Renal anastomosing haemangioma.

Anastomosing haemangioma is a rare subtype of haemangioma, a benign vascular tumour. Its rarity stems from its low incidence and difficulty in obtaining an accurate diagnosis. In addition, its histological resemblance to malignant neoplasms may lead to unnecessary overtreatment. Here, we report the case of an asymptomatic male patient with a slight increase in kidney function who underwent an abdominal ultrasound and a CT scan for suspected renal cell carcinoma. Subsequently, the patient underwent laparoscopic left radical nephrectomy. Histological analysis revealed an anastomosing haemangioma. The patient is currently asymptomatic with no relapse or imaging progression. We also present a literature review on anastomosing haemangioma.

Laparoscopic treatment of entero-neobladder fistula after radical cystectomy.

Entero-neovesical fistula is a rare complication of orthotopic ileal neobladder after radical cystectomy occurring in <2% of cases. Surgical treatment is usually required and includes open resection of the affected bowel tract and reconstitution of bowel transit. Here we present a case of a laparoscopic treatment of entero-to-neobladder fistula 8 years after laparoscopic radical cystectomy to demonstrate the feasibility and safety of minimally invasive treatment (Supplementary Video). To the best of our knowledge, this is the first report of minimally invasive treatment of entero-neobladder fistula.

Do all patients with suspicious prostate cancer need Multiparametric Magnetic Resonance Imaging before prostate biopsy?

OBJECTIVES: Multiparametric magnetic resonance imaging (mpMRI) is a useful tool to diagnose prostate cancer (PCa) but its cost is not negligible. In order to reduce costs and minimize time to diagnosis, it is necessary to establish which patients benefit the most from doing mpMRI prior to prostate biopsy (PB). Our aim was to test if mpMRI still predicts PCa and clinically significant PCa (csPCa) in patients with high clinical suspicion of cancer, defined as prostate specific antigen (PSA) > 10 ng/ml, PSA-Density (PSAD) > 0.15 ng/ml/cc or suspicious digital rectal examination (DRE). MATERIALS AND METHODS: We retrospectively collected data on 206 patients who underwent mpMRI before PB at our Department from January 2017 to July 2018. mpMRI results were classified using Prostate Imaging Reporting and Data System (PI-RADS) version 2. In primary analysis, we evaluated the association of mpMRI with PCa and csPCa and stratified this model for low and high clinical suspicion of cancer. In secondary analysis, we determined the rate of negative PB results in patients with high suspicion of cancer and compared theses rates with those obtained if only those with PI-RADS 3-5 would be biopsied. RESULTS: In primary analysis and overall, mpMRI was predictive of PCa and csPCa. In stratified analysis, mpMRI was still significantly associated with csPCa in patients with PSA > 10 ng/ml and PSAD > 0.15 ng/ml/cc, but not in those with suspicious DRE. In secondary analysis, negative result rates were lower if only patients with PI-RADS 3-5 were biopsied, even in subgroups with high suspicion of cancer based on PSA and PSAD. In patients with suspicious DRE, however, the rate of negative results did not change significantly if only patients with PI-RADS 3-5 were biopsied. CONCLUSIONS: mpMRI is still useful in predicting csPCa in patients with PSA > 10 ng/mL and PSAD > 0.15 ng/ml/cc. If DRE is suspicious, though, mpMRI might be no longer useful in the prediction of PCa.

Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism.

Benign prostate hyperplasia is a dysfunctional disease with an elevated prevalence. Despite the accepted impact of aging and testosterone (TES) in its pathophysiology, its aetiology remains unknown. Recent studies described that serotonin (5-HT) inhibits benign prostate growth through the modulation of the androgen receptor, in the presence of TES. Accordingly, this work aimed to determine the impact of castration and TES replacement in plasmatic and prostatic 5-HT regulation. C57BL/6 mice were submitted to surgical castration and divided into three groups, continually exposed to either vehicle or different TES doses for 14 days. Plasmatic 5-HT concentration was measured before and after castration, and after TES reintroduction. Finally, total prostatic weight and intra-prostatic 5-HT were determined in the different groups. Our results demonstrate that mice prostate exhibits high 5-HT tissue levels and that intra-prostatic total 5-HT was independent of castration or TES reintroduction, in all studied groups. Also, 5-HT plasmatic concentration significantly increased after castration and then normalized after TES administration. Our findings revealed that mice prostate has a high 5-HT content and that total prostatic 5-HT levels do not depend on androgens' action. On the other hand, castration induced a significant increase in plasmatic 5-HT concentration, raising the hypothesis that androgens might be regulating the production of extra-prostatic 5-HT.

Is Repeat Transurethral Resection Always Needed in High-Grade T1 Bladder Cancer?

Re-staging transurethral resection, the so-called repeat TUR (Re-TUR), is mandatory in case of incomplete first transurethral resection of bladder tumor (TURBT). In completely resected high grade T1 tumors, Re-TUR is recommended but question remains whether it provides advantages in terms of recurrence-free survival (RFS), progression-free survival (PFS), and cancer specific survival (CSS). The present study aimed to determine whether Re-TUR improves such outcomes in patients with completely resected high-grade T1 bladder cancer (BC). We queried our prospectively maintained database to identify patients with completely resected high-grade T1 BC who underwent (Group A) or not (Group B) Re-TUR before starting intravesical instillations of Bacillus Calmette-Guerin (BCG). The impact of Re-TUR as well as of other tested variables on RFS, PFS, and CSS was tested by Kaplan-Meier method and Log-rank testing. A total of 118 patients underwent Re-TUR, which pointed out no BC in 61 (51.7%), NMIBC in 54 (45.8%) and pT2 disease in 3 (2.5%). The 3 patients with pT2 disease underwent cystectomy, whereas all others were offered BCG treatment. Forty-two patients refused BCG treatment while 2 did not complete it; therefore, Group A (Re-TUR before BCG treatment) consisted of 71 patients whereas Group B consisted of 40 patients who refused Re-TUR but completed BCG treatment. Mean follow-up was 60 months (range 12-142). Kaplan-Meier curves and Log-rank testing showed no difference in RFS, PFS and CSS between patients who had (Group A) or had not (Group B) Re-TUR before starting BCG treatment. Our findings suggest that a Re-TUR in patients with a completely resected high-grade T1 BC does not translate into a better oncological outcome. Given its impact on both patients and healthcare system, the need for Re-TUR in completely resected high grade T1 BC should be further investigated into the framework of a randomized study.

Percutaneous nephrostomy vs ureteral stent for hydronephrosis secondary to ureteric calculi: impact on spontaneous stone passage and health-related quality of life-a prospective study.

Ureteral calculi can be associated with urinary drainage blockage, requiring urinary diversion with percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). Currently no evidence exists to support the superiority of one method over the other. This study proposes to compare both approaches regarding the probability of spontaneous stone passage (SSP) and its effect on patient's quality of life (QoL). A prospective trial was carried out from July to October of 2017. 50 patients were selected with hydronephrosis secondary to ureteral stones requiring urgent urinary diversion and divided into two groups according to diversion technique: percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). The rate of SSP and QoL were evaluated. A PCN group (18 patients) and a RUS group (32 patients) were set. Stone size was higher in PCN (median 92 mm2) than RUS (median 47 mm2) (p = .012). The rate of SSP was 25% in RUS group and 38.9% in PCN. On the univariable analysis no statistical effect was found; however, when adjusted for stone size, location, previous ureteral manipulation and expulsive therapy, PCN showed a significant higher chance of SSP than RUS (OR = 6667). Besides, it was found that 30.2% (n = 13) of stones had an upward displacement associated with retrograde endoscopy. A significant decrease between pre- and post-intervention QoL was found with RUS (p < .001), but not found with PCN (p = .206). Patients in RUS group experienced more urinary symptoms, mostly haematuria (68.7% vs 16.7% in PCN group < .001) and dysuria (78.3% vs 16.7% in PCN group, p < .001). PCN was associated with a higher rate of spontaneous stone passage when adjusted for stone size and location. Moreover, PCN was better tolerated and associated with fewer urinary symptoms when compared with RUS.

Late presentation of vesicoureteral reflux: An unusual cause of pyelonephritis in adults.

INTRODUCTION: Vesicoureteral reflux (VUR) corresponds to the reflux of urine from the bladder into the upper urinary system. It can be a congenital or an acquired anomaly and although its incidence is high in children it is uncommon in the adult life. One of its presentations in the adult population is the presence of recurrent Pyelonephritis. CASE PRESENTATION: Here we report a case of an adult patient with repetitive uncomplicated pyelonephritis caused by VUR. VUR was successfully managed endoscopically with subureteral injection of a bulking agent. A literature review of adult presenting VUR was performed. DISCUSSION: The first presentation of VUR in the adult life is rare. One of the most typical presentation is the presence of recurrent uncomplicated Pyelonephritis. Although no guidelines exists to study the presence of VUR in adult patients with Pyelonephritis, in the presence of several recurrent episodes of Pyelonephritis we should think in VUR as a possible cause. Even in adults, endoscopic management of VUR is an effective treatment with low morbidity. CONCLUSION: VUR can first present in the adult life, with recurrent episodes of UTI. The diagnosis is a suspicious one and is confirmed by VUCG. VUR in adults can be effectively managed with endoscopic injection of bulking agents.

Resistance of different guidewires to laser injury: an in-vitro experiment.

BACKGROUND: In urology, lasers are used in a variety of endoscopic procedures such as ureteroscopy and retrograde renal surgery for stone fragmentation of urinary calculi and ablation of urothelial tumors. To perform these procedures, guidewires are used as a preliminary safe-mainstay for referencing the urinary tract. This study aims to determine the effect of two different lasers: holmium:YAG (Ho:YAG) and thulium:YAG (Tm:YAG) lasers on metal guidewires with PTFE coating (PTFE), nitinol guidewires with hydrophilic coating (Hydrophilic) and nitinol guidewires with hydrophilic listed coating (Zebra). METHODS: Different combinations of frequency (5, 10 and 12 Hz) and energy per pulse (0.5, 1.5, and 2.6 J) of Ho:YAG laser were applied on the three kinds of guidewires in two experiments (50 J vs. 100 J of total energy). For the Tm:YAG laser three power levels (5, 35, and 70 W) with a total energy of 100 J were applied to the guidewires. The degree of damage (0 to 5) of the guidewire was assessed after each laser application. RESULTS: A higher degree of injury of guidewires was related to higher values of total energy used for the Ho:YAG laser (P=0.036), and to higher values of power applied with the Tm:YAG (P=0.051). The most resistant guidewire to Ho:YAG laser energy was Zebra, followed by PTFE and Hydrophilic (P<0.001). With the Tm:YAG laser, PTFE guidewire appears to be the most resistant and the Hydrophilic the most fragile, although without reaching the statistical significance (P=0.223). CONCLUSIONS: Both lasers revealed a harmful effect on the three tested guidewires. There was an association between the degree of injury and the amount of Ho:YAG laser energy and Tm:YAG laser power. The guidewire Zebra proved to be the safest when using Ho:YAG laser and the PTFE guidewire the most resistant to laser Tm:YAG. Further studies are necessary to confirm these results.

[Smoking Cessation after Bladder Cancer Diagnosis]. / Cessação Tabágica após o Diagnóstico de Cancro da Bexiga.

INTRODUCTION: Smoking is an important risk factor for the development, recurrence and progression of bladder cancer. Our aim was to analyze smoking habits after diagnosis in bladder cancer patients. Additionally, we evaluated patient knowledge about smoking as a risk factor and the urologist role in promoting abstinence. MATERIAL AND METHODS: A cross-sectional, observational and descriptive study was performed in bladder cancer patients, diagnosed between January 2013 and September 2015 (n = 160) in Braga Hospital, in Portugal. RESULTS: Smoking history was present in 71.9% of the sample, with 21.9% current smokers, (40.7% of abstinence after diagnosis). Smoking was acknowledged as a risk factor by 74.4% of the sample, with only 51.3% of ever smokers and 24.4% of non-smokers recognizing smoking as the leading risk factor (p = 0.008). The presence of other household smokers were significantly higher in patients who continued smoking (40%) than in ex-smokers after diagnosis (4.2%) (p = 0.005). The majority of smokers at diagnosis (83.1%) were advised to quit by their urologist, but only one smoker (1.7%) was offered any specific intervention to aid in cessation. DISCUSSION: Smoking is not recognized as the leading risk factor for bladder cancer. This limited awareness, associated with the known difficulties in quitting smoking and the observed lack of smoking cessation interventions, may account for the high current smoking prevalence, albeit in line with other studies. CONCLUSION: This study highlights the need for efficient smoking cessation programs directed to bladder cancer patients.

Introdução: O tabagismo é um importante fator de risco para o desenvolvimento, recorrência e progressão do cancro da bexiga. Este estudo pretendia analisar os hábitos tabágicos após o diagnóstico em doentes com cancro da bexiga. Adicionalmente, foi avaliado o reconhecimento do tabagismo como fator de risco e a atuação médica na promoção da cessação tabágica. Material e Métodos: Estudo transversal, observacional e descritivo realizado em doentes com cancro da bexiga, diagnosticados entre janeiro de 2013 e setembro de 2015 (n = 160) no Hospital de Braga. Resultados: História tabágica estava presente em 71,9% da amostra, com 21,9% de tabagismo atual (40,7% de abstinência após o diagnóstico). O tabagismo foi reconhecido como fator de risco por 74,4% dos doentes, mas apenas 51,3% dos doentes com história tabágica e 24,4% dos não fumadores referem o tabagismo como a principal causa etiológica (p = 0,008). A presença de outros fumadores em casa foi significativamente maior em doentes que mantiveram tabagismo (40%) do que em ex-fumadores após o diagnóstico (4,2%) (p = 0,005). A maioria dos fumadores (83,1%) refere ter sido aconselhada a deixar de fumar, mas apenas um (1,7%) recebeu apoio específico para a cessação. Discussão: O tabagismo não é adequadamente reconhecido como a principal etiologia de cancro da bexiga. Este desconhecimento, aliado à reconhecida dificuldade na abstinência tabágica e ao défice de estratégias promotoras de cessação tabágica observados, poderá justificar a elevada prevalência de fumadores atuais, todavia, em linha com outros estudos. Conclusão: Este estudo evidencia a necessidade de programas de cessação tabágica eficientes dirigidos a pacientes com cancro da bexiga.

Video-Based Surgical Learning: Improving Trainee Education and Preparation for Surgery.

BACKGROUND: Since the end of the XIX century, teaching of surgery has remained practically unaltered until now. With the dawn of video-assisted laparoscopy, surgery has faced new technical and learning challenges. Due to technological advances, from Internet access to portable electronic devices, the use of online resources is part of the educational armamentarium. In this respect, videos have already proven to be effective and useful, however the best way to benefit from these tools is still not clearly defined. AIMS: To assess the importance of video-based learning, using an electronic questionnaire applied to residents and specialists of different surgical fields. METHODS: Importance of video-based learning was assessed in a sample of 141 subjects, using a questionnaire distributed by a GoogleDoc online form. RESULTS: We found that 98.6% of the respondents have already used videos to prepare for surgery. When comparing video sources by formation status, residents were found to use Youtube significantly more often than specialists (p < 0.001). Additionally, residents placed more value on didactic illustrations and procedure narration than specialists (p < 0.001). On the other hand, specialists prized surgeon's technical skill and the presence of tips and tricks much more than residents (p < 0.001). CONCLUSION: Video-based learning is currently a hallmark of surgical preparation among residents and specialists working in Portugal. Based on these findings we believe that the creation of quality and scientifically accurate videos, and subsequent compilation in available video-libraries appears to be the future landscape for video-based learning.

Serotonin regulates prostate growth through androgen receptor modulation.

Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT's inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT's inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.

The role of ephrins-B1 and -B2 during fetal rat lung development.

UNLABELLED: BACKGROUND/ AIMS: The knowledge of the molecular network that governs fetal lung branching is an essential step towards the discovery of novel therapeutic targets against pulmonary pathologies. Lung consists of two highly branched systems: airways and vasculature. Ephrins and its receptors, Eph, have been implicated in cardiovascular development, angiogenesis and vascular remodeling. This study aims to clarify the role of these factors during lung morphogenesis. METHODS: Ephrins-B1, -B2 and receptor EphB4 expression pattern was assessed in fetal rat lungs between 15.5 and 21.5 days post-conception, by immunohistochemistry. Fetal rat lungs were harvested at 13.5 dpc, cultured during 4 days and treated with increasing doses of ephrins-B1 and -B2 and the activity of key signaling pathways was assessed. RESULTS: Ephrin-B1 presents mesenchymal expression, whereas ephrin-B2 and its receptor EphB4 were expressed by the epithelium. Both ephrins stimulated pulmonary branching. Moreover, while ephrin-B1 did not affect the pathways studied, ephrin-B2 supplementation decreased activity of JNK, ERK and STAT. This study characterizes the expression pattern of ephrins-B1, -B2 and EphB4 receptor throughout rat lung development. CONCLUSION: Our data highlight a possible role of ephrins as molecular stimulators of lung morphogenesis. Moreover, it supports the idea that classical vascular factors might play a role as airway growth promoters.

Three-dimensional vs standard laparoscopy: comparative assessment using a validated program for laparoscopic urologic skills.

OBJECTIVE: To compare the last generation of 3-dimensional imaging (3D) vs standard 2-dimensional imaging (2D) laparoscopy. MATERIALS AND METHODS: A prospective observational study was conducted during the 4th Minimally Invasive Urological Surgical Week Course held in Braga (Portugal) in April 2013. The course participants and faculty were asked to perform standardized tasks in the dry laboratory setting and randomly assigned into 2 study groups; one starting with 3D, the other with 2D laparoscopy. The 5 tasks of the European Training in Basic Laparoscopic Urological Skills were performed. Time to complete each task and errors made were recorded and analyzed. An end-of-study questionnaire was filled by the participants. RESULTS: Ten laparoscopic experts and 23 laparoscopy-naïve residents were included. Overall, a significantly better performance was obtained using 3D in terms of time (1115 seconds, interquartile range [IQR] 596-1469 vs 1299 seconds, IQR 620-1723; P = .027) and number of errors (2, IQR 1-3 vs 3, IQR 2-5.5; P = .001). However, the experts were faster only in the "peg transfer" task when using the 3D, whereas naïves improved their performance in 3 of the 5 tasks. A linear correlation between level of experience and performance was found. Three-dimensional imaging was perceived as "easier" by a third of the laparoscopy-naïve participants (P = .027). CONCLUSION: Three-dimensional imaging seems to facilitate surgical performance of urologic surgeons without laparoscopic background in the dry laboratory setting. The advantage provided by 3D for those with previous laparoscopic experience remains to be demonstrated. Further studies are needed to determine the actual advantage of 3D over standard 2D laparoscopy in the clinical setting.

The role of glycoprotein 130 family of cytokines in fetal rat lung development.

The glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching.

Leukemia inhibitory factor in rat fetal lung development: expression and functional studies.

BACKGROUND: Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. METHODOLOGY/PRINCIPAL FINDINGS: LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. CONCLUSIONS/SIGNIFICANCE: The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.

Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia.

Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH.