[Improved rehabilitation after major urological surgery : what role for the general practitioner ?] / Réhabilitation améliorée après chirurgie urologique majeure : quel rôle pour le médecin généraliste ?

Enhanced recovery after surgery (ERAS) is a multimodal concept aiming to reduce surgical stress and prevent postoperative complications. Once adapted to urologic patients in 2013, this protocol evolves continuously and many international centers have now implemented it. This article resumes ERAS key principles for general practitioners as they can have a significant impact on patient's optimization before surgery.

Le protocole de réhabilitation améliorée après chirurgie est un concept de prise en charge multimodale visant à anticiper puis gérer de manière optimale le stress chirurgical inhérent à toute intervention. Adapté depuis 2013 à l'urologie, il évolue régulièrement et les centres internationaux qui appliquent ses principes sont toujours plus nombreux. Avant une chirurgie majeure, il existe un potentiel d'optimisation d'un patient auquel le généraliste peut participer activement. Cet article résume à l'attention d'un médecin généraliste les principaux points constituant cette démarche.

[Myths and reality about immunonutrition in uro-oncology]. / Immunonutrition en uro-oncologie : entre mythe et réalité.

Postoperative morbidity remains a nightmare (although vivid), both for the patient and the surgeon. One phantasmagorical idea would be to give the patient a « magic potion ¼ preoperatively aiming at eliminating the risk of postoperative complication. The purpose of the present review is to summarize the current knowledge on the potential benefits of immunonutrition administered to urological cancers patients. After a brief summary on the role of immunity in cancer surveillance and treatment, the rationale about administrating oral nutritional supplements able to modulate the patient's immune system before cystectomy for bladder cancer will be highlighted.

La survenue de complications postopératoires représente un cauchemar (bien réel), tant pour le patient que pour son chirurgien. Dès lors, quoi de plus fantasmagorique que d'administrer une « potion magique ¼ au patient avant l'intervention pour éliminer ce risque ? Le but de cet article est de résumer l'état des connaissances actuelles concernant les bénéfices potentiels, liés à l'administration d'immunonutrition aux patients traités pour cancer urologique. Après un bref rappel du rôle de l'immunité dans la surveillance et le traitement uro-oncologique, le raisonnement en faveur d'une supplémentation orale pouvant moduler le système immunitaire du patient bénéficiant d'une cystectomie pour cancer sera mis en évidence.

[Local treatment in oligometastatic urological malignancies : evidence of wishful thinking ?] / Ablation du cancer primaire dans les néoplasies urologiques oligométastatiques : évidence ou vœux pieux ?

In the past, it was generally considered that the window of curability had been missed in metastatic solid cancers. At present, novel evidence suggests that oligometastatic cancer might be amenable to a multimodal curative treatment, including ablation of the primary tumour. In this article, we summarise the indications, the controversies and future perspectives of local treatment in oligometastatic urological malignancies.

Dans le passé, on considérait le plus souvent que la fenêtre de curabilité dans les cancers solides à un stade métastatique avait été manquée. De nouvelles évidences suggèrent à présent que la maladie à un stade oligométastatique est accessible, dans certains cas, à un traitement multimodal curatif, incluant l'ablation de la tumeur primaire. Dans cet article, nous résumons les indications, les controverses ainsi que les perspectives futures du traitement local dans les cancers oligométastatiques urologiques.

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. METHODS: Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. RESULTS: Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

[Assessment and treatment of genitourinary infections]. / Bilan et traitements des infections urogénitales.

Antibiotics are most commonly prescribed for urinary bacterial infections. The purpose of this article is to review the most common infections of the genitourinary tract and to guide the choice of the most appropriate treatment. This choice depends also on the patients general state, local associated conditions and can range from observation to an emergency hospitalisation. Primary care physicians remain in the first line to take care of these patients but the urologists or the infectious disease specialists can provide some help in complex situations.

Les infections urinaires bactériennes sont l'une des principales indications à la prescription d'antibiotiques. Le but de cet article est d'aider le praticien à reconnaître les diverses infections du tractus urogénital et à les traiter en utilisant les antibiotiques de façon appropriée. Le choix du traitement dépend aussi de l'état général du patient, de conditions locales associées et peut aller de l'abstention thérapeutique à l'hospitalisation en urgence. Le médecin de famille est en première ligne dans la prise en charge de ces pathologies fréquentes et l'urologue ou l'infectiologue peuvent apporter leur contribution dans les situations complexes.

Preoperative nutritional screening by the specialist instead of the nutritional risk score might prevent excess nutrition: a multivariate analysis of nutritional risk factors.

BACKGROUND: The aim of the current study was to assess whether widely used nutritional parameters are correlated with the nutritional risk score (NRS-2002) to identify postoperative morbidity and to evaluate the role of nutritionists in nutritional assessment. METHODS: A randomized trial on preoperative nutritional interventions (NCT00512213) provided the study cohort of 152 patients at nutritional risk (NRS-2002 ≥3) with a comprehensive phenotyping including diverse nutritional parameters (n=17), elaborated by nutritional specialists, and potential demographic and surgical (n=5) confounders. Risk factors for overall, severe (Dindo-Clavien 3-5) and infectious complications were identified by univariate analysis; parameters with P<0.20 were then entered in a multiple logistic regression model. RESULTS: Final analysis included 140 patients with complete datasets. Of these, 61 patients (43.6%) were overweight, and 72 patients (51.4%) experienced at least one complication of any degree of severity. Univariate analysis identified a correlation between few (≤3) active co-morbidities (OR=4.94; 95% CI: 1.47-16.56, p=0.01) and overall complications. Patients screened as being malnourished by nutritional specialists presented less overall complications compared to the not malnourished (OR=0.47; 95% CI: 0.22-0.97, p=0.043). Severe postoperative complications occurred more often in patients with low lean body mass (OR=1.06; 95% CI: 1-1.12, p=0.028). Few (≤3) active co-morbidities (OR=8.8; 95% CI: 1.12-68.99, p=0.008) were related with postoperative infections. Patients screened as being malnourished by nutritional specialists presented less infectious complications (OR=0.28; 95% CI: 0.1-0.78), p=0.014) as compared to the not malnourished. Multivariate analysis identified few co-morbidities (OR=6.33; 95% CI: 1.75-22.84, p=0.005), low weight loss (OR=1.08; 95% CI: 1.02-1.14, p=0.006) and low hemoglobin concentration (OR=2.84; 95% CI: 1.22-6.59, p=0.021) as independent risk factors for overall postoperative complications. Compliance with nutritional supplements (OR=0.37; 95% CI: 0.14-0.97, p=0.041) and supplementation of malnourished patients as assessed by nutritional specialists (OR=0.24; 95% CI: 0.08-0.69, p=0.009) were independently associated with decreased infectious complications. CONCLUSIONS: Nutritional support based upon NRS-2002 screening might result in overnutrition, with potentially deleterious clinical consequences. We emphasize the importance of detailed assessment of the nutritional status by a dedicated specialist before deciding on early nutritional intervention for patients with an initial NRS-2002 score of ≥3.

[Gender disparities in urologic cancers]. / Inégalité des sexes face au cancer en urologie.

The purpose of the present review is to summarize the current knowledge on the impact of gender on urological cancers. There is a discrepancy in the incidence of urothelial and kidney cancers, with a higher prediction for male patients. Men have a three-times greater risk of developing bladder cancer compared to women, but female gender has been identified as an independent adverse prognostic factor for both disease recurrence and progression. At diagnosis, men with renal cell carcinoma present more often with larger tumors and higher stage and grade disease compared to females. Smoking habits, tumor biology, sex steroid hormones, genetic differences and social behavior may be the main drivers of gender disparities. Therefore, the inclusion of this variable in validated prognostic tables and nomograms should be concretely discussed.

[Urology]. / Urologie.

This article is addressed to general practitioners and summarizes some of the latest developments in urology. Recent advances in screening, diagnosis and medical as well as surgical treatments of common urological diseases are reviewed.

[Prostate biopsy: which strategy for which patient?]. / Biopsies de la prostate en 2015: quelle biopsie pour quel patient?

The adoption of multiparametric MRI within the diagnostic pathway has allowed urologists to move from random biopsy to targeted biopsy directed towards MR-visible lesions. The use of software for MR to TRUS fusion may enhance the diagnostic accuracy of targeted biopsy. To determine the eligibility for tissue-preserving approaches, further precision is required, and template prostate mapping biopsy may be offered. The employment of novel biopsy techniques provide better characterisation of the disease, and allows a tailored approach to a single subject.

[Focal therapy in prostate cancer: rationale, results and perspectives]. / Thérapie focale du cancer de la prostate: rationnel, résultats et perspectives.

Focal therapy is a novel treatment strategy in prostate cancer aiming to treat only the area of the gland harbouring clinically significant disease. The overall objective is to maintain the oncological benefit of active treatment while minimising treatment-related morbidity. Leading centres are currently evaluating various minimally invasive technologies in a rigorous manner. Oncological and functional results in mid-term are encouraging with low rate of urinary incontinence and erectile dysfunction. However, the oncological outcome needs to be evaluated in the long-term in the light of the prolonged natural history of the disease.

Impact of Enhanced Recovery after Surgery® Protocol Compliance on Length of Stay, Bowel Recovery and Complications after Radical Cystectomy.

BACKGROUND: Despite existing standardized surgical techniques and the development of new perioperative care protocols, radical cystectomy (RC) morbidity remains a serious challenge for urologists. Postoperative ileus (POI) is one of the most common postoperative complications, often leading to a longer length of stay (LOS). The aim of our study was to assess the impact of compliance to the Enhanced Recovery After Surgery (ERAS®) protocol on bowel recovery, 30-day complications and LOS after RC for bladder cancer (BC). METHODS: Data from consecutive patients undergoing RC for BC within an ERAS® dedicated protocol were analyzed. Exclusion criteria were urinary diversion other than ileal conduit and palliative RC. Patients were divided into two groups according to their compliance (A: low-compliance and B: high-compliance). ERAS® compliance was extracted from the ERAS® Interactive Audit System (EIAS) database. Postoperative complications were prospectively recorded by a dedicated study nurse 30 days after RC. POI was defined as the placement of a nasogastric tube. Logistic regression analysis was used to identify predictors of 30-day complications and POI. RESULTS: After considering the exclusion criteria, 108 patients were included for the final analysis. The median global compliance to the ERAS® protocol was 61%. A total of 78 (72%) patients had a compliance <65% (group A), while the remaining 30 (28%) had a compliance >65% (group B). No significant differences were found among the two groups regarding the 30-day complication rate (86% in group A versus 73% in group B, p = 0.82) and LOS (14 days in group A versus 15 days in group B, p = 0.82). The time to stool was significantly shorter in group B (4 days versus 6 days, p = 0.02), and the time to tolerate solid food was slightly faster in group B but not significant (8 versus 7 days, p = 0.23). The POI rate was significantly lower in patients with a higher ERAS® compliance (20% versus 46%, p = 0.01). A multivariate analysis showed that ERAS® compliance was not significantly associated with 30-day total complications. However, a lower compliance to the ERAS® protocol and age > 75 years were significant independent predictors of POI. CONCLUSIONS: Our study provides further evidence to support the beneficial effect of the ERAS® protocol in patients undergoing RC, particularly in terms of facilitating a faster recovery of bowel function and preventing POI. Future research should focus on investigating novel approaches and interventions to improve compliance with the ERAS® protocol. This may involve patient education, multidisciplinary teamwork, and continuous quality improvement initiatives.

The role of preoperative immunonutrition on morbidity and immune response after cystectomy: protocol of a multicenter randomized controlled trial (INCyst Trial).

INTRODUCTION: Cancer, malnutrition, and surgery negatively impact patient's immune system. Despite standardized surgical technique and the development of new perioperative care protocols, morbidity after cystectomy remains a serious challenge for urologists. Most common postoperative complications, such as infections and ileus, often lead to longer length of stay and worse survival. The immune system and its interaction with the gut microbiota play a pivotal role in cancer immunosurveillance and in patient's response to surgical stress. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN) may improve the nutritional status, immunological function, and clinical outcome of surgical patients. Aims of the study are (1) to evaluate the impact of IN on morbidity and mortality at 30 and 90 days after cystectomy and (2) to determine immune and microbiota signature that would predict IN effect. METHODS: This is a randomized, multicentric, controlled, pragmatic, parallel-group comparative study, supported by the Swiss National Science Foundation. A total of 232 patients is planned to be enrolled between April 2023 and June 2026. Three participating centers (Lausanne, Bern, and Riviera-Chablais) have been selected. All patients undergoing elective radical and simple cystectomy will be randomly assigned to receive 7 days of preoperative IN (Oral Impact®, Nestlé, Switzerland) versus standard of care (control group) and followed for 90 days after surgery. For the exploratory outcomes, blood, serum, urine, and stool samples will be collected in patients treated at Lausanne. In order to determine the impact of IN on immune fitness, patients enrolled at Lausanne will be vaccinated against influenza and the establishment of the vaccine-specific immune response will be followed. Analysis of the microbiota and expression of argininosuccinate synthetase 1 as potential biomarker will also be performed. DISCUSSION AND CONCLUSION: Strengths of the INCyst study include the randomized, multicenter, prospective design, the large number of patients studied, and the translational investigation. This study will challenge the added value of preoperative IN in patients undergoing cystectomy, assessing the clinical effect of IN on the onset of postoperative morbidity and mortality after cystectomy. Furthermore, it will provide invaluable data on the host immune response and microbiota composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT05726786. Registered on March 9, 2023.

Are patients at nutritional risk more prone to complications after major urological surgery?

PURPOSE: The nutritional risk score is a recommended screening tool for malnutrition. While a nutritional risk score of 3 or greater predicts adverse outcomes after digestive surgery, to our knowledge its predictive value for morbidity after urological interventions is unknown. We determined whether urological patients at nutritional risk are at higher risk for complications after major surgery than patients not at nutritional risk. MATERIALS AND METHODS: We performed a prospective observational study in consecutive patients undergoing major surgery. A priori sample calculation resulted in a study cohort of 220 patients. Interim analysis was planned after 110 patients. The nutritional risk score was assessed preoperatively by a specialized study nurse. Nutritional care was standardized in all patients. Postoperative complications were defined previously using the standardized Dindo-Clavien classification. The primary end point was 30-day morbidity. Univariate and multivariate analysis was performed to identify predictors of complications. RESULTS: The study was discontinued due to significant results after interim analysis. A total of 125 patients were included in analysis from June 2011 to June 2012 and 15 were excluded because of incomplete data. Of 51 patients at nutritional risk 38 (74%) presented with at least 1 complication compared to 28 of 59 controls (47%). Patients at nutritional risk were at threefold risk for complications on univariate and multivariate analysis (OR 3.3, 95% CI 1.3-8.0). Cystectomy was the only other predictor of morbidity (OR 10, 95% CI 2-48). CONCLUSIONS: Patients at nutritional risk are more prone to complications after major urological procedures. Whether this increased morbidity can be reversed by perioperative nutritional support should be studied.

[Enhanced recovery after surgery applied to cystectomy patients]. / Rétablissement postopératoire optimisé, applique aux patients après cystectomie.

Enhanced Recovery After Surgery (ERAS) is a multimodal concept combining pre, intra and postoperative evidence-based care elements to reduce surgical stress. ERAS pathways have been shown to significantly reduce morbidity, length of hospital stay and total costs when applied to colorectal surgery. It is therefore considered standard of care in this specialty. There can be no doubt that ERAS principles can be applied also in other major surgeries. However, uncritical application of the guidelines issued from colonic procedures seems inappropriate as the surgical procedures in pelvic cancer surgery differ considerably. This article reports on the first steps of an ERAS project and his introduction in urology.

ERAS® protocol improves survival after radical cystectomy: A single-center cohort study.

INTRODUCTION: To evaluate Enhanced recovery after surgery (ERAS®) protocol on oncological outcomes for patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). METHODS: A prospectively maintained single-institutional database comprising 160 consecutive UCB patients who underwent open RC from 2012 to 2020 was analyzed. Patients receiving chemotherapy and those with a urinary diversion other than ileal conduit were excluded. Patients were divided into two groups according to the perioperative management (ERAS® and pre-ERAS®). The study aimed to evaluate the impact of the ERAS® protocol on survival at five years after surgery using a Kaplan-Meier log-rank test. A multivariable Cox proportional hazards model was used to identify prognostic factors for cancer-specific (CSS) and overall survival (OS). RESULTS: Of the 107 patients considered for the final analysis, 74 (69%) were included in the ERAS® group. Median follow-up for patients alive at last follow-up was 28 months (interquartile range [IQR] 12-48). Five-years CSS rate was 74% for ERAS® patients, compared to 48% for the control population (P = 0.02), while 5-years OS was 31% higher in the ERAS® (67% vs. 36%, P = .003). In the multivariable analysis, ERAS® protocol and tumor stage were independent factors of CSS, while ERAS®, tumor stage so as total blood loss were independent factors for OS. DISCUSSION: A dedicated ERAS® protocol for UCB patients treated with RC has a significant impact on survival. Reduction of stress after a major surgery and its potential improvement of perioperative patient's immunity may explain these data.

Ex vivo ultrasound control of resection margins during partial nephrectomy.

PURPOSE: Surgery remains the treatment of choice for localized renal neoplasms. While radical nephrectomy was long considered the gold standard, partial nephrectomy has equivalent oncological results for small tumors. The role of negative surgical margins continues to be debated. Intraoperative frozen section analysis is expensive and time-consuming. We assessed the feasibility of intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy and its correlation with margin status on definitive pathological evaluation. MATERIALS AND METHODS: A study was done at 2 institutions from February 2008 to March 2011. Patients undergoing partial nephrectomy for T1-T2 renal tumors were included in analysis. Partial nephrectomy was done by a standardized minimal healthy tissue margin technique. After resection the specimen was kept in saline and tumor margin status was immediately determined by ex vivo ultrasound. Sequential images were obtained to evaluate the whole tumor pseudocapsule. Results were compared with margin status on definitive pathological evaluation. RESULTS: A total of 19 men and 14 women with a mean ± SD age of 62 ± 11 years were included in analysis. Intraoperative ex vivo ultrasound revealed negative surgical margins in 30 cases and positive margins in 2 while it could not be done in 1. Final pathological results revealed negative margins in all except 1 case. Ultrasound sensitivity and specificity were 100% and 97%, respectively. Median ultrasound duration was 1 minute. Mean tumor and margin size was 3.6 ± 2.2 cm and 1.5 ± 0.7 mm, respectively. CONCLUSIONS: Intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy is feasible and efficient. Large sample studies are needed to confirm its promising accuracy to determine margin status.

Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.

The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes, mTORC1 and mTORC2 plays an important role in tumor growth. Whereas the role of mTORC1 has been well characterized in this process, little is known about the functions of mTORC2 in cancer progression. In this study, we explored the specific role of mTORC2 in colon cancer using a short hairpin RNA expression system to silence the mTORC2-associated protein rictor. We found that downregulation of rictor in HT29 and LS174T colon cancer cells significantly reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice xenograft model. Taken together, these results show that the inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting mTORC2 may provide a novel treatment strategy for colorectal cancer.

[Benefits of ultrasonography in kidney and testicular-sparing surgery]. / Apport de l'utltrasonographie dans la chirurgie d'épargne du rein et du testicule.

Renal and testicular cancers account for 4% and 1% of all malignancies, respectively. Their prevalence has increased over the past years and is related to the widespread use of medical imaging and the incidental findings of small asymptomatic tumors on computed tomography scanners and ultrasounds examinations. The urologist faces the dilemma of overtreating benign asymptomatic lesions with radical surgery. Therefore, organ-sparing surgery was developed. Recent studies have shown that recurrence rates are often similar between organ-sparing and radical surgery for small kidney or testicular tumors. However, the risk of positive surgical margins consecutive to organ-sparing surgery remains a matter of debate. This article discusses the role of ex-vivo peroperative ultrasonography in predicting negative surgical margins during kidney- and testicular-sparing surgery.

Intramuscular Immunization Induces Antigen-specific Antibodies in Urine.

Towards the development of vaccines against urinary tract infections (UTI), we determined the ability of intramuscular (i.m.) immunization to result in antigen-specific antibodies in urine. As a model antigen/vaccine, levels of total and vaccine-specific antibodies were determined in urine as a spin-out study of a phase 1 trial. Non-muscle-invasive bladder cancer (NMIBC) patients at different risks of progression, undergoing intravesical bacillus Calmette-Guérin (BCG) immunotherapy or not, received an adjuvanted recombinant protein vaccine that resulted in high titers of vaccine-specific serum immunoglobulin G (IgG) in all patients, regardless of the risk group. Vaccine-specific IgG and immunoglobulin A (IgA) were detected in urine of half of the patients at low risk of progression NMIBC and in all the intermediary/high- (int/high) risk patients. Vaccine-specific IgG titers were correlated to total urinary IgG levels, the latter being higher in the int/high-risk patients. In contrast, vaccine-specific IgA did not correlate to urinary IgA levels. Furthermore, vaccine-specific antibodies were transiently increased by intravesical BCG instillations. Altogether, our data show that a standard i.m. immunization can effectively induce antigen-specific antibodies in urine, which, upon selection of optimal vaccine targets, may provide protection against UTI. Vaccine-specific IgG titers were dependent on conditions affecting total urinary IgG levels, while production of vaccine-specific IgA in situ might independently contribute to protection against infections in the bladder. PATIENT SUMMARY: Towards the development of vaccines able to protect against urinary tract infections, we examined the potential of the intramuscular vaccination using a model antigen. We found two types of specific antibodies in the urine, which together may locally contribute to protection against infections, thus supporting the use of such a standard immunization route.