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Abstract Background Partial nephrectomy (PN) has become the dominant treatment modality for cT1 renal tumor lesions. Tumors suspected of malignant potential are indicated for surgery, but some are histologically classified as benign lesions after surgery. This study aims to analyze the number of benign findings after PN according to definitive histology and to evaluate whether there is an association between malignant tumor findings and individual factors. Methods The retrospective study included 555 patients who underwent open or robotic-assisted PN for a tumor in our clinic from January 2013 to December 2020. The cohort was divided into groups according to definitive tumor histology (malignant tumors vs. benign lesions). The association of factors (age, sex, tumor size, R.E.N.A.L.) with the malignant potential of the tumor was further evaluated. Results In total, 462 tumors were malignant (83%) and 93 benign (17%). Of the malignant tumors, 66% were clear-cell RCC (renal cell carcinoma), 12% papillary RCC, and 6% chromophobe RCC. The most common benign tumor was oncocytoma in 10% of patients, angiomyolipoma in 2%, and papillary adenoma in 1%. In univariate analysis, there was a higher risk of malignant tumor in males (OR 2.13, 95% CI 1.36–3.36, p = 0.001), a higher risk of malignancy in tumors larger than 20 mm (OR 2.32, 95% CI 1.43–3.74, p

A human induced pluripotent stem cell line was generated from cancer-associated fibroblasts of a 68-years old patient with diagnosed prostate adenocarcinoma (PCa). The fibroblast cell line was reprogrammed with Epi5™ Episomal iPSC Reprogramming Kit. Pluripotency of the derived transgene-free iPS cell line was confirmed both in vitro by detecting expression of factors of pluripotency on a single-cell level, and also in vivo using teratoma formation assay. This new iPS cell line may be used for differentiation into different prostate-specific cell types in differentiation studies.

Background: Partial nephrectomy (PN) has become the dominant treatment modality for cT1 renal tumor lesions. Tumors suspected of malignant potential are indicated for surgery, but some are histologically classified as benign lesions after surgery. This study aims to analyze the number of benign findings after PN according to definitive histology and to evaluate whether there is an association between malignant tumor findings and individual factors. Methods: The retrospective study included 555 patients who underwent open or robotic-assisted PN for a tumor in our clinic from January 2013 to December 2020. The cohort was divided into groups according to definitive tumor histology (malignant tumors vs. benign lesions). The association of factors (age, sex, tumor size, R.E.N.A.L.) with the malignant potential of the tumor was further evaluated. Results: In total, 462 tumors were malignant (83%) and 93 benign (17%). Of the malignant tumors, 66% were clear-cell RCC (renal cell carcinoma), 12% papillary RCC, and 6% chromophobe RCC. The most common benign tumor was oncocytoma in 10% of patients, angiomyolipoma in 2%, and papillary adenoma in 1%. In univariate analysis, there was a higher risk of malignant tumor in males (OR 2.13, 95% CI 1.36–3.36, p = 0.001), a higher risk of malignancy in tumors larger than 20 mm (OR 2.32, 95% CI 1.43–3.74, p < 0.001), and a higher risk of malignancy in tumors evaluated by R.E.N.A.L. as tumors of intermediate or high complexity (OR 2.8, 95% CI 1.76–4.47, p < 0.001). In contrast, there was no association between older age and the risk of malignant renal tumor (p = 0.878). Conclusions: In this group, 17% of tumors had benign histology. Male sex, tumor size greater than 20 mm, and intermediate or high R.E.N.A.L. complexity were statistically significant predictors of malignant tumor findings. [ABSTRACT FROM AUTHOR]

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IntroductionPlatinum-based chemotherapy followed by the immune checkpoint inhibitor avelumab represents an intensified upfront therapy regimen that may result in significant downstaging and, subsequently, potentially radical robotic nephroureterectomy with a lymph node dissection, an uncommon approach with an unexpectedly favorable outcome.Case presentationWe report a case of a 70-year-old female presented with a sizeable cN2+ tumor of the left renal pelvis and achieved deep partial radiologic response after systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance therapy and subsequent robotic resection of the tumor. The patient continued with adjuvant nivolumab therapy once recovered after surgery and remained tumor-free on the subsequent follow-up. The systemic treatment was without any severe adverse reaction.ConclusionWe highlight the feasibility of the upfront systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance, robotic-assisted removal of the tumor, and adjuvant immunotherapy with nivolumab. This intensification of the upfront systemic therapy, and the actual treatment sequence significantly increase the chances of prolonged survival or even a cure. This type of personalized therapeutic approach can accelerate future advanced immunotherapeutic strategies.

Simple Summary: Renal cell carcinoma (RCC) is among the most common cancer types in both men and women, and its early detection significantly improves survival. Minimally-invasive blood- or urine-based tests may increase the RCC detection rate, especially before patients develop symptoms. Here, we report significant changes in concentrations of sulfatides and sphingomyelins in plasma and urine in RCC patients compared to healthy controls. For the first time, we present findings that similar alterations appear in the lipid profiles of body fluids and tissues in patients. We observe gradual changes in sulfatide and sphingomyelin concentrations with increasing tumor stage and grade. We built binary classifiers that detect RCC based on plasma and urine lipidome dysregulations, and we show that the plasma lipidome alterations enable distinguishing between early-stage RCC and controls. Our results demonstrate the considerable potential of lipid screening in biofluids for RCC detection and monitoring in clinical settings. Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models. [ABSTRACT FROM AUTHOR]

Copyright of Czech Urology / Ceska Urologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Študent V ml., Študentová H. Cytoreductive nephrectomy: identifying an ideal candidate based on preoperative predictive factors. Treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in recent years. Targeted therapy (TT) and, more recently, immuno‑ therapy in the form of immune checkpoint inhibi‑ tors (ICIs) have brought about a dramatic prolon‑ gation of the overall survival (OS) of patients. The urologist‘s role in mRCC is associated with cytore‑ ductive nephrectomy (CN), which aims to alleviate symptoms or prolong OS. The oncological benefits of CN have recently been questioned through two prospective randomized studies, CARMENA and SURTIME. The situation is less clear today because all retrospective studies have confirmed the onco‑ logical importance of CN in the treatment of TT, but a new systemic treatment for mRCC is being used (ICIs). The main problem remains the correct selection of patients suitable for CN. At the time of TT, it was already clear that CN is not beneficial for all patients with mRCC. This article aims to present individual preoperative factors that could help in the correct selection of CN and discuss the surgical aspects of CN execution. [ABSTRACT FROM AUTHOR]

Copyright of Urologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Urologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Urologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Peroperative histology (IFS) during robot-assisted radical prostatectomy (RARP) is used to ensure better oncological outcomes of surgery and, thanks to the possibility of safer nervesparing surgery (NS), which could improve functional outcomes such as continence. and erection. Aim: This work aims to develop our own IFS technique, verify its feasibility and describe its peroperative results in patients indicated for RARP with extended pelvic lymphadenectomy (ePLND). Materials and methods: From September 2020 to May 2021, 21 RARPs with ePLNDs were performed with IFS (intervention group). The control group (n = 42) was selected from a database of patients with RARP with ePLND without IFS operated on between December 2019 and May 2021. The control group was assigned in a 2: 1 ratio based on age, body mass index (BMI), and risk classification groups for biochemical recurrence (EAU risk groups). The IFS technique was developed, its reliability and effect on the length of the operation, the number of positive surgical margins (PSM), and the extended PSM (ePSM, defined as PSM in multiple locations or PSM one location with a length greater than 3 mm) were verified. In the case of a positive finding on IFS, periprostatic tissue resection was performed. Baseline and perioperative results were evaluated in both groups. Results: The two groups did not differ in preoperative and pathological characteristics. The duration of surgery was longer in the intervention group (median 176 minutes, interquartile range - IQR 151-183 vs. 145 minutes, IQR 133-164, p = 0.0003). The time from specimen removal to reporting the IFS result was 55 minutes (median), IQR 52-64 minutes. The number of patients with a positive margin (PSM) was in the intervention group 6 (28,6%), while only three patients (14.3%) had an ePSM finding. In the control group, 18 patients with PSM were described (42%), while in 3 (7.1%), ePSM was found. Although the groups did not differ in the total number of PSM (p = 0.593), in the control group, there was a smaller number of patients with ePSM (p = 0.031). The degree of agreement of IFS with the definitive histopathological finding was 90.5%. The percentage of complete removal of the tumor by secondary resection was 28.6%. Conslusion: We have demonstrated the feasibility of IFS in RARP with ePLND in the Czech healthcare system. IFS showed good agreement with the definitive histopathological evaluation. It is associated with longer operation time. IFS did not improve overall PSM in this cohort but contributed to complete tumor resection in one-third of PSM patients. This feasibility study helped to gain experience with IFS and led to the launch of another study with more patients. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: In this video we present our experience with robot-assisted pyeloplasty (RAP). Our first experience with laparoscopic pyeloplasty dates back to 2006. RAP brings several subjective advantages such as 3D vision and greater dexterity of laparoscopic instruments, which facilitates especially the reconstruction phase of the surgery. Material: Between March 2014 and August 2018, we performed 50 RAPs. The first 47 cases were done using 2nd generation DaVinci® S™ system. Now we work with 4th generation DaVinci® Xi™ system. Using the transperitoneal approach we start with open access for the 30° laparoscope. We use four 8mm trocars for robotic arms and one 12mm trocar for the assistant. In some patients we use transmesocolic approach. The ureter is then identified and traced cranially towards the kidney. The renal pelvis is exposed to enable dismembered pyeloplasty. We either resect the stenotic part of the proximal ureter or we place the ureter ventrally to the crossing vessels (if present). In case of large hydronephrosis the renal pelvis can be resected. Reconstruction is usually done using 6–0 Monocryl™ suture. In all patients we use the DJ stent, which is kept in place for 4 weeks. We do not always place a drain next to the kidney (ERAS principle), only in case of largely resected pelvis or inflammatory changes of surrounding tissues. The surgery is done in a standard general anaesthesia with commonly used postoperative analgesics. Ultrasound of the kidneys (US) in 2 and 9 months after surgery, diuretic scintigraphy one year post operatively and subsequent US every 6–12 months is done during the follow up. Presented case: A 29-year-old female patient was diagnosed with a right hydronephrotic kidney. The CT showed a primary hydronephrosis with no stone and significant delay in contrast excretion during the excretory phase, the cortical renal scan showed 47% split renal function of the affected kidney. Pre-stenting was done for significant loin pain. We performed transmesocolic RAP. We found accessory crossing vessels during the surgery. The renal pelvis was not resected and the anastomosis was done mostly using 6–0 Monocryl™ suture. The DJ stent was placed for 4 weeks. The console time was 93 minutes and there were no intra- and peri-operative complications. Results: Twenty-five women and 25 men with mean age 50 (median 31) were included. Rightsided pyeloplasty was done in 58% of patients. Pre-stenting was done in 38% of patients. Pain was the presenting symptom in 70% patients and recurrent UTI was present in 14% of patients. Mean console time was 88 min (36–153) and blood loss was in all patients negligible. Crossing vessels were found in 66% of patients. There were no intraoperative complications in this group. Postoperative complications were present in 4 cases (three Clavien II and one Clavien IIIb). The most serious complication was bleeding from a trokar incision that required surgical intervention. Mean follow up time was 15.3 months. The success rate (relief of symptoms, improvement of obstruction seen on scintigraphy, therefore no need for subsequent surgery) was 98% of cases. Conclusion: Robot-assisted pyeloplasty is an effective minimally invasive method for correction of ureteropelvic junction obstruction. It is usually associated with lasting resolution of obstruction in most of the patients. [ABSTRACT FROM AUTHOR]

Antenatal hydronephrosis, dilatation of the upper urinary tract (UUTD), is a common finding on prenatal ultrasound. One of the most common causes is ureteropelvic junction (UPJ) obstruction. Although such prenatally diagnosed UUTD resolves spontaneously in most newborns, further examination of these children is advocated to prevent possible irreversible kidney damage, and ultrasound is mainly used for this. If the dilatation persists or becomes symptomatic, it is necessary to proceed to other relatively demanding and invasive diagnostic examinations for these small patients, where the question of the right timing of indications for possible surgical solutions is still unclear. For this reason, various biomarkers have been investigated in a number of clinical trials as potential mini-invasive diagnostic tools for determining when upper urinary tract dilatation in such children poses a threat to the developing kidneys and they should be operated on, and vice versa, when to proceed conservatively. The aim of this article is to review the findings on and current issues with the use of biomarkers in the diagnosis and treatment of UPJ obstruction in children.

IntroductionNeoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.MethodsWe report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal.ResultsCurrently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term.ConclusionHerein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.

Background: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. Patient and Methods: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. Results: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. Conclusion: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.

Copyright of Urologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract A human induced pluripotent stem cell line was generated from cancer-associated fibroblasts of a 68-years old patient with diagnosed prostate adenocarcinoma (PCa). The fibroblast cell line was reprogrammed with Epi5™ Episomal iPSC Reprogramming Kit. Pluripotency of the derived transgene-free iPS cell line was confirmed both in vitro by detecting expression of factors of pluripotency on a single-cell level, and also in vivo using teratoma formation assay. This new iPS cell line may be used for differentiation into different prostate-specific cell types in differentiation studies. [ABSTRACT FROM AUTHOR]

Abstract: The identification of fibroblasts and cancer‐associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast‐specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti‐fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor‐derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF‐1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer‐derived (breast‐cell lines MCF 10A, HMLE and prostate‐cell lines BPH‐1, DU 145, and PC‐3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial‐to‐mesenchymal transition in response to treatment with TGF‐β1. To prove the co‐expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co‐expression of anti‐fibroblast and fibroblast surface protein on CD31/CD45‐negative/EpCAM‐positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti‐fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]