 27 were still on steroids. Of the 49 patients, 42 had previously taken azathioprine but were no longer on this drug because of intolerance or failure. Clinical remission was defined as a Harvey-Bradshaw index of <4. RESULTS: In all, 41 patients achieved complete clinical remission and were maintained on methotrexate for a median of 18 months (range, 7-59 months). In these patients the probabilities of relapse were 29%, 41%, and 48% at 1, 2, and 3 yr, respectively. A higher rate of relapse was observed in women and in patients with ileocolitis. Adverse reactions were recorded in 24 patients, requiring discontinuation of methotrexate in five. A liver biopsy was performed in 11 patients; a mild steatosis was found in five, a slight dilation of the sinusoids in one, a granulomatous hepatitis with a mild portal fibrosis in one, and a slight periportal fibrosis in one patient. CONCLUSIONS: This study suggests a long-term benefit of maintenance treatment with methotrexate in patients with chronically active Crohn's disease, with side effects that are usually only moderate.

Methotrexate for the treatment of refractory Crohn's disease.

BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.