Raymond Khargi, Jacob N Bamberger, Anna Ricapito, Kavita Gupta, Alan J Yaghoubian, Johnathan A Khusid, Blair Gallante, William M Atallah, Mantu Gupta
Introduction: The objective of this study is to conduct a thorough investigation of the risk factors associated with blood loss during PCNL, within the setting of a US urban tertiary care center.
Materials and methods: We conducted a retrospective analysis of our endourology database to identify adult patients who underwent PCNL for stone extraction at our tertiary stone center between October 2014 and December 2022. Patients were categorized into two groups based on the extent of blood loss: significant blood loss (SBL) and no significant blood loss (NSBL). The cut-off value for SBL was determined as the median change in hematocrit levels from preoperative to postoperative among patients who required postoperative transfusions. Several factors were evaluated, including stone dimensions, operative details, the presence of preoperative drains, patient position, type of access, access site, number of accesses, tract size, tract length, stone location, number of stones, operative time, and the S.T.O.N.E. Nephrolithometry Scoring System.
Results: Our analysis included a total of 695 procedures performed on 674 distinct patients who met our inclusion criteria. Of these, 102 patients (14.7%) were included in the SBL group. Patients in the SBL group had a higher mean number of accesses (1.57 vs. 1.29, P<0.001), were positioned prone more often (96.0% vs. 88.6%, P = 0.025), and underwent fluoroscopic-guided access more frequently (89.9% vs. 64.8%, P<0.001). Additionally, significant differences were observed in stone morphology, with the SBL group having higher rates of complete staghorn stones (42.2% vs. 27.0%, P = 0.019) and lower rates of partial staghorn stones (27.7% vs. 36.8%, P = 0.019). A larger proportion of patients in the SBL group required a 16 French nephrostomy tube for postoperative drainage (13.3% vs. 10.4%, P = 0.041). Lastly, the SBL group had a longer mean operative time compared to the NSBL group (P<0.001). Multiple logistic regression analysis identified stone volume (P = 0.039), number of accesses (P = 0.047), and operative time (P = 0.006) as independent risk factors associated with SBL status.
Conclusion: Surgical complexity factors such as stone volume, number of accesses, and operative time are linked to a higher risk of SBL during PCNL. Stone volume and the requirement for multiple accesses can usually be estimated with reasonable accuracy before surgery.
{"title":"Comprehensive analysis of factors associated with significant blood loss during percutaneous nephrolithotomy.","authors":"Raymond Khargi, Jacob N Bamberger, Anna Ricapito, Kavita Gupta, Alan J Yaghoubian, Johnathan A Khusid, Blair Gallante, William M Atallah, Mantu Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>The objective of this study is to conduct a thorough investigation of the risk factors associated with blood loss during PCNL, within the setting of a US urban tertiary care center.</p><p><strong>Materials and methods: </strong>We conducted a retrospective analysis of our endourology database to identify adult patients who underwent PCNL for stone extraction at our tertiary stone center between October 2014 and December 2022. Patients were categorized into two groups based on the extent of blood loss: significant blood loss (SBL) and no significant blood loss (NSBL). The cut-off value for SBL was determined as the median change in hematocrit levels from preoperative to postoperative among patients who required postoperative transfusions. Several factors were evaluated, including stone dimensions, operative details, the presence of preoperative drains, patient position, type of access, access site, number of accesses, tract size, tract length, stone location, number of stones, operative time, and the S.T.O.N.E. Nephrolithometry Scoring System.</p><p><strong>Results: </strong>Our analysis included a total of 695 procedures performed on 674 distinct patients who met our inclusion criteria. Of these, 102 patients (14.7%) were included in the SBL group. Patients in the SBL group had a higher mean number of accesses (1.57 vs. 1.29, P<0.001), were positioned prone more often (96.0% vs. 88.6%, P = 0.025), and underwent fluoroscopic-guided access more frequently (89.9% vs. 64.8%, P<0.001). Additionally, significant differences were observed in stone morphology, with the SBL group having higher rates of complete staghorn stones (42.2% vs. 27.0%, P = 0.019) and lower rates of partial staghorn stones (27.7% vs. 36.8%, P = 0.019). A larger proportion of patients in the SBL group required a 16 French nephrostomy tube for postoperative drainage (13.3% vs. 10.4%, P = 0.041). Lastly, the SBL group had a longer mean operative time compared to the NSBL group (P<0.001). Multiple logistic regression analysis identified stone volume (P = 0.039), number of accesses (P = 0.047), and operative time (P = 0.006) as independent risk factors associated with SBL status.</p><p><strong>Conclusion: </strong>Surgical complexity factors such as stone volume, number of accesses, and operative time are linked to a higher risk of SBL during PCNL. Stone volume and the requirement for multiple accesses can usually be estimated with reasonable accuracy before surgery.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 5","pages":"420-428"},"PeriodicalIF":1.2,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prostate cancer remains one of the most common causes of cancer-related death in men globally. Progression of prostate cancer to lethal metastatic disease is mediated by multiple contributors. The role of prostate microbiota and their metabolites in metastasis, therapeutic resistance to castration resistant prostate cancer (CRPC), and tumor relapse has yet to be fully investigated. Characterization of microflora can provide new mechanistic insights into the functional significance in the emergence of therapeutic resistance, identification of novel effective targeted therapies, and development of biomarkers during prostate cancer progression. The tumor microenvironment (TME) and its components work concurrently with the prostate microbiota in promoting prostate cancer development and progression to metastasis. In this article, we discuss the growing evidence on the functional contribution of microbiota to the phenotypic landscape of the TME and its effect on prostate cancer therapeutic targeting and recurrent disease.
{"title":"Microbiota and the landscape of the prostate tumor microenvironment.","authors":"Kasmira R Gupta, Natasha Kyprianou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer remains one of the most common causes of cancer-related death in men globally. Progression of prostate cancer to lethal metastatic disease is mediated by multiple contributors. The role of prostate microbiota and their metabolites in metastasis, therapeutic resistance to castration resistant prostate cancer (CRPC), and tumor relapse has yet to be fully investigated. Characterization of microflora can provide new mechanistic insights into the functional significance in the emergence of therapeutic resistance, identification of novel effective targeted therapies, and development of biomarkers during prostate cancer progression. The tumor microenvironment (TME) and its components work concurrently with the prostate microbiota in promoting prostate cancer development and progression to metastasis. In this article, we discuss the growing evidence on the functional contribution of microbiota to the phenotypic landscape of the TME and its effect on prostate cancer therapeutic targeting and recurrent disease.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 5","pages":"352-360"},"PeriodicalIF":1.2,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryan M Blake, Neha Malhotra, Mantu Gupta, Johnathan A Khusid
Myotonic dystrophy is a debilitating genetic disease that carries a predilection for a variety of comorbidities. Kidney stone disease in this population can present a variety of unique challenges related to patient age, comorbidities, and social factors. We present a video review case of a 13-year-old girl with myotonic dystrophy who was treated surgically for large bilateral stone burden, bilateral retained ureteral stents with nephrostomy tubes, and right ureteral stricture. The patient had multiple prior urologic procedures and recurrent admissions for infection prior to presentation. Preoperative planning included non-contrast CT imaging, admission to an intensive care unit, and multidisciplinary discussion of treatment and goals. Through combined antegrade and retrograde approaches, the patient's stone burden was cleared, right ureteral stricture was treated, and all tubes were able to be removed in two major procedures and one minor cystoscopy with stent removal under anesthesia. Early referral to tertiary care centers and involvement of multiple specialist teams may help reduce perioperative risk and minimize the number of surgeries. Additionally, patients at high anesthesia risk may benefit from concurrent percutaneous nephrolithotomy with endopyelotomy.
{"title":"Treatment of bilateral encrusted ureteral stents, large volume renal stones, and ureteral stricture in a complex pediatric patient: a surgical video and case review.","authors":"Ryan M Blake, Neha Malhotra, Mantu Gupta, Johnathan A Khusid","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Myotonic dystrophy is a debilitating genetic disease that carries a predilection for a variety of comorbidities. Kidney stone disease in this population can present a variety of unique challenges related to patient age, comorbidities, and social factors. We present a video review case of a 13-year-old girl with myotonic dystrophy who was treated surgically for large bilateral stone burden, bilateral retained ureteral stents with nephrostomy tubes, and right ureteral stricture. The patient had multiple prior urologic procedures and recurrent admissions for infection prior to presentation. Preoperative planning included non-contrast CT imaging, admission to an intensive care unit, and multidisciplinary discussion of treatment and goals. Through combined antegrade and retrograde approaches, the patient's stone burden was cleared, right ureteral stricture was treated, and all tubes were able to be removed in two major procedures and one minor cystoscopy with stent removal under anesthesia. Early referral to tertiary care centers and involvement of multiple specialist teams may help reduce perioperative risk and minimize the number of surgeries. Additionally, patients at high anesthesia risk may benefit from concurrent percutaneous nephrolithotomy with endopyelotomy.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 5","pages":"435-442"},"PeriodicalIF":1.2,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dual balloon adjustable continence therapy (DBACT) has emerged as a promising option for treating stress urinary incontinence. DBACT is a minimally invasive and easily reversible procedure in which two periurethral balloons are placed just distal to the bladder neck to increase bladder outflow resistance. The device is connected to a small titanium port placed under the scrotal or labial skin. The port is used for adjustment to balloon volume in the clinic setting, allowing for refinement and optimization of urinary continence. DBACT placement is typically performed under general anesthesia and is considered an outpatient procedure. Several studies have evaluated the effectiveness of DBACT in treating urinary incontinence, and the results are promising. DBACT was effective in 91% of patients who underwent the procedure, 80% reported a significant improvement in their symptoms, and 70% reported being completely dry after the procedure. DBACT is a safe procedure with few reported complications. The most common complication is mild pain or discomfort at the site of device placement, which usually resolves within a few days. Overall, DBACT is minimally invasive, adjustable, and highly successful in restoring urinary continence.
{"title":"Dual balloon adjustable continence therapy for urinary incontinence.","authors":"Michael P Feloney, Julie A Klock, Yuanyuan Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dual balloon adjustable continence therapy (DBACT) has emerged as a promising option for treating stress urinary incontinence. DBACT is a minimally invasive and easily reversible procedure in which two periurethral balloons are placed just distal to the bladder neck to increase bladder outflow resistance. The device is connected to a small titanium port placed under the scrotal or labial skin. The port is used for adjustment to balloon volume in the clinic setting, allowing for refinement and optimization of urinary continence. DBACT placement is typically performed under general anesthesia and is considered an outpatient procedure. Several studies have evaluated the effectiveness of DBACT in treating urinary incontinence, and the results are promising. DBACT was effective in 91% of patients who underwent the procedure, 80% reported a significant improvement in their symptoms, and 70% reported being completely dry after the procedure. DBACT is a safe procedure with few reported complications. The most common complication is mild pain or discomfort at the site of device placement, which usually resolves within a few days. Overall, DBACT is minimally invasive, adjustable, and highly successful in restoring urinary continence.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"334-338"},"PeriodicalIF":1.5,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461033/pdf/ajceu0011-0334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fernando J Garcia-Marques, Elissa Zakrasek, Abel Bermudez, Alexandra L Polasko, Shiqin Liu, Tanya Stoyanova, James D Brooks, John Lavelle, Sharon J Pitteri
After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp, and Candida spp. Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, Enterococcus, Candida spp, and P. mirabilis had greater associations with the biofilm phase, whereas E. coli and Klebsiella had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.
{"title":"Proteomics analysis of urine and catheter-associated biofilms in spinal cord injury patients.","authors":"Fernando J Garcia-Marques, Elissa Zakrasek, Abel Bermudez, Alexandra L Polasko, Shiqin Liu, Tanya Stoyanova, James D Brooks, John Lavelle, Sharon J Pitteri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: <i>Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp</i>, and <i>Candida spp</i>. Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, <i>Enterococcus, Candida spp</i>, and <i>P. mirabilis</i> had greater associations with the biofilm phase, whereas <i>E. coli</i> and <i>Klebsiella</i> had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 3","pages":"206-219"},"PeriodicalIF":1.2,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333135/pdf/ajceu0011-0206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ezidin G Kaddumi, Ali Al Khader, Abdul-Fattah S Fararjeh, Alaa A Abusamhadaneh
Background: The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet.
Methods: In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated.
Results: Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression.
Conclusion: The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes.
{"title":"The effect of vagotomy on c-fos expression in the reticular formation areas following cystometry in cyclophosphamide-induced cystitis in rats.","authors":"Ezidin G Kaddumi, Ali Al Khader, Abdul-Fattah S Fararjeh, Alaa A Abusamhadaneh","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet.</p><p><strong>Methods: </strong>In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated.</p><p><strong>Results: </strong>Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression.</p><p><strong>Conclusion: </strong>The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"40-49"},"PeriodicalIF":1.5,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009307/pdf/ajceu0011-0040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9122061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renyuan Zhang, Shalini Singh, Chunliu Pan, Bo Xu, Jon Kindblom, Kevin H Eng, John J Krolewski, Kent L Nastiuk
Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.
{"title":"Rate of castration-induced prostate stroma regression is reduced in a mouse model of benign prostatic hyperplasia.","authors":"Renyuan Zhang, Shalini Singh, Chunliu Pan, Bo Xu, Jon Kindblom, Kevin H Eng, John J Krolewski, Kent L Nastiuk","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"12-26"},"PeriodicalIF":1.5,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009314/pdf/ajceu0011-0012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9350858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: According to the favorable effects of combination therapy to provide better sedation during double-j stent removal and lack of studies investigating the sedative effect of propofol, dexmedetomidine, and midazolam during this procedure. This study aimed to compare the effects of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.
Methods: This double-blinded randomized clinical trial was conducted on 120 patients aged 18-72 who underwent double-J ureteral stent removal in Alzahra hospital, Isfahan, Iran from September to November 2021. Patients were randomly divided into 3 groups. In the first group, propofol was titrated with normal saline and was infused with a loading dose of 0.5 mg/kg and a maintenance dose of 1.5-2.5 mg/kg/h. In the second group, Dexmedetomidine was titrated with normal saline and was infused at a dose of 1 µg/kg within 10 min and then continued at 0.45-0.55 µg/kg. In third group, midazolam was titrated was infused with a loading dose of 0.05 mg/kg and a maintenance dose of 0.05 mg/kg/h. 50 mg of fentanyl was also infused in all the groups. If the patients did not reach the desired sedation level, 10 mg ketamine was infused as a rescue sedative agent for all three groups and repeated if needed in all groups.
Results: The current study was conducted on 120 patients who underwent double-J ureteral stent removal. The comparison of the sedative effect of midazolam, dexmedetomidine, and propofol showed significant differences among the three groups and was higher in the midazolam group (P=0.018). Between the three groups systolic blood pressure and mean arterial pressure was significantly lower in the propofol group (P=0.002). Heart rate was significantly lower in the dexmedetomidine group during both surgery and recovery time (P<0.001). There was no significant difference among the groups during surgery regarding oxygen saturation (P value =0.84). The intergroup comparison indicates that the mean score of surgeon satisfaction is significantly higher in the midazolam group (P-value =0.039).
Conclusion: According to this study midazolam was superior to two other groups and was associated with deeper sedation and higher satisfaction among both patient and surgeon.
{"title":"Comparison of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.","authors":"Hamidreza Shetabi, Faride Akrami Moghaddam, Reza Kazemi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>According to the favorable effects of combination therapy to provide better sedation during double-j stent removal and lack of studies investigating the sedative effect of propofol, dexmedetomidine, and midazolam during this procedure. This study aimed to compare the effects of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.</p><p><strong>Methods: </strong>This double-blinded randomized clinical trial was conducted on 120 patients aged 18-72 who underwent double-J ureteral stent removal in Alzahra hospital, Isfahan, Iran from September to November 2021. Patients were randomly divided into 3 groups. In the first group, propofol was titrated with normal saline and was infused with a loading dose of 0.5 mg/kg and a maintenance dose of 1.5-2.5 mg/kg/h. In the second group, Dexmedetomidine was titrated with normal saline and was infused at a dose of 1 µg/kg within 10 min and then continued at 0.45-0.55 µg/kg. In third group, midazolam was titrated was infused with a loading dose of 0.05 mg/kg and a maintenance dose of 0.05 mg/kg/h. 50 mg of fentanyl was also infused in all the groups. If the patients did not reach the desired sedation level, 10 mg ketamine was infused as a rescue sedative agent for all three groups and repeated if needed in all groups.</p><p><strong>Results: </strong>The current study was conducted on 120 patients who underwent double-J ureteral stent removal. The comparison of the sedative effect of midazolam, dexmedetomidine, and propofol showed significant differences among the three groups and was higher in the midazolam group (P=0.018). Between the three groups systolic blood pressure and mean arterial pressure was significantly lower in the propofol group (P=0.002). Heart rate was significantly lower in the dexmedetomidine group during both surgery and recovery time (P<0.001). There was no significant difference among the groups during surgery regarding oxygen saturation (<i>P</i> value =0.84). The intergroup comparison indicates that the mean score of surgeon satisfaction is significantly higher in the midazolam group (<i>P</i>-value =0.039).</p><p><strong>Conclusion: </strong>According to this study midazolam was superior to two other groups and was associated with deeper sedation and higher satisfaction among both patient and surgeon.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"160-167"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165230/pdf/ajceu0011-0160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Riveros, Mohammed Al-Toubat, Victor Chalfant, Ahmed Elshafei, Allison Feibus, Ana Forero, K C Balaji
Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.
{"title":"The impact of socioeconomic status on the survival of men with early-onset prostate cancer.","authors":"Carlos Riveros, Mohammed Al-Toubat, Victor Chalfant, Ahmed Elshafei, Allison Feibus, Ana Forero, K C Balaji","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"146-154"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165226/pdf/ajceu0011-0146.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods. Herein, we review the transition from traditional methods that identify individual AAbs to high throughput approaches that detect multiple targets simultaneously in patient sera. We also discuss how these approaches improved the sensitivity and specificity of AAb detection and enhanced prostate cancer diagnosis and prognosis. Cancer vaccines offer potential as a novel therapeutic strategy in their ability to stimulate both cell-mediated and antibody-mediated cytotoxic responses. Ongoing efforts aim to identify immunotherapy targets that also stimulate a strong antibody response, since antibodies activated by the anti-cancer humoral response can eliminate cancer cells effectively via several distinct mechanisms. Autoantibodies are useful not only for the diagnosis of prostate cancer, predicting disease progression, and tracking response to treatment, but can also be harnessed as therapeutic agents for prostate cancer treatment.
{"title":"Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy.","authors":"Rahul Jayakrishnan, Cara Schafer, Shyh-Han Tan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods. Herein, we review the transition from traditional methods that identify individual AAbs to high throughput approaches that detect multiple targets simultaneously in patient sera. We also discuss how these approaches improved the sensitivity and specificity of AAb detection and enhanced prostate cancer diagnosis and prognosis. Cancer vaccines offer potential as a novel therapeutic strategy in their ability to stimulate both cell-mediated and antibody-mediated cytotoxic responses. Ongoing efforts aim to identify immunotherapy targets that also stimulate a strong antibody response, since antibodies activated by the anti-cancer humoral response can eliminate cancer cells effectively via several distinct mechanisms. Autoantibodies are useful not only for the diagnosis of prostate cancer, predicting disease progression, and tracking response to treatment, but can also be harnessed as therapeutic agents for prostate cancer treatment.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"79-102"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165224/pdf/ajceu0011-0079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}