Transvesical route for NOTES urological applications: advances & controversies

Natural Orifice Transluminal Endoscopic Surgery (NOTES) has emerged recently in the experimental surgical field, innovating for the passage of luminal barrier, the absence of scars and reduction of post-operative pain. Among the various ports of access (transvaginal, transgastric, transvesical and transcolonic), this paper is an update on advances & controversies of transvesical port for NOTES Urological applications

New endoscopic procedure for bladder wall closure: results from the porcine model

Upper urinary tract urothelial carcinomas are usually managed by radical nephroureterectomy (RNU), often followed by intravesical chemotherapy to minimize recurrence. Open surgery is the gold standard procedure for RNU, but it associates with high morbidity, and it has been increasingly replaced by minimally invasive strategies, such as laparoscopy and endoscopy. Although effective, endoscopic ureteral excision leaves the bladder unsutured, increasing the risk of tumor spillage, and precluding the immediate administration of intravesical chemotherapy. Here we describe a new method to close the bladder wall after ureteral excision, using barbed sutures via the endoscopic access. Our results in 8 female pigs demonstrate that this method is effective to close the bladder wall. The procedure was completed in a median time of 24 min, and no adverse events were registered in the follow-up or at the three-week necropsy. This technique improves a previous approach described by our group because the device is more flexible and allows to tie the knots inside the bladder. Barbed sutures have been used in the clinical practice for other types of surgeries, and therefore this method can further be adapted to human patients with no safety concerns. Its use may allow to administer intravesical chemotherapy, which reduces tumor recurrence and improves patient outcomes.The authors acknowledge Ana Goios for support in manuscript writing and technical editing, and for producing original illustrations for Figure 3. Doctoral grant of CUF Jose de Mello Saude

Tailor made degradable ureteral stents from natural origin polysaccharides

A urinary stent is defined as a thin tube, which is inserted in the ureter to prevent or treat the obstruction of urine flow from the kidney. Silicone, latex, polyvinylchloride and polyurethanes are the most widely used materials for the preparation of stents. Nonetheless, severe clinical complications may result from the use of these materials such as fracture, encrustation and infection. In some of the cases, the ureteral stents are temporary and it is often required a second surgery to remove the stent. The main complications with ureteral stents are dislocation, infection, and blockage by encrustation [1]. Recently, a tendency has been noticed favouring less invasive approaches (e.g. pharmacological or catheterization) in treating patients who exhibit symptoms or signs of urinary retention [2]. Currently, nearly 100% of the people who have an urological stent are likely to develop a bacterial infection within 30 days, which increases morbidity threefold [1]. Different types of temporary and permanent stents have been introduced into urological practice to relieve obstructions [3]. Particular attention should be devoted to polymers as they represent a highly versatile class of materials. Despite the fact that silicon continues to be the gold standard material for urological stents, there have been fast developments in manufacturing processes, as well as the introduction of new biodegradable materials in order to overcome the drawbacks of the available products. Polyurethane continues to be the most widely used material for polymeric stents; however it frequently promotes biofilm formation and bacterial adhesion leading to severe infections [2]. The concerns regarding existing stents are the motivation to design new biodegradable urological stent systems based on natural polymers, specifically polysaccharides, which present inherent biocompatibility, anti-bacterial properties and that can be tailor-made into a custom suitable stent for a particular patient

Presence and severity of lower urinary tract symptoms are inversely correlated with the risk of prostate cancer on prostate biopsy

BACKGROUND: The assessment of lower urinary tract symptoms (LUTS) is common part of urological investigation. Furthermore, patients bother of prostate cancer (PCa) when they are affected of LUTS. This study was aimed to determine whether the presence and severity of LUTS, as assessed by the International Prostate Symptoms Score (IPSS), could help to identify patients at higher risk of prostate cancer (PCa) on prostate biopsy (PBx). In this effort, an initial PCa predictive model was calculated and IPSS was subsequently added. The diagnostic accuracy of both models was compared. METHODS: The analysis of prospectively collected data of patients scheduled for PBx at four academic hospitals between January 2012 and June 2015 was performed. Univariate and multivariate analysis assessed the correlation between the IPSS and the risk of being diagnosed with PCa; Receiver operator characteristic curve (ROC) analysis evaluated the predictive models including or not the IPSS. RESULTS: Of the 1366 enrolled patients, 706 (52%) were diagnosed with PCa. Patients with PCa had a significantly lower IPSS (10.6 +/- 7.4 vs. 12.7 +/- 8.1) than those with benign diagnosis. Multivariate logistic regression analysis showed that age, prostate-specific antigen (PSA), prostate volume and IPSS were the most significant predictors of PBx outcome, (OR 1.61, P=0.001; OR 1.20, P=0.001; OR 0.97, P=0.001; OR 0.74, P=0.004; respectively). ROC curve analysis showed that the addition of IPSS to the predictive model based on age, PSA, DRE and prostate volume significantly improved the model diagnostic accuracy (AUC: 0.776 vs. 0.652; P=0.001). CONCLUSIONS: Presence and severity of LUTS are inversely correlated with the risk of being diagnosed with PCa at PBx. Incorporating the IPSS into predictive models may reduce the risk of unnecessary PBxs.info:eu-repo/semantics/publishedVersio

Biodegradable drug-eluting stents: Targeting urothelial tumors of upper urinary tract

INTRODUCTION & OBJECTIVES: Urothelial tumors of upper urinary tract are ranked among the most common types of cancers worldwide. The current standard therapy to prevent recurrence is intravesical Bacillus Calmetteâ Guerin (BCG) immunotherapy, but it presents several disadvantages such as BCG failure and intolerance. Another way is to use chemotherapy, which is generally better tolerated that BCG. In this case, drugs such as epirubicin, doxorubicin, paclitaxel and gemcitabine are used. Nevertheless, intravesical chemotherapy only prevents recurrence in the short-term. These failings can be partially attributed to the short residence time and low bioavailability of the drug within the upper urinary tract and the cancer cells, resulting in a need for frequent drug instillation. To avoid these problems, biodegradable ureteral stents impregnated by supercritical fluid CO2 (SCF) with each of the four anti-cancer drugs were produced. MATERIAL & METHODS: Four formulations with different concentrations of gelatin and alginate and crosslink agent were tested and bismuth was added to confer radiopaque properties to the stent. The preliminary in vivo validation studies in female domestic pigs was conducted at the University of Minho, Braga, after formal approval by the institutionâ s review board and in accordance with its internal ethical protocol for animal experiments. Paclitaxel, epirubicin, doxorubicin and gemcitabine were impregnated in the stents and the release kinetics was measured in artificial urine solution (AUS) for 9 days by UV spectroscopy in a microplate reader. The anti-tumoral effect of the developed stents in transitional cell carcinoma (TCC) and HUVEC primary cells, used as control, was evaluated. RESULTS: The in vivo validation of this second-generation of ureteral stents performed was herein demonstrated. Biodegradable ureteral stents were placed in the ureters of a female pigs, following the normal surgical procedure. The animals remained asymptomatic, with normal urine flow. The in vitro release study in AUS of the stent impregnated showed a higher release in the first 72h for the four anti-cancer drugs impregnated after this time the plateau was achieved and the stent degraded after 9 days. The direct and indirect contact of the anti-cancer biodegradable stents with the TCC and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the TCC cell line after 72h and no killing effect in the HUVEC cells. CONCLUSIONS: The use of biodegradable ureteral stent in urology clinical practice not only reduce the stent-related symptoms but also open new treatment therapyâ s, like in urothelial tumors of upper urinary tract. Furthermore, we have demonstrated the clinical validation in vivo pig model. This study has thus shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the TCC cell line, with no toxicity observed in the control, non-cancerous cells.The direct and indirect contact of the anti-cancer biodegradable stents with the TCC and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the TCC cell line after 72h and no killing effect in the HUVEC cells. This study has thus shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the TCC cell line, with no toxicity observed in the control, non-cancerous cells

Targeting urothelial tumors of upper urinary tract with drug-eluting stents impregnated by supercritical fluids

Urothelial tumors of upper urinary tract are ranked among the most common types of cancers worldwide and it has been considered as one of the more expensive to treat due of its long-term propensity of recurrence. The current standard therapy to prevent recurrence is intravesical Bacillus Calmette–Guerin (BCG) immunotherapy, but it presents several disadvantages such as BCG failure and intolerance. Another way is to use chemotherapy, that has been reported to be generally better tolerated that BCG. In this case, drugs such as epirubicin, doxorubicin, paclitaxel and gemcitabine are used. Nevertheless, intravesical chemotherapy only prevents recurrence in the short-term[1], [2]. These failings can be partially attributed to the short residence time and low penetration of the drug within the upper urinary tract and the cancer cells, resulting in a need for frequent drug instillation [3]. To avoid these problems, biodegradable ureteral stents impregnated by supercritical fluid CO2 (SCF) with each of the four anti-cancer drugs were produced (figure 1). Four types of drug-eluting biodegradable stents were studied, impregnated with paclitaxel, epirubicin, doxorubicin and gemcitabine. The release kinetics of the impregnated drugs from the anti-cancer drug-eluting stents was measured in artificial urine solution (AUS) for 9 days. The in vitro drugs release from the impregnated biodegradable ureteral stents was analyzed using a microplate reader. The in vitro release study in AUS showed a higher release in the first 72h for the four anti-cancer drugs impregnated after this time the plateau was achieved and the stent degrades after 9 days. Regarding the amount of impregnated drugs by SCF the gemcitabine showed higher amount (109 μg) and the lower amount was obtained for paclitaxel (67 ng). The diffusion coefficient and the impregnation yield were calculated. The anti-tumoral effect of the developed stents in transitional cell carcinoma (TCC) - T24 cell lines was evaluated. T24 cell line was exposed to graded concentrations (0.01 to 2000 ng/ml) of the four drugs for both 4 and 72 hours to determine the sensitivities to each drug (IC50). Toxicity as a result of both direct and indirect contact of the cell lines with the different material conditions of biodegradable stent were studied. The four anti-cancer drugs showed a concentrationdependent inhibitory effect on the T24 and HUVEC cell lines with IC50’s for paclitaxel of 7.30ng and 501.50ng, respectively. The T24 cell line shows to be more sensitive than HUVEC cell line for all the anti-cancer drugs tested. The direct and indirect contact of the anti-cancer biodegradable stents with the T24 and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the T24 cell line after 72h and no killing effect in the HUVEC cells. Finally, this study has shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the T24 cell lines, with no toxicity observed in the control, non-cancerous cells.Luso­- American Foundation's Grant for Internships in the University of California, Berkeley, 2015/CON5/CAN8; FCT PhD Grant (SFRH/BD/97203/2013); European Union's Seventh Framework Programme (FP7/2007­2013) under grant agreement n° REGPOT­CT2012­316331­ POLARIS; Project “Novel smart and biomimetic materials for innovative regenerative medicine approaches (Ref.: RL1 ­ ABMR ­ NORTE­01­0124­FEDER­000016)” cofinanced by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF

Low-cost reusable instrumentation for laparoendoscopic single-site nephrectomy : assessment in a porcine model

Purpose: To test different sets of prebent instruments and a new reusable access device for laparoendoscopic single-site (LESS) surgery. Materials and Methods: Three surgeons with previous experience in LESS performed 12 nephrectomies in six pigs. In all procedures, a multichannel access device (X-CONE_) and a 5-mm extra-long telescope were used. Four sets of prebent instruments with different profiles (S-portal_) were tested: Standard (one straight scissorsand one curved grasper), Cuschieri, Carus, and Leroy set (each of them consisting of two curved instruments with different configurations). Assessment was performed based on both objective (procedure time; time to manage the pedicle; time to free kidney) and subjective parameters (entry=exit of instruments; triangulation; dissection up=down; dissection lateral; retraction; interdependence). The subjective assessment tool used was a Likert type scale (1¼easy to 5¼prohibitive). The access device was assessed by using objective (time to completeinsertion of device after skin incision) and subjective (significant air leakage, movement constraint) parameters. Results: Time to insertion of the X-CONE was <1 minute in all the cases. Surgeons reported significant insufflant leakage in 58% of cases. The procedure was completed in 10=12 (83%) cases. Mean operative time was 8.3_4.2 minutes, being lower for the Carus group (4.5 min) and higher for the standard group (13 min). Among thedifferent sets, the standard one obtained the best mean scores for all subjective parameters. Conclusions: X-CONE allows easy abdominal access, and its reusable properties represent cost savings for LESS compared with disposable devices. Prebent instruments might also represent attractive low-cost tools for LESS

Cessação Tabágica após o Diagnóstico de Cancro da Bexiga

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.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.info:eu-repo/semantics/publishedVersio

A dual-modal CT/US kidney phantom model for image-guided percutaneous renal access

Percutaneous renal access (PRA) is a crucial step in some minimally invasive kidney interventions. During this step, the surgeon inserts a needle through the skin until the kidney target site using fluoroscopy and ultrasound imaging. Recently, new concepts of enhanced image-guided interventions have been introduced in these interventions. However, their validation remains a challenging task. Phantom models have been presented to solve such challenge, using realistic anatomies in a controlled environment. In this work, we evaluate the accuracy of a porcine kidney phantom for validation of novel dual-modal computed tomography (CT)/ultrasound (US) image-guided strategies for PRA. A porcine kidney was combined with a tissue mimicking material (TMM) and implanted fiducial markers (FM). While the TMM mimics the surrounding tissues, the FM are used to accurately assess the registration errors between the US and CT images, providing a valid ground-truth. US and CT image acquisitions of the phantom model were performed and the FM were manually selected on both images. A rigid alignment was performed between the selected FM, presenting a root-mean-square error of 1.1 mm. Moreover, the kidney was manually segmented, presenting volumes of 203 ml and 238 ml for CT and US, respectively. The initial results are promising on achieving a realistic kidney phantom model to develop new strategies for PRA, but further work to improve the manufacturing process and to introduce motion and anatomical artifacts in the phantom is still required.This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project NORTE-01-0145-FEDER-000013, supported by the NORTE 2020, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). J. Gomes-Fonseca, A. Miranda, P. Morais, and S. Queirós were funded by FCT under the Ph.D. grants PD/BDE/113597/2015, SFRH/BD/52059/ 2012, SFRH/BD/95438/2013, and SFRH/BD/93443/2013, respectively.info:eu-repo/semantics/publishedVersio