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Autophagy is being explored as a potential therapeutic target for enhancing the cytotoxic effects of chemotherapeutic regimens in various malignancies. Autophagy plays a very important role in cancer pathogenesis. Here, we discuss the updates on the modulation of autophagy via dynamic interactions with different organelles and the exploitation of selective autophagy for exploring therapeutic strategies. We further discuss the role of autophagy inhibitors in cancer preclinical and clinical trials, novel autophagy inhibitors, and challenges likely to be faced by clinicians while inducting autophagy modulators in clinical practice.
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Autofagia/fisiologia , Neoplasias/patologia , Animais , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVES: Medical expulsive therapy has been found to be effective for distal ureteric stones; however, which drug is most efficacious in terms of stone expulsion rate (SER) and stone expulsion time (SET) is not known. With this review we aimed to compare the efficacy of various drug treatments for distal ureter stones used as medical expulsive therapy in terms of SER and SET. METHODS: Systematic literature search was conducted to include all the randomised study comparing various drug interventions for lower ureter stones. Standard preferred reporting items for systematic review and meta-analysis for network meta-analysis (PRISMA-NMA) were pursued. RESULTS: In this review, 50 randomised studies with 12,382 patients were included. For stone expulsion rate (SER), compared with placebo all the treatment groups were more effective except nifedipine and sildenafil. According to the SUCRA values obtained, naftopidil plus steroid was the highest rank and nifedipine lowest. For stone expulsion time (SET), compared with placebo only tadalafil plus silodosin, nifedipine plus steroid, alfuzosin, silodosin, tadalafil and tamsulosin were more effective. SUCRA values were highest for tadalafil plus silodosin and least for naftopidil plus steroid. From subgroup analysis with individual drugs for SER, SUCRA values were highest for naftopidil followed by silodosin and SET was highest for silodosin and least for naftopidil. CONCLUSION: For lower ureter stone, tadalafil plus silodosin is the best combination and silodosin best individual drug considering the SET and SER. Nifedipine as monotherapy is no more effective than control group.
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Preparações Farmacêuticas , Ureter , Cálculos Ureterais , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Tansulosina , Resultado do Tratamento , Cálculos Ureterais/tratamento farmacológicoRESUMO
INTRODUCTION AND OBJECTIVE: The RENAL, PADUA and centrality index (C-index) nephrometry scoring systems (SS) have been individually evaluated for their role in predicting trifecta outcomes after nephron-sparing surgery (NSS). However, there is little data on their comparative superiority. The present study was designed to evaluate the predictive value of three SS and to assess interobserver reliability. MATERIALS AND METHODS: Fifty patients undergoing NSS at our center between January 2014 and April 2016 were included in the study. The demographic details were noted. Images (computed tomography [CT] scans or magnetic resonance imaging) were reviewed by a urologist and a radiologist independently and RENAL, PADUA, and C-index were calculated. The correlation between these scoring system and trifecta outcomes were calculated. RESULTS: The RENAL and PADUA score did not correlate with any of the perioperative parameters. However, C-index had a significant correlation with operative time (OT) (P = 0.02) and trifecta outcomes (P < 0.05). There was an excellent concordance between the two observers in scoring the RENAL score (α = 0.915; intraclass correlation coefficient [ICC] = 0.814) and PADUA score (α = 0.816; ICC = 0.689 [P < 0.001]). There was lesser although acceptable concordance in the calculation of C-index (ICC -0.552; α -0.711). CONCLUSIONS: There is good correlation among all the 3 SS. C-index has lower reproducibility due to difficult mathematical calculation but correlated best with trifecta outcomes.
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INTRODUCTION: The renal nephrometry scoring (RNS) system enables prediction the feasibility of nephron-sparing surgery (NSS) in renal masses. There is insufficient data regarding the outcome of robot-assisted NSS in tumors with RNS ≥10. We reviewed the trifecta outcomes of patients undergoing robotic NSS with high RNS and compare it with tumors of low and intermediate RNS. MATERIALS AND METHODS: Our prospectively maintained data of all robot-assisted NSS were reviewed, and those with RNS of ≥10 were identified. Patient data, outcomes and postoperative estimated glomerular filtration rate were compared between high, intermediate and low RNS patients. RESULTS: In high RNS group, the mean age of the patients was 53 years (male:female = 15:3). Mean diameter of tumors was 6.28 cm (3.0-10.5 cm). Mean operative time was 173.61 ± 52.66 min and mean warm ischemia time was 27.85 ± 5.27 min. Mean estimated blood loss (EBL) was 363.89 ± 296.45 ml. Mean hospital length of stay was 5.39 ± 1.91 days (3-9 days). When compared with low and intermediate RNS, only EBL and need for pelvicalyceal system repair was significantly higher in high RNS group. Postoperative complications, renal function preservation and oncological outcomes at 3 months were comparable in all the three groups. CONCLUSION: Robot-assisted NSS is feasible with comparable outcomes in tumors with high RNS.
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Migration of Ascaris from intestine into peritoneal cavity is rare and usually presents as acute abdomen. We report a case of 41-year-old male who was admitted for laparoscopic mesh rectopexy for rectal prolapse. During the initial laparoscopy, purulent fluid was seen in pelvis. A complete diagnostic laparoscopy was done. An omental nodule was found, which was excised and extracted in a bag. On histopathology, the omental nodule revealed gravid Ascaris lumbricoides.
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Benign nerve sheath tumours such as schwannomas commonly involve the peripheral and cranial nerves. A schwannoma in the adrenal gland is a very rare occurrence, which arises from the adrenal medulla. Its most common presentation is a non-functional incidentaloma. It does not have any unique imaging characteristic distinguishing it from other adrenal masses; hence, its diagnosis is usually confirmed by final histopathology. In this report, we present two cases of an adrenal schwannoma for which we anticipated an unusual diagnosis, which was confirmed through adrenalectomy on histopathology.
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OBJECTIVE: To study the effect of 3 antioxidants viz. selenium, carnitine and coenzyme Q10, alone or in combination, on both semen parameters and pregnancy rates in couples with male factor infertility. METHODS: Using PRISMA guidelines, a systematic search was performed of the PubMed, Scopus, EMBASE, and Web of Science databases for randomized studies comparing selenium, carnitine or coenzyme Q10 with placebo in the treatment of male infertility and reporting semen and pregnancy outcomes. RESULTS: A total of 3304 studies were screened of which 20 were included. The study protocol was registered with PROSPERO (CRD42020210284). Pregnancy rate in the treatment group (69/426, 16.2%) was not different from the placebo (45/401, 11.2%) (Pâ¯=â¯.05). Treatment group showed higher motility [mean difference 5.05, 95% CI (2.77, 7.34), P =<.0001], progressive motility [mean difference 5.72, 95% CI (2.77, 8.66), Pâ¯=â¯.0001], sperm concentration [mean difference 6.58, 95% CI (3.22, 9.93), Pâ¯=â¯.0001] than placebo. CONCLUSION: Although antioxidants and their combinations are associated with improvement in sperm concentration, motility, and semen volume, the differences are small. There is no difference in pregnancy rates between patients receiving selenium, carnitine, and coenzyme Q10, or placebo. The quality of studies is poor, limiting the level of evidence.
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Infertilidade Masculina , Selênio , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carnitina/farmacologia , Carnitina/uso terapêutico , Feminino , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Gravidez , Selênio/farmacologia , Selênio/uso terapêutico , Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Ubiquinona/análogos & derivadosRESUMO
Major fraction of the human genome is transcribed in to the RNA but is not translated in to any specific functional protein. These transcribed but not translated RNA molecules are called as non-coding RNA (ncRNA). There are thousands of different non-coding RNAs present inside the cells, each regulating different cellular pathway/pathways. Over the last few decades non-coding RNAs have been found to be involved in various diseases including cancer. Non-coding RNAs are reported to function both as tumor enhancer and/or tumor suppressor in almost each type of cancer. Urothelial carcinoma of the urinary bladder is the second most common urogenital malignancy in the world. Over the last few decades, non-coding RNAs were demonstrated to be linked with bladder cancer progression by modulating different signalling pathways and cellular processes such as autophagy, metastasis, drug resistance and tumor proliferation. Due to the heterogeneity of bladder cancer cells more in-depth molecular characterization is needed to identify new diagnostic and treatment options. This review emphasizes the current findings on non-coding RNAs and their relationship with various oncological processes such as autophagy, and their applicability to the pathophysiology of bladder cancer. This may offer an understanding of evolving non-coding RNA-targeted diagnostic tools and new therapeutic approaches for bladder cancer management in the future.
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BACKGROUND: The present study aims to assess the efficacy of mirabegron, a novel beta-3 agonist for ameliorating stent related symptoms (SRSs) as compared to tamsulosin and solifenacin. METHODS: Total of 150 patients undergoing ureteral stent placement following ureteroscopic lithotripsy, percutaneous nephrolithotomy, or laparoscopic/robotic pyeloplasty were randomized in 1:1:1 fashion to receive mirabegron 50 mg (group A), solifenacin 5 mg (group B), and tamsulosin 0.4 mg (group C) OD respectively. Patients were followed at POD10 (I visit), 4 weeks (II visit) after surgery, and 2 weeks post-stent removal. Validated vernacular version of ureteric stent symptoms questionnaire (USSQ) was administered to the patients at each visit. RESULTS: Out of 150 patients randomized, 123 patients (A; n = 41, B; n = 40, and C; n = 42) completed the study. The groups were comparable in terms of urinary index score of USSQ at I and II visits (p = 0.119 and 0.076, respectively). A lower proportion of patients in group B experiencing bodily pain at II visit (p = 0.039), however, pain scores were comparable. Significantly lower general health index scores were observed in group A at I visit and over 4 weeks (p = 0.007). No significant differences were observed in other domains of USSQ. Age, sex, and surgical procedure undertaken did not significantly impact the scores in various USSQ domains. CONCLUSION: Mirabegron demonstrates comparable benefit in alleviating SRSs with better general health indices and may be an effective alternative for SRSs, especially when tamsulosin or solifenacin are contra-indicated or poorly tolerated.
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Succinato de Solifenacina , Agentes Urológicos , Acetanilidas , Humanos , Dor , Estudos Prospectivos , Qualidade de Vida , Succinato de Solifenacina/uso terapêutico , Stents , Tansulosina/uso terapêutico , Tiazóis , Resultado do Tratamento , Agentes Urológicos/uso terapêuticoRESUMO
BACKGROUND: There is an ongoing need and search for a simple yet accurate nephrometry scoring system for predicting the postoperative outcomes after partial nephrectomy (PN). Simplified PADUA Renal (SPARE) Nephrometry Scoring System, a simplified version of Preoperative Aspects and Dimensions Used for an Anatomical Classification (PADUA) has been proposed as a predictor of postoperative complications following PN recently. However, this score has never been externally validated and assessed as a predictor of trifecta and pentafecta outcomes of PN. In the current study, we applied the SPARE scoring system to our robot-assisted PN cohort (RAPN). METHODS: Prospectively maintained data of patients, who underwent RAPN from November 2014 to December 2018, was abstracted. Imaging was analyzed to calculate SPARE and RENAL nephrometry scores (RNS) by two urologists, independently. SPARE was compared with complications, trifecta outcomes, pentafecta outcomes, and RENAL nephrometry scoring (RNS). RESULTS: Data of 201 RAPN patients were analyzed. The mean SPARE score was 3 (range 0-11). One hundred thirteen patients were classified as low risk, 64 as intermediate risk, and 24 as high risks. On multivariate analysis SPARE score alone predicted complications (OR=1.37, P=0.014) and trifecta outcomes (OR=0.75, P=0.000) while age (OR=0.96, P=0.042), preoperative eGFR (OR=0.97, P=0.001) and SPARE scores (OR=0.81, P=0.016) were predictors for pentafecta outcomes. Receiver operated curve (ROC) analysis between SPARE and RNS in predicting the complications; trifecta and pentafecta outcomes had a comparable area under the curve. CONCLUSIONS: Our study validates the SPARE nephrometry scoring system in predicting postoperative complications, trifecta, and pentafecta outcomes in a RAPN cohort. The predictive accuracy of SPARE is similar to RNS.
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Neoplasias Renais , Robótica , Humanos , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: Instrument-related complications occur occasionally with the use of flexible ureteroscopes. In this study, we present a unique problem related to instrument malfunction of flexible ureteroscope during retrograde intrarenal surgery. Case Presentation: A 60-year-old male patient with a 1.2 cm left upper ureteral stone initially underwent semirigid ureteroscopic laser lithotripsy and during the procedure the stone got retropulsed into middle calix of the kidney. Subsequently, a 9.5F (internal diameter) ureteral access sheath was placed and using URF P6R flexible ureteroscope (Olympus) the stone was completely dusted with holmium laser. At the end of the procedure, the operating surgeon was unable to remove the ureteroscope out of the ureteral access sheath as it was getting stuck inside. On careful inspection under fluoroscopy, it was noticed that there was a partial break in the outer surface of the flexible ureteroscope at the level of the junction of the distal flexible part of the ureteroscope with the shaft. Since multiple attempts to retrieve the ureteroscope into the access sheath failed, a decision was made to pull the ureteroscope and ureteral access sheath as a whole over a 0.035â³ terumo guidewire. Gentle traction was applied on the entire assembly and the instrument was withdrawn out of ureter over the guidewire under fluoroscopic guidance. A lateral angulation of the distal flexible portion with the shaft of the flexible ureteroscope caused by breakage of the fiber-optic cables led to this problem intraoperatively. Conclusion: Breakage of fiber-optic cables caused by excessive manipulation of flexible ureteroscope during retrograde intrarenal surgery can lead to entrapment of the ureteroscope within the ureteral access sheath. This problem might be solved by gently withdrawing the whole assembly out of the ureter over a guidewire.
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Bladder pheochromocytoma is the most common extra-adrenal genitourinary tumor. Endoscopic management is feared due to the risk of intra-operative hypertensive crisis. We described a case of successful endoscopic management of a bladder pheochromocytoma and discussed its technical aspects.
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The management of complex pelvic-ureteric junction obstruction (PUJO) is challenging. The traditional open surgical approach used large incisions with prolonged post-operative recovery. Laparoscopic reconstruction in complex PUJO requires surgical expertise and is challenging to master. Robotic assistance has provided a viable minimally invasive alternative replicating the open surgical approach for such complex cases. In the present study, we evaluated the feasibility and success of robot-assisted reconstructive procedures in such situations.
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Pelve Renal/cirurgia , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Ureter/cirurgia , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adulto , Constrição Patológica , Estudos de Viabilidade , Feminino , Humanos , Hidronefrose/etiologia , Hidronefrose/cirurgia , Pelve Renal/patologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ureter/patologia , Obstrução Ureteral/complicaçõesRESUMO
Isolated renal mucormycosis in immunocompetent hosts is a rare entity. We present the largest case series of isolated renal mucormycosis in immunocompetent hosts. Retrospective data of isolated renal mucormycosis from March 2012 to June 2017 was reviewed. Fifteen patients of isolated renal mucormycosis were identified. Contrast-enhanced computed tomography scan showed enlarged globular kidneys with decreased or patchy enhancement, perinephric stranding and thickened Gerota's fascia in all patients. Ten patients with unilateral involvement underwent nephrectomy and two of four patients with bilateral renal mucormycosis underwent bilateral nephrectomy. Two patients were managed with intravenous antifungal therapy alone. Overall, the mortality rate in our series was 40% (6/15). Isolated renal mucormycosis in healthy immunocompetent hosts is an emerging new entity. Prompt diagnosis based on the characteristic clinical and radiological picture and starting high-dose antifungal therapy at least 24 hours before surgical debridement offer the best chance of survival in these patients.
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Imunocompetência , Nefropatias/microbiologia , Mucormicose/tratamento farmacológico , Adolescente , Adulto , Antifúngicos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/microbiologia , Rim/patologia , Nefropatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Mucormicose/mortalidade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Purpose: RENAL nephrometry score (RNS) was devised for deciding the approach for renal tumors. It is increasingly used in predicting perioperative outcomes with variable results. The actual difficulty encountered during surgery depends on a number of other variables. The main purpose of this prospective study was to identify these variables which are not addressed by current RNS. Materials and Methods: Forty-nine patients undergoing robotic nephron sparing surgery from January 2015 onward were included. RNS was calculated from the imaging. Operating surgeon rated each surgery on a Likert scale of 0-4 after the completion of the procedure. The questionnaire was pre-validated in 5 cases before administration. The correlation between the surgeon rating and RNS with perioperative parameters and trifecta outcomes were calculated. Results: Forty-seven percent surgeries were rated easy, and 53.0% were rated as difficult. Surgeries for hilar, posterior location and presence of supernumerary vessels were found to be the a cause of difficulty. Trifecta outcomes were achieved in 37/49 patients (75.5%). The mean rating was 2.580±0.900 in trifecta negative patients while it was 1.410±0.832 in trifecta positive patient (p<0.0001). Surgeon's rating correlated positively with trifecta outcomes (likelihood ratio=15.75, p=0.006). Conclusions: The RNS remained a useful tool for determining renal tumor complexity. The intraoperative difficulty faced by the surgeon can be rated which can better predict perioperative trifecta outcomes. A useful predicting tool can be developed using the two parameters (RNS and surgeon rated difficulty).
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Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Tratamentos com Preservação do Órgão , Adulto , Atitude do Pessoal de Saúde , Perda Sanguínea Cirúrgica , Competência Clínica , Feminino , Humanos , Laparoscopia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Néfrons , Duração da Cirurgia , Período Pré-Operatório , Estudos Prospectivos , Curva ROC , Procedimentos Cirúrgicos Robóticos , Resultado do Tratamento , Isquemia QuenteRESUMO
The da Vinci(TM) robotic system (Intuitive Surgical, Inc, Sunnyvale, CA) has been used frequently for urological procedures including radical prostatectomy and pyeloplasty. Its use in bariatric surgery is limited to few high volume centres in the western world. The advantages of robotic assistance are three-dimensional vision, ergonomic advantage and improved precision. We report our experience of using this advanced technology to perform a robotic Roux-en-Y gastric bypass in a 55-year-old obese diabetic patient. We were able to reproduce our standard laparoscopic technique and all the steps of the surgical procedure were done using robotic assistance.