Upper urinary tract disease: what we know today and unmet needs

PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare and poorly investigated disease. Intense collaborative efforts have increased our knowledge and improved the management of the disease. The objective of this review was to discuss recent advances and unmet needs in UTUC. METHODS: A non-systematic Medline/PubMed literature search was performed on UTUC using the terms "upper tract urothelial carcinoma" with different combinations of keywords. Original articles, reviews and editorials in English language were selected based on their clinical relevance. RESULTS: UTUC is a disease with specific epidemiologic and risk factors different to urothelial carcinoma of the bladder (UCB). Similarly to UCB, smoking increases the risk of UTUC and worsens its prognosis, whereas aristolochic acid (AA) exposure and mismatch repair genes abnormality are UTUC specific risk factors. A growing understanding of biological pathways involved in the tumorigenesis of UTUC has led to the identification of promising prognostic/predictive biomarkers. Risk stratification of UTUC is difficult due to limitations in staging and grading. Modern imaging and endoscopy have improved clinical decision-making, and allowed kidney-sparing management and surveillance in favorable-risk tumors. In high-risk tumors, radical nephroureterectomy (RNU) remains the standard. Complete removal of the intramural ureter is necessary with inferiority of endoscopic management. Post-RNU intravesical instillation has been shown to decrease bladder cancer recurrence rates. While the role of neoadjuvant cisplatin based combination chemotherapy and lymphadenectomy are not clearly established, the body of evidence suggests a survival benefit to these. There is currently no evidence for adjuvant chemotherapy (AC) in UTUC. CONCLUSIONS: Despite growing interest and understanding of UTUC, its management remains challenging, requiring further high quality multicenter collaborations. Accurate risk estimation is necessary to avoid unnecessary RNUs while advances in technology are still required for optimal kidney-sparing approaches

Influence of statin use on clinicopathological characteristics of localized prostate cancer and outcomes obtained after radical prostatectomy: a single center study

To assess the impact of statin use on biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP)

Évaluation des compétences pratiques en fin de deuxième cycle des études médicales : exemple du drainage du bas appareil urinaire

IntroductionLe drainage vésical peut, mal pratiqué, être iatrogène en se compliquant notamment d’infections et de traumatismes de l’appareil urinaire. Cette étude a pour objectif de déterminer la capacité des étudiants en médecine de fin de deuxième cycle à pratiquer les différents moyens de drainage des urines. Matériel et méthodes Entre janvier et mars 2007, un questionnaire d’autoévaluation des compétences de drainage urinaire a été envoyé par mail à un échantillon représentatif d’étudiants en médecine en dernière année d’externat, soit deux mois avant l’épreuve de l’examen national classant. Résultats Deux cent soixante-dix-sept réponses ont été reçues et analysées. Soixante-douze étudiants (26 %) jugeaient qu’ils maîtrisaient le cathétérisme urétrovésical chez l’homme et 106 étudiants (38,3 %) chez la femme à la fin de leur externat. Soixante et onze étudiants sur les 277 (25,5 %) avaient effectué un stage en urologie au cours de leur cursus. Parmi eux, 53,5 % estimaient acquis le sondage à demeure (SAD) chez l’homme (p < 0,001) et 39 (54,9 %) chez la femme (p < 0,001). Soixante-treize étudiants (26,4 %) estimaient qu’ils maîtrisaient le sondage minute d’une femme ou d’un homme et un seul considérait la pose de cathéter sus-pubien comme acquis. Conclusion L’apprentissage des gestes de drainage urinaire est enseigné de façon inappropriée au cours des études médicales puisque de jeunes médecins se sentent incapables de les reproduire au terme de leur externat. Cela est critiquable, car le sondage doit pouvoir être réalisé par tous médecins non urologues dans leur pratique quotidienne, notamment en terrain hospitalier. Cette étude doit mener à une réflexion sur l’amélioration de l’enseignement des gestes pratiques médicaux essentiels pendant l’externat

Evidence-based medicine et étudiants en médecine français : état des lieux

IntroductionL’Evidence-Based Medicine (EBM) est indispensable à l’exercice de la médecine. Notre objectif était de connaître quel en était son niveau de connaissance par les étudiants français. Matériel et Méthodes Entre avril et mai 2008, un questionnaire a été envoyé par courriel à 900 étudiants en dernière année du deuxième cycle des études médicales participant à des conférences publiques ou privées d’internat. Résultats Sur les 327 réponses, 297 (91 %), 94 (29 %) et 85 (26 %) étudiants déclaraient savoir lire, écrire et parler l’anglais médical. Quatre-vingt-dix étudiants (28 %) lisaient un article d’une revue médicale française, une fois par mois et 43 (13 %) lisaient un article d’une revue médicale internationale une fois par mois. Trois cent onze (95 %) connaissaient les bases de recherche médicale sur Internet et 219 (67 %) les utilisaient. Vingt-quatre (7 %) avaient déjà participé à la rédaction d’un article médical, sept (2 %) avait été co-auteurs. Deux cent soixante-douze (83 %) avait réalisé une présentation orale lors d’un staff médical et trois (1 %) lors d’un congrès. Enfin, 237 (73 %) comprenaient l’intérêt de l’épreuve d’analyse critique d’article à l’examen national classant (ECN) et 70 (21 %) pensaient y être préparés. Conclusion L’insuffisance de l’apprentissage de l’EBM est une des limites du système de formation français. L’introduction de la lecture critique d’article (LCA) à l’ECN est un début de réponse concret à ce problème

Consultation on UTUC, Stockholm 2018 aspects of risk stratification: long-term results and follow-up

Purpose: To summarize current knowledge on upper urinary tract carcinoma (UTUC) regarding risk stratification, long-term results, and follow-up. Methods: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC, September 2018, Stockholm. Results: To optimize oncological outcome considering both cancer-specific survival (CSS) and overall survival (OS), it is essential to identify pre- and postoperative prognostic factors. In low-risk UTUC, kidney-sparing surgery (KSS) and radical nephroureterectomy (RNU) offer equivalent CSS, whereas RNU may result in poorer OS due to nephron loss. For more aggressive tumours, undergrading can lead to insufficient treatment. The strongest prognostic factors are tumour stage and grade. Determining grade is best achieved by ureterorenoscopy (URS) with focal samples, biopsy and cytology. Staging is more difficult but can be indirectly achieved by multiphase computed tomography urography (CTU) or tumour grade determined by cytology and histopathology. Patients treated with KSS should be monitored closely with regular follow-ups (URS and CTU). Conclusion: KSS should be offered in low-risk UTUC when feasible, whereas RNU is the treatment of choice in organ-confined high-risk UTUC. Intravesical recurrence (IVR) is common after RNU, but a single postoperative dose of mitomycin instillation decreases IVR. Endourological management has high local and bladder recurrence rates; however, its effect on CSS or overall survival OS is unclear. RNU is associated with significant risk of chronic kidney disease. Careful selection of patients and risk stratification are mandatory, and patients should be followed according to strict protocols

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy

Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone

Outcomes of surgical treatment for upper urinary tract transitional cell carcinoma: Comparison of retroperitoneoscopic and open nephroureterectomy

<p>Abstract</p> <p>Objectives</p> <p>To determine the surgical and oncologic outcomes in patients who underwent retroperitoneoscopic nephroureterectomy (RNU) in comparison to standard open nephroureterectomy (ONU) for upper urinary tract transitional cell carcinoma (TCC).</p> <p>Patients and methods</p> <p>From April 2001 to January 2007, 60 total nephroureterectomy were performed for upper tract TCC at Siriraj Hospital. Of the 60 patients, thirty-one were treated with RNU and open bladder cuff excision, and twenty-nine with ONU. Our data were reviewed and analyzed retrospectively. The recorded data included sex, age, history of bladder cancer, type of surgery, tumor characteristics, postoperative course, disease recurrence and progression.</p> <p>Results</p> <p>The mean operative time was longer in the RNU group than in the ONU group (258.8 versus 190.6 min; p = 0. < 001). On the other hand, the mean blood loss and the dose of parenteral analgesia (morphine sulphate) were lower in the RNU group (289.3 versus 313.7 ml and 2.05 versus 6.72 mg; p = 0.868 and p = 0.018, respectively). There were two complications in each group. No significant difference in p stage and grade in both-groups (p = 0.951, p = 0.077). One patient with RNU had lymph node involvement, three in ONU. Mean follow up was 26.4 months (range 3–72) for RNU and 27.9 months (range 3–63) for ONU. No port metastasis occurred during follow up in RNU group. Tumor recurrence developed in 11 patients (bladder recurrence in 9 patients, local recurrence in 2 patients) in the RNU group and 14 patients (bladder recurrence in 13 patients, local recurrence in 1 patient) in the ONU group. No significant difference was detected in the tumor recurrence rate between the two procedures (p = 0.2716). Distant metastases developed in 3 patients (9.7%) after RNU and 2 patients (6.9%) after ONU. The 2 year disease specific survival rate after RNU and ONU was 86.3% and 92.5%, respectively (p = 0.8227).</p> <p>Conclusion</p> <p>Retroperitoneoscopic nephroureterectomy is less invasive than open surgery and is an oncological feasible operation. Thus, the results of our study supported the continued development of laparoscopic technique in the management of upper tract TCC.</p