Les progrès continus de la recherche scientifique dans le domaine de la santé ont entraîné une augmentation de l'espérance et de la qualité de vie. Ainsi, le développement de nouveaux médicaments et des dispositifs médicaux a permis d'améliorer les conditions sanitaires et la prise en charge des patients au prix d'une inflation des dépenses de santé. Ces évolutions ont eu pour conséquences d'inciter les états à mettre en place des procédures d'évaluation de l'efficacité et de la gestion des risques liés à ces nouvelles approches thérapeutiques. Plus récemment, les restrictions budgétaires liées à la crise économique dans de nombreux pays de l'OCDE ont contraint les états à diminuer la part de leur budget consacré à la santé. Cette situation les a conduits à mettre en place des politiques de santé basées sur l'optimisation des ressources.En ce sens, l'évaluation médico-économique et la pharmaco-épidémiologie constituent pour les acteurs de santé et pour les décideurs politiques un outil d'analyse décisionnelle particulièrement légitime. Ils sont aujourd'hui de plus en plus intégrés dans les réflexions sur les stratégies de soins et dans la mise en place des programmes de santé. L'objectif de notre travail de recherche a été à travers deux projets, d'étudier l'intérêt de l'évaluation médico-économique et de la pharmaco-épidémiologie en chirurgie pédiatrique. Ainsi, dans une première partie plus théorique, une synthèse des différentes études de pharmaco-économie, de pharmaco-épidémiologie a été conduite et un état des lieux des études d'évaluation médico-économiques dans la chirurgie de l'enfant a été réalisé. Dans une seconde partie plus pratique, les deux projets concernant la chirurgie pédiatrique sont présentés :- Le projet 1 (pharmaco-économie) présente l'évaluation et l'analyse coût-efficacité dutraitement du reflux vésico-urétéral de grade modéré chez l'enfant.- Le projet 2 (pharmaco-épidémiologie) est une étude multicentrique prospective surl'épidémiologie de l'invagination intestinale aiguë de moins de 1 an (EPIstudy) / The continuing progress of scientific research in the field of health have led to increasingexpectancy and quality of life. Thus, the development of new medicines and medical deviceshave improved the health conditions and treatment of patients at the cost of inflation inhealth spending. These developments have effects for encouraging states to implementprocedures of effectiveness assessment and management of risks associated with these newtherapeutic approaches.More recently, budget cuts due to the economic crisis in many OECD countries havecompelled states to reduce the proportion of their budgets on health. This led them todevelop health policies based on resource optimization.In this sense, the health econoic evaluation and pharmacoepidemiology are for healthcarestakeholders and policy makers a tool for decisional analysis. They are now increasingly integrated into reflection on care strategies and the implementation of health programs. The objective of our research has been through two projects, to study the interest of the health economic evaluations and pharmacoepidemiology in pediatric surgery. Thus, in a first, theoretical part, it is a synthesis of various studies of pharmaco-economics, pharmacoepidemiology was conducted and an inventory of economic evaluation studies in pediatric surgery was performed. In the second part more convenient, both projects are presented in pediatric surgery :- Project 1 (pharmacoeconomic) presents evaluation and cost-effectiveness analysis oftreatment of moderate grade of vesicoureteral reflux in children.- Project 2 (Parmacoepidemiology) is a prospective multicenter study of theepidemiology of acute intussusception among infants (EPIstudy)

Hydronephrosis, due to ureteropelvic junction obstruction, is a common condition in infants with an incidence of approximately 0.5-1%. During the last decade, the surgical management of non-symptomatic hydronephrosis has become more conservative, and the long-term physiological consequences of this new policy are unclear. The overall aim of this thesis was to determine whether there is a link between hydronephrosis and the development of hypertension. Hydronephrosis was induced by partial ureteral obstruction in 3-week old rats or mice. In the adult animals, blood pressure was measured telemetrically during different sodium conditions and the renal function was evaluated. Both species developed salt-sensitive hypertension and histopathological changes (i.e. fibrosis, inflammation, glomerular and tubular changes) that correlated with the degree of hydronephrosis. An abnormal renal excretion pattern with increased diuresis and impaired urine concentrating ability was observed in hydronephrosis. The mechanisms were primarily located to the diseased kidney, as relief of the obstruction attenuated blood pressure and salt-sensitivity. Increased renin angiotensin system activity, due to ureteral obstruction, might be involved in the development but not necessary the maintenance of hypertension. Hydronephrotic animals displayed reduced nitric oxide availability, which might be due to increased oxidative stress in the diseased kidney. Renal nitric oxide deficiency and subsequent resetting of the tubuloglomerular feedback mechanism, appeared to have an important role in the development of hypertension. In conclusion, experimental hydronephrosis, induced by partial ureteral obstruction, provides a new model for studies of salt-sensitive hypertension. Furthermore, the new findings imply that the current conservative treatment strategy in hydronephrosis should be reconsidered in favour of treatment that is more active, in order to prevent the development of renal injury and hypertension in later life.

Σκοπος της μελέτης είναι να συγκρίνει τις απλές μεταλλικές ενδοπροθέσεις (stents) με τις εσωτερικά και εξωτερικά επικαλυπτόμενες μεταλλικές ενδοπροθέσεις σε πειραματόζωο χοίρο. Τοποθετήθηκαν μεταλλικά stents σε 9 θηλυκούς χοίρους που ζύγιζαν 25-30 κιλά. Τοποθετήθηκαν stent σε 18 ουρητήρες είτε στον δεξιό είτε στον αριστερό ουρητήρα. Σε έξι ουρητήρες τοποθεητήθηκε ενδοπρόθεση Wallstent (Schneider,Zurich,Switzerland)σε έξι τοποθετήθηκε Passager stent (Βoston Scientific, Natick,MA,USA)και σε έξι Corvita endoluminal graft- CEG(Boston Scientific, Natick, MA, USA). Εγινε έλεγχος της βατότητας με νεφροστομογραφία 24ώρες και 21ημέρες μετά την τοποθέτηση. Σε τεσσερεις περιπτώσεις το Passager stent μετανάστευσε στην ουροδόχο κύστη με αποτέλεσμα την ουρητηρική απόφραξη. Σε όλες τις άλλες περιπτώσεις η ροή των ούρων ήταν φυσιολογική. Το Wallstent stent προκάλεσε ήπια φλεγμονώδη αντίδραση και μεταπλασία του ουροθηλίου; Το CEG stent πιο έντονη αντίδραση και τέλος την πίο έντονη φλεγμονώδη αντίδραση προκάλεσε το Passager stent με συνοδό νέκρωση του ουροθηλίου. Τα επικαλλυμένα stents δεν εμφάνισαν ουροθηλιακή υπερπλασία στην έσω επιφάνεια του stent. Τα πειραματικά αποτελέσματα δείχνουν ότι το απλό Wallstent stent προκαλεί λιγότερη φλεγμονώδη αντίδραση των παρακείμενων ιστών σε σύγκριση με τα επικαλλυμένα stents. Απο την αλλη πλευρά τα επικαλυπτόμενα stents περιορίζουν σημaντικά την ουροθηλιακή υπερπλασία αλλα έχουν την τάση να μεταναστεύουν προς την ουροδόχο κύστη. / We report out experience with the use of metallic self expandable and balloon expandable stents for the treatment of malignant ureteral obstruction. We treated 12 consecutive patients with malignant ureteral obstruction, for a total of 14 ureters with stents placed. We placed metallic balloon exspandable stents in 6 patients and self-expandable metallic stents in the remaining 6. mean patient age was 65 years and mean followup was 9 months.(range 8 to 16). Of the ureters 11 were patent without any additional manipulations during the followup of 8 to 16 months. Secondary interventions were needed in 3 cases because of obstructive urothelial hyperplastic reaction,tumor ingrowth and local recurrence of the primary cancer invading the upper end of the stent. Two patients died 2 and 10 months after placement of the stent. Both types of metal stents have advantages and disadvantages that must be balanced against each other when choosing the ideal device for the treatment of obstruction. Implantation of a metal self-expanding or balloon expanding stent is safe and effective for the palliative treatment of malignant ureteral obstruction in late stage cancer patient.

Οι εμποτισμένες με φάρμακα μεταλλικές ενδοπροθέσεις (DES) έχει αποδειχθεί ότι ελαχιστοποιούν την υπερπλασία του ενδοθηλίου των στεφανιαίων αγγείων. Η υπερπλαστική αντίδραση του ουροθηλίου είναι το πιο συχνή επιπλοκή της χρήσης των μεταλλικών ενδοπροθέσεων στον ουρητήρα. Στην παρούσα μελέτη αξιολογήσαμε τις εμποτισμένες με zotarolimus μεταλλικές ενδοπροθέσεις (ZES- Endeavor Resolute, Medtronics Inc, USA) στον ουρητήρα χοίρων και κουνελιών. Μέθοδος: Μία ZES and μία συνήθης μεταλλική ενδοπρόθεση (BMS) τοποθετήθηκαν στον κάθε ουρητήρα 10 χοίρων και 6 κουνελιών. Η τοποθετήση έγινε κυστεοσκοπικά. Αξονική τομογραφία (CT) έγινε για την αξιολόγηση των ουρητήρων του χοίρου και ενδοφλέβιος πυελογραφία (IVP) έγινε για τον ίδιο σκοπό στα κουνέλια. Το πρόγραμμα παρακολούθησης περιλάμβανε CT ή IVP κάθε εβδομάδα για τις επόμενες 4 εβδομάδες για τους χοίρους και 8 εβδομάδες για τα κουνέλια. Σπινθηρογραφήματα νεφρών πριν την τοποθέτηση των ενδοπροθέσεων και κατά την 3 εβδομάδα παρακολούθησης έλαβε χώρα σε όλα τα ζώα. Οπτική τομογραφία συνοχής (OCT) χρησιμοποιήθηκε για την εκτίμηση της κατάστασης του αυλού και τοιχώματος των ουρητήρων που έφεραν τις ενδοπροθέσεις. Ιστοπαθολογική εξέταση των ουρητήρων με τις ενδοπρόθεσεις έγινε με τα παρασκευάσματα να έχουν στερεοποιηθεί σε glycol-methacrylate ρητίνη. Αποτελέσματα: Υπερπλαστική αντίδραση διαπιστώθηκε και στους δύο τύπους ενδοπροθέσεων. Οι BMS ενδοπροθέσεις αποφράχτηκαν πλήρως σε 7 ουρητήρες χοίρων ενώ οι ουρητήρες των ιδίων ζώων που έφεραν ZES ενδοπρόθεση έφεραν υπερπλαστική αντίδραση αλλά δεν κατέληγαν σε απόφραξη. Δύο ουρητήρες κουνελιών με BMS ενδοπροθέσεις αποφράχτηκαν τελείως ενώ όλες οι ZES ενδοπροθέσεις δε συσχετίστηκαν με απόφραξη του ουρητήρα. Διαπιστώθηκε έκπτωση της λειτουργίας 7 νεφρών χοίρων και 2 κουνελιών που είχαν ουρητήρες με αποφραγμένες ενδοπροθέσεις. Η OCT έδειξε αυξημένη υπερπλαστική αντίδραση σε ουρητήρες που έφεραν BMS ενδοπρόθεση σε σχέση με ZES. Παρόλα αυτά, η ιστοπαθολογική εξέταση έδειξε υπερπλαστική αντίδραση παρούσα σε όλες τις ενδοπροθέσεις αλλά σημαντικά περισσότερη υπερπλαστική αντίδραση στις BMS ενδοπροθέσεις. Συμπέρασμα: Οι ZES ενδοπροθέσεις στους ουρητήρες χοίρων και κουνελιών δε συσχετίστηκαν με υπερπλαστική αντίδραση που οδηγούσε σε απόφραξη της ενδοπρόθεσης. Αυτές οι ενδοπροθέσεις συσχετίστηκαν με σημαντικά μικρότερη υπερπλαστική αντίδραση συγκριτικά με τις BMS ενδοπροθέσεις ενώ η φλεγμονώδης αντίδραση ήταν παρόμοια και στους δύο τύπους ενδοπροθέσεων. / Drug eluting stents (DES) proved to minimize neointimal hyperplasia in coronary vessels. Hyperplastic reaction is the most common unwelcome event related to the use of metal mesh stents in the ureter. We evaluated the effect of zotarolimus eluting stent (ZES- Endeavor Resolute, Medtronics Inc, USA) in porcine and rabbit ureter. Methods: A ZES and a bare metal stent (BMS) were inserted in each ureter of 10 pigs and 6 rabbits. The insertion was performed by retrograde approach. Computerized tomography (CT) was used for the evaluation of porcine ureters while intraoperative intravenous pyelography (IVP) for rabbit ureters. The follow-up included CT or IVP every week for the following 4 weeks for pigs and 8 weeks for rabbits. Renal scintigraphies were performed prior to stent insertion and during the 3rd week in all animals. Optical coherence tomography (OCT) has been used for the evaluation of the luminal and intraluminal condition of the stented ureters. Histopathologic examination of the stented ureters embedded in glycol-methacrylate was performed. Results: Hyperplastic reaction was present in both stent types. BMSs in 7 porcine ureters were completely obstructed while porcine ureters stented with ZES had hyperplastic tissue which did not result in obstruction. Two rabbit ureters stented by BMS were occluded while no ZES was associated with ureteral obstruction. The function of the 7 porcine renal units and the two rabbit units with obstructed stented ureter was compromised. The OCT revealed increased hyperplastic reaction in the ureters stented by BMSs in comparison to ZESs. Although, hyperplastic reaction was present in all cases, pathology examination revealed significantly more hyperplastic reaction in BMSs. Conclusion: ZESs in the pig and rabbit ureter were not related to hyperplastic reaction resulting in stent occlusion. These stents were related to significantly lower hyperplastic reaction in comparison to BMSs while inflammation rates were similar for both stent types.

Objetivo: O Holmium:YAG laser é o método de litotripsia intracorpórea para cálculos urinários mais recentemente introduzido em nosso meio. O objetivo deste estudo é analisar a eficácia e as complicações imediatas do tratamento de pacientes com cálculos ureterais com essa fonte de energia. Casuística e Métodos: Foram tratados 16 pacientes, nove homens e sete mulheres, portadores de cálculos ureterais sintomáticos, maiores ou iguais a 6 mm, ou com evolução superior a 30 dias. A média de idade foi 42 anos (6- 68 anos). Quatro cálculos estavam localizados no ureter superior, seis no ureter médio e seis no ureter inferior. A técnica empregada foi a de vaporização do cálculo com Holmium:YAG laser, através de ureteroscopia. Utilizou-se exclusivamente ureteroscópio semi-rígido de 7 Fr. Resultados: A taxa de sucesso obtida foi de 87,5%, sem diferença estatisticamente significativa em relação ao relatado na literatura. Todos os cálculos foram fragmentados. Os dois insucessos da série ocorreram com cálculos localizados em ureter superior, em que fragmentos foram deslocados para o rim. As complicações observadas foram três perfurações ureterais e dois casos de febre. Conclusão: O Holmium:YAG laser é eficaz no tratamento endoscópico do cálculo ureteral. Medidas destinadas a prevenir a migração retrógrada do cálculo ou de seus fragmentos devem ser tomadas, principalmente no tratamento dos cálculos localizados em ureter superior. A litotripsia com Holmium:YAG laser não é, entretanto, um método isento de complicações, particularmente no que se refere ao tratamento de cálculos impactados de ureter superior. / Objetive: Holmium:YAG laser is the more recently method of intracorporeal lithotripsy of urinary calculi introduced in our area. The purpose of this study is to analyze the technique and to evaluate the immediate results and complications in the treatment of patients with ureteral calculi. Casuistry and Methods: Sixteen patients were treated, nine men and seven women, carrying symptomatic ureteral stones, bigger than 6 mm or with evolution superior to 30 days. The average age was 42 years old (6-88 years old). Four stones were localized in upper ureter, six in middle ureter, and six in lower ureter. The technique employed was the vaporization of the stone with Holmium:YAG laser, through ureteroscopy. It was used exclusively 7-Fr semirigid ureteroscope. Results: The rate of success attained was of 87.5%, with no statistically significant differences regarding the reports in literature. All the stones were fragmented. The two failures of the series occurred with stones localized in upper ureter, in which fragments were displaced to kidney. The complications observed were three ureteral perforations and two fever cases. Conclusion: Holmium:YAG laser is effective in the endoscopic treatment of ureteral stones. Measures aimed at preventing retrograde migration of stones or fragments should be taken, mainly when the stone are located in the upper ureter. However, lithotripsy with Holmium:YAG laser may be associated with complications, particularly in what concerns the treatment of impacted stones.

Purpose To report contemporary epidemiological data and treatment trends for upper tract urothelial carcinoma (UTUC) in Germany over a 14-year period. Methods We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2018/2019. The significance of changes over time was evaluated via regression analysis. Survival outcomes were calculated using the Kaplan–Meier method. Results There was a non-significant increase in the age-standardized incidence rate from 2.5/100,000 in 2006 to 2.9/100.000 in 2018. 13% of patients presented with lymph node metastasis and 7.6% of patients presented with distant metastasis at primary diagnosis. The 5-year overall survival was estimated at 45% and the 10-year overall survival at 32%. Endoscopic biopsies of the renal pelvis and ureter as well as ureteroscopies with excision/destruction of UTUC all increased significantly over the study period. The number of radical nephroureterectomies (RNU) for UTUC steadily increased from 1643 cases in 2006 to 2238 cases in 2019 (p < 0.005) with a shift from open surgery towards minimally invasive surgery. Complex reconstructive procedures like ileal ureter replacement or autotransplantation are rarely performed for urothelial carcinoma of the ureter. Conclusion Diagnostic and therapeutic procedures for UTUC have increased and minimally invasive nephroureterectomy is the predominant approach concerning radical surgery in 2019.

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a 0,89). O NGAL, por sua vez, teve AUC de 0,71 (95% CI 0,61 a 0,83), CA19- 9 teve AUC de 0,70 (95% CI 0,60 a 0,81) e (beta2M) apresentou AUC de 0,61 (95% CI 0,50 a 0,73), sendo o único biomarcador com propriedades inadequadas neste cenário. O KIM-1 foi o marcador mais sensível com o ponto de corte 170,4 pg/mg de creatinina (sensibilidade 91,4%, especificidade 59,1%) e o CA 19-9 o mais específico para o ponto de corte de 51,3 U/mg de creatinina (sensibilidade 48,9%, especificidade 88,0%), enquanto o NGAL foi o que apresentou maior queda após desobstrução, com 90,0% dos pacientes apresentando clareamento superior a 50%. CONCLUSÕES: A avaliação dos biomarcadores urinários é útil no diagnóstico de obstrução em adultos com EJUP submetidos a pieloplastia videolaparoscópica. O KIM-1 foi o marcador mais sensível e o CA 19-9 o mais específico, enquanto o NGAL foi o que apresentou maior que com a desobstrução. Houve queda das concentrações dos marcadores após pieloplastia no período estudado. O papel exato dos biomarcadores urinários no cenário de obstrução em adultos deve ser mais amplamente investigado / INTRODUCTION AND OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is an important cause of urinary tract obstruction and can lead to progressive deterioration of renal function. Thus the development of novel non-invasive methods capable of discriminating obstruction and hydronephrosis may be useful. Elevation of urinary biomarkers may provide early evidence of kidney damage in urinary obstruction. In this scenario, urinary concentrations of KIM-1 may be elevated following proximal tubular injury, while NGAL may increase as result of injury to proximal or distal tubule as well as to loop of Henle, CA19-9 after overproduction in the obstructed tubule and ?2 microglobulin (beta2M) after injury to the glomerulus or the proximal tubule. The aim of this study was to evaluate the diagnostic properties of these urinary biomarkers in adults with UPJO. METHODS: We prospectively studied consecutive patients older than 18 years diagnosed with UPJO undergoing laparoscopic pyeloplasty from December 2013 to February 2015 in our institution. Exclusion criteria included patients with bilateral UPJO, unilateral UPJO with contralateral pathologic kidney, solitary kidney, history of previous surgical treatment for UPJO or glomerular filtration rate below 60 ml/min/1,73m2. Each patient provided four voided urine samples for biomarker measurement, one at preoperative consultation and the others at 1, 3 and 6 months of postoperative follow-up. Healthy individuals with no hydronephrosis on ultrasound evaluation constituted our control group. RESULTS: We included 47 patients with a mean age of 38.6 ± 12.7 years (range 19-64 years), from which 17 (36.2%) were males and 30 (62.8%) were females. The control group consisted of 40 subjects with no statistical difference to the study group regarding age (p = 0.95) and gender (p = 0.82). KIM-1 had an area under the curve (AUC) of 0.79 (95% CI 0.70 to 0.89) and was the biomarker with the best diagnostic properties. CA19-9 had an AUC of 0.70 (95% CI 0.60 to 0.81), NGAL had an AUC of 0.71 (95% CI 0.61 to 0.83) and beta2M had an AUC of 0.61 (95% CI 0.50 to 0.73). KIM-1 was the most sensitive marker with a cutoff of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%) whereas CA 19-9 as the most specific one, displaying a cutoff of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). NGAL showed the greatest decrease in urinary concentrations after pyeloplasty, in which 90.0% of patients had a clearance greater than 50% in comparison to preoperative values. CONCLUSIONS: The evaluation of urinary biomarkers is useful in the assessment of UPJO in adults undergoing laparoscopic pyeloplasty. Urinary concentrations of CA 19-9, NGAL and KIM-1 were elevated in patients with UPJO and significantly decreased after pyeloplasty. The exact role of those biomarkers in the setting of obstruction in adults should be further evaluated

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a 0,89). O NGAL, por sua vez, teve AUC de 0,71 (95% CI 0,61 a 0,83), CA19- 9 teve AUC de 0,70 (95% CI 0,60 a 0,81) e (beta2M) apresentou AUC de 0,61 (95% CI 0,50 a 0,73), sendo o único biomarcador com propriedades inadequadas neste cenário. O KIM-1 foi o marcador mais sensível com o ponto de corte 170,4 pg/mg de creatinina (sensibilidade 91,4%, especificidade 59,1%) e o CA 19-9 o mais específico para o ponto de corte de 51,3 U/mg de creatinina (sensibilidade 48,9%, especificidade 88,0%), enquanto o NGAL foi o que apresentou maior queda após desobstrução, com 90,0% dos pacientes apresentando clareamento superior a 50%. CONCLUSÕES: A avaliação dos biomarcadores urinários é útil no diagnóstico de obstrução em adultos com EJUP submetidos a pieloplastia videolaparoscópica. O KIM-1 foi o marcador mais sensível e o CA 19-9 o mais específico, enquanto o NGAL foi o que apresentou maior que com a desobstrução. Houve queda das concentrações dos marcadores após pieloplastia no período estudado. O papel exato dos biomarcadores urinários no cenário de obstrução em adultos deve ser mais amplamente investigado / INTRODUCTION AND OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is an important cause of urinary tract obstruction and can lead to progressive deterioration of renal function. Thus the development of novel non-invasive methods capable of discriminating obstruction and hydronephrosis may be useful. Elevation of urinary biomarkers may provide early evidence of kidney damage in urinary obstruction. In this scenario, urinary concentrations of KIM-1 may be elevated following proximal tubular injury, while NGAL may increase as result of injury to proximal or distal tubule as well as to loop of Henle, CA19-9 after overproduction in the obstructed tubule and ?2 microglobulin (beta2M) after injury to the glomerulus or the proximal tubule. The aim of this study was to evaluate the diagnostic properties of these urinary biomarkers in adults with UPJO. METHODS: We prospectively studied consecutive patients older than 18 years diagnosed with UPJO undergoing laparoscopic pyeloplasty from December 2013 to February 2015 in our institution. Exclusion criteria included patients with bilateral UPJO, unilateral UPJO with contralateral pathologic kidney, solitary kidney, history of previous surgical treatment for UPJO or glomerular filtration rate below 60 ml/min/1,73m2. Each patient provided four voided urine samples for biomarker measurement, one at preoperative consultation and the others at 1, 3 and 6 months of postoperative follow-up. Healthy individuals with no hydronephrosis on ultrasound evaluation constituted our control group. RESULTS: We included 47 patients with a mean age of 38.6 ± 12.7 years (range 19-64 years), from which 17 (36.2%) were males and 30 (62.8%) were females. The control group consisted of 40 subjects with no statistical difference to the study group regarding age (p = 0.95) and gender (p = 0.82). KIM-1 had an area under the curve (AUC) of 0.79 (95% CI 0.70 to 0.89) and was the biomarker with the best diagnostic properties. CA19-9 had an AUC of 0.70 (95% CI 0.60 to 0.81), NGAL had an AUC of 0.71 (95% CI 0.61 to 0.83) and beta2M had an AUC of 0.61 (95% CI 0.50 to 0.73). KIM-1 was the most sensitive marker with a cutoff of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%) whereas CA 19-9 as the most specific one, displaying a cutoff of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). NGAL showed the greatest decrease in urinary concentrations after pyeloplasty, in which 90.0% of patients had a clearance greater than 50% in comparison to preoperative values. CONCLUSIONS: The evaluation of urinary biomarkers is useful in the assessment of UPJO in adults undergoing laparoscopic pyeloplasty. Urinary concentrations of CA 19-9, NGAL and KIM-1 were elevated in patients with UPJO and significantly decreased after pyeloplasty. The exact role of those biomarkers in the setting of obstruction in adults should be further evaluated

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-18T17:29:53Z No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-22T15:11:02Z (GMT) No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) / Made available in DSpace on 2016-07-22T15:11:02Z (GMT). No. of bitstreams: 1 fabianaaparecidamayrinkdeoliveira.pdf: 602450 bytes, checksum: 44abccc7edd994e7c93876d1aac063dd (MD5) Previous issue date: 2011-02-24 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Justificativa e Objetivo: Independente da etiologia, a doença renal crônica (DRC) envolve fibrose generalizada e progressiva do tecido, atrofia tubular e a perda da função renal. Atualmente, as terapias eficazes para esta condição são escassas. Neste estudo, foram investigados os efeitos da terapia laser de baixa intensidade (LLLT) sobre a fibrose intersticial, que ocorre após obstrução ureteral unilateral (OUU) em ratos, um modelo experimental de doença renal crônica. Materiais e Métodos: Foram utilizados 32 ratos Wistar, 8 em cada grupo, machos, com 250 a 300g de peso aproximadamente e 8 semanas de idade. O rim obstruído de metade dos ratos, submetidos à OUU receberam dose única intra-operatória do LLLT (AlGaAs laser, 780 nm, 22,5 J / cm ², 30 mW, 30 segundos em cada um dos nove pontos). Após 14 dias, a fibrose renal foi avaliada pela coloração por picrosírius e medição da área transversal sob luz polarizada. Análise imunohistoquímica quantificou células do tecido renal que expressam marcadores de fibroblastos (FSP-1) e miofibroblastos (α-SMA). RT-PCR foi realizado para determinar a expressão de mRNA de genes chaves relacionados com a fibrose: TGF-β1, Smad3 e colágeno I (Col I). Resultados: No grupo OUU e tratado pelo LLLT os animais apresentaram menos fibrose renal do que os animais obstruídos (OUU). α-SMA, TGF-β1 e Smad3 foram aumentados no interstício renal de ratos OUU. LLLT reduziu a expressão de todas essas moléculas. LLLT não parece ter um efeito significativo no Col I ou FSP-1, que também foram induzidos por OUU. Conclusão: Pela primeira vez, nós mostramos que LLLT tem um efeito protetor em relação à fibrose intersticial renal. Entende-se que, atenuando a inflamação, a laserterapia pode impedir a ativação tubular e transdiferenciação, que são os dois processos principais que formam a fibrose renal no modelo OUU. / Background and Objective: Regardless of the etiology, chronic kidney disease (CKD) involves progressive widespread tissue fibrosis, tubular atrophy and loss of kidney function. At present, effective therapies to this condition are lacking. We investigated the effects of low level laser therapy (LLLT) on the interstitial fibrosis that occurs after unilateral ureteral obstruction (UUO) in rats, an experimental model of CKD. Study Design/Materials and Methods: We used 32 Wistar rats, 8 in each group, males, 250 to 300g weight and 8 weeks old. The occluded kidney of half of the Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm², 30 mW, 30 seconds on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining and measurement of the cross-sectional area under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. RT-PCR was performed to determine the mRNA expression of key fibrosis-related genes, namely TGF-β1, Smad3 and collagen I (Col I). Results: The UUO-LLLT animals had less severe renal fibrosis than OUU animals. α- SMA, TGF-β1 and Smad3 were increased in the renal interstitium of UUO rats. LLLT reduced the expression of all of these molecules. LLLT did not appear to have a significant effect on Col I or FSP-1, which were also induced by UUO. Conclusion: For the first time, we showed LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

This thesis addresses the three principal questions concerning the development of CT urography for investigating haematuria and each question is the subject of a separate chapter. The questions are: What is the reasoning behind using CT urography? What is the optimum diagnostic strategy using CT urography? What are the problems with using CT urography and how may solutions be provided? Haematuria can signify serious disease such as urinary tract stones, renal cell cancer, upper tract urothelial cancer (UTUC) and bladder cancer (BCa). CT urography is defined as contrast enhanced CT examination of kidneys, ureters and bladder. The technique used here includes unenhanced, nephrographic and excretory-phases for optimized diagnosis of stones, renal masses and urothelial cancer respectively. The reasoning behind using excretory-phase CT urography for investigating haematuria is based on results showing its high diagnostic accuracy for UTUC and BCa. Patients with haematuria are classified as low risk or high risk for UTUC and BCa, by a risk score, determined by the presence/absence of risk factors: age > 50 years, visible or nonvisible haematuria, history of smoking and occupational exposure. The optimum diagnostic strategy for patients at high risk for urothelial cancer, uses CT urography as a replacement test for ultrasonography and intravenous urography and as a triage test for flexible and rigid cystoscopy, resulting in earlier diagnosis and potentially improving prognosis. For patients at low risk, ultrasonography, unenhanced and nephrographic-phase CT urography are proposed as initial imaging tests. Problems with using CT urography include false positive results for UTUC, which are eliminated by retrograde ureteropyelography-guided biopsy, an innovative technique, for histopathological confirmation of diagnosis. Recommendations for the NHS and possible future developments are discussed. CT urography, including excretory-phase imaging, is recommended as the initial diagnostic imaging test before cystoscopy for patients with haematuria at high risk for urothelial cancer.