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Purpose: This retrospective cohort study assessed semen and testicular tissue quality from adult and adolescent cancer patients who had samples cryopreserved in the Cryobank of Charité-Universitätsmedizin before and/or after cancer treatment. Methods and Materials: Medical and cryopreservation data for all samples stored between 03/2004 and 05/2019 were collected retrospectively. Results: We included information on 601 samples cryopreserved from 506 cancer patients for whom oncologic treatment data were available. The majority of the samples were cryopreserved prior to cancer treatment (460/600, 77%, median 5 days before treatment). Semen quality had a predisposed reduction in those collected from adolescents with testicular and/or hematological malignancies. Analyses of the 140 (23%) samples cryopreserved after treatment initiation (median of 84 days) revealed decreased median concentration and motility following high gonadotoxic-risk treatment. Rate of oligoasthenozoospermia was comparable in samples collected prior to treatment with those provided during follow-up spermiograms within 1 year after treatment initiation (45.5% vs 45.5%). However, an increase was seen in samples collected 1-2 (9.1% to 90.9%) and 2-3 (50.0% to 100.0%) years after treatment initiation. Conclusion: Cancer diagnosis and treatment may impair spermatogenesis; therefore, patient counseling prior to cancer treatment by an oncologist and/or fertility specialist is crucial.
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Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.
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Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials.
Subject(s)
Calcitriol , Prostatic Neoplasms , Vitamin D , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Humans , Male , Vitamin D/metabolism , Vitamin D/pharmacology , Vitamin D/therapeutic use , Calcitriol/pharmacology , Calcitriol/metabolism , AnimalsABSTRACT
BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.
Subject(s)
B7-H1 Antigen , Carcinoma, Transitional Cell , Immune Checkpoint Inhibitors , Neoplasm Invasiveness , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , B7-H1 Antigen/analysis , B7-H1 Antigen/biosynthesis , Male , Female , Prognosis , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/metabolism , Aged , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Aged, 80 and over , Retrospective StudiesABSTRACT
PURPOSE: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity. METHODS: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports. RESULTS: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004). CONCLUSION: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity.
Subject(s)
Kidney , Nephrectomy , Humans , Retrospective Studies , Nephrectomy/adverse effects , Transplantation, Homologous , Graft SurvivalABSTRACT
PURPOSE: Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in grafts can be challenging. In the present study, we investigated the impact of ligation versus anastomosis of small accessory graft arteries on the perioperative outcome. METHODS: Clinical and radiological outcomes of 51 patients with MRA out of a total of 308 patients who underwent LDKT with MRA between 2011 and 2020 were stratified in two groups and analyzed. In group 1 (20 patients), ligation of accessory arteries (ARAs) and group 2 (31 patients) anastomosis of ARAs was performed. RESULTS: Significant differences were observed in the anastomosis-, surgery-, and warm ischemia time (WIT) in favor of group 1. Students t-test showed comparable serum creatinine levels of 2.33 (± 1.75) to 1.68 (± 0.83) mg/dL in group 1 and 2.63 (± 2.47) to 1.50 (± 0.41) mg/dL in group 2, were seen from 1 week to 1 year after transplant. No increased rates of Delayed graft function (DGF), primary transplant dysfunction and transplant rejection were seen, but graft loss and revision rates were slightly higher when the ARAs were ligated. Analysis of Doppler sonography revealed that segmental perfusion deficits tend to regenerate during the clinical course. CONCLUSION: Ligation of smaller accessory renal arteries may not affect the outcome of living kidney transplantation, except for a minor increase in the reoperation rate. Segmental perfusion deficits of the graft seem to regenerate in most cases as seen in Doppler sonography.
Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Renal Artery/surgery , Living Donors , Retrospective Studies , Graft Survival , Kidney/diagnostic imaging , Kidney/surgery , Kidney/blood supply , Treatment OutcomeABSTRACT
BACKGROUND: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder. METHODS: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data. RESULT: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers. CONCLUSIONS: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/pathology , Urinary Bladder/pathology , Uroplakin Ia/metabolism , Uroplakin Ib/metabolism , Biomarkers, Tumor/metabolismABSTRACT
Objective: We investigated whether pathological outcomes improved with experience and surgeon generation after robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: The study included 1338 patients who underwent RALP between February 2010 and April 2020. We created learning curves for pelvic lymph node dissection (PLND), number of lymph nodes (LNs) removed, and positive surgical margin (PSM) after adjustment for confounders. We compared the outcomes between the first and second generation of surgeons in regression models. Results: The learning curve regarding PLND indications showed a significant increase with experience for the first generation, whereas the second generation had a learning curve that remained flat at a higher level (92.3%) and significantly better than the first generation (p < 0.001). Similarly, the number of LN removed showed a significant increase with experience in both generations, but the overall median number of LN removed was significantly higher in the second generation compared with the first generation (12 vs 10, p < 0.001). However, the learning curve for PSM remained flat at â¼20% after adjustment and did not show improvement with experience in both generations of surgeons (p = 0.794). Conclusions: Surgeons showed improvement with experience and education with RALP with respect to the indications for PLND and number of LNs removed. However, there was no improvement over time and generations for PSM. Experience based solely on the number of patients operated on is not an intrinsic factor in the pathological quality of RALP. Factors other than experience may also play a role in oncologic improvement.
Subject(s)
Laparoscopy , Robotics , Male , Humans , Prostatectomy/methods , Lymph Node Excision/methods , Lymph Nodes/pathology , Laparoscopy/methodsABSTRACT
Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. Methods: To evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. Results: The staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis. Conclusion: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.
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There are limited and discrepant data on prostate cancer (PCa) and vitamin D. We investigated changes in three vitamin D3 metabolites in PCa patients after prostatectomy with zoledronic acid (ZA) treatment regarding their metastasis statuses over four years. In 32 patients from the ZEUS trial, 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 were measured with liquid chromatography coupled with tandem mass spectrometry at four time points. All the patients received daily calcium and vitamin D3. Bone metastases were detected in 7 of the 17 ZA-treated patients and in 5 of the 15 controls (without ZA), without differences between the groups (p = 0.725). While 25(OH)D3 and 24,25(OH)2D3 increased significantly after the study's start, with following constant values, the 1,25(OH)2D3 concentrations remained unchanged. ZA treatment did not change the levels of the three metabolites. 25(OH)D3 and 24,25(OH)2D3 were not associated with the development of bone metastases. In contrast, 1,25(OH)2D3 was also higher in patients with bone metastasis before the study's start. Thus, in high-risk PCa patients after prostatectomy, 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 were not affected by supportive ZA treatment or by the development of metastasis over four years, with the exception of 1,25(OH)2D3, which was constantly higher in metastatic patients. There might be potential prognostic value if the results can be confirmed.
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Introduction: Detrusor injection with onabotulinumtoxin A (OnabotA-DI) is an established therapy for overactive bladder (OAB). Little is known about the exact onset and course of the effect in the days after the injection therapy. By using a new type of app-controlled automated diary pod, for the first time, the precise onset of the effect of OnabotA-DI can be documented in real time. Materials and methods: Patients due for OnabotA-DI were asked to document voiding 3 days before and up to 3 weeks after therapy using the Diary Pod app. The detrusor injection was performed with onabotulinumtoxin A (Botox®), 100 units, at 20 sites of the detrusor muscle in a standardized manner. Voiding on the injection day itself was not documented. Results: A total of 17 patients (15 women, 2 men; aged 33−83 (mean 64.6; median 70) years) were included in the study. The handling of the Diary Pod app was user-friendly, and elderly patients did not encounter technical problems. The results of patients with reliably documented micturitions showed a continuous reduction in micturition frequency every day from the first day and significantly from day 5. For 24 h voiding, from 12.83 ± 5.54 in the 3 days before injection, the following mean values were found with significant (p < 0.05) changes after the intervention: 9.17 ± 3.19 on day 5, 8.75 ± 3.69 on day 10, 7.17 ± 2.04 on day 15, and 5.75 ± 0.5 on day 20. These changes were in similar proportions during the daytime and nighttime. Conclusions: Contrary to previous knowledge, the effect of the OnabotA-DI set in from the first postoperative days and was reflected a similar extent in day and night micturition. This study is the first to document the onset of action of OnabotA-DI in real time.
Subject(s)
Botulinum Toxins, Type A , Neuromuscular Agents , Urinary Bladder, Overactive , Aged , Male , Humans , Female , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/pharmacology , Urinary Bladder, Overactive/drug therapy , Urination , Injections , Muscles , Urodynamics , Neuromuscular Agents/therapeutic useABSTRACT
PURPOSE: Surgical treatment of patients with renal cell carcinoma (RCC) and an extended tumour thrombus (TT) in the inferior vena cava (IVC) is challenging and often requires a multidisciplinary approach. The aim of this study was to analyse results in the real-world management of RCC patients with an extended IVC TT (level II-IV according to the Mayo classification of macroscopic venous invasion in RCC) in terms of pre-, peri- and postoperative outcome, complications and oncologic outcome. METHODS: We investigated 61 patients with evidence of RCC and an extended TT in the IVC undergoing radical nephrectomy and tumour thrombectomy at our tertiary referral centre. Patients and operative characteristics were recorded and complications were analysed using the Clavien-Dindo classification. Follow-up data were retrieved by contacting the treating outpatient urologists, general practitioners and patients. RESULTS: The TT level was II in 36, III in 8 and IV in 17 patients. Complications grade IIIb and higher according to the Clavien-Dindo classification occurred in nâ=â3 (8.4â%), nâ=â2 (25.0â%) and nâ=â5 (29.5â%) patients with level II, III and IV TT, respectively. The overall survival of patients with TT level II, III and IV at 24 months (60 months) was 66.9â% (41.6â%), 83.3â% (83.3â%) and 64.1â% (51.3â%). Presence of primary metastatic disease was the only significant independent predictor for OS.â CONCLUSIONS: Radical nephrectomy with tumour thrombectomy appears to be a feasible and effective treatment option in the management of patients with RCC and an extended IVC TT.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Thrombosis , Venous Thrombosis , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Nephrectomy/methods , Retrospective Studies , Thrombosis/complications , Thrombosis/surgery , Vena Cava, Inferior/surgery , Venous Thrombosis/complications , Venous Thrombosis/surgeryABSTRACT
To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité-Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65-69, Group 70-74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65-69, 88.9% and 76.2% for Group 70-74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65-69, 85.7% and 61.5% for Group 70-74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates.
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PURPOSE: Focal segmental glomerulosclerosis (FSGS) is a common cause for end-stage renal disease that can recur in the graft after kidney transplantation. The incidence of FSGS recurrence is reported in up to 47% of patients, predisposing those to possible poorer transplantation outcomes. Hence, we examined the incidence of FSGS recurrence and the effect on graft outcome in our patient cohort of living donor kidney transplantations (LDKT). PATIENTS AND METHODS: We analyzed 194 adult patients who received a LDKT between 2011 and 2017 of which 22 (11%) had FSGS as underlying disease. Demographic data and clinical outcomes, especially regarding recurrence of FSGS, were evaluated. RESULTS: FSGS recurrence was identified in three (14%) patients within three months after transplantation, of whom two patients (9%) lost their graft. There was no significant difference in graft survival comparing FSGS to other reasons for end-stage renal disease. CONCLUSION: Incidence of FSGS recurrence in the present patient cohort was within the range reported in the literature and comparatively low. Our data support LDKT as a treatment option in patients with end-stage renal disease due to FSGS.
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PURPOSE: To compare running suture (RS) and interrupted suture (IS) of vesicourethral anastomosis (VUA) during open retropubic radical prostatectomy (RRP) on early urinary continence and extravasation. PATIENTS AND METHODS: Single center analysis of 211 patients who underwent RRP performed by a single surgeon during 2008 to 2017 was retrospectively analyzed. For VUA, we used the standard interrupted suture technique (n=100) with a 3-0 PDS suture. The RS (n=111) was performed with 12-bite suture using 3-0 PDS. The primary endpoints were extravasation and early continence. Demographic and peri-operative data were collected and analyzed using Pearson's chi-square, t-Test and Mann-Whitney U-test. A binary logistic regression analysis was carried out to explore predictors that affected early continence after catheter removal. RESULTS: The rates of early urinary incontinence (UI) were 7.7% vs 42.2% (p<0.001). The duration of catheterization and hospitalization was significantly shorter in the interrupted group (4 days vs 5 days, p<0.001 and 5 days vs 6 days, p<0.001). The groups did not differ significantly in body mass index or prostate volume. There were older patients and higher PSA levels in the group with RS technique. No significant difference was found in the postoperative extravasation rates between both groups (13.5% vs 12%, p=0.742). CONCLUSION: Running vesicourethral anastomosis increased the rate of early urinary incontinence. Both anastomosis techniques provided a similar rate of postoperative urine extravasation. VUA should only be one of the many criteria that must be considered for the preservation of urinary continence of patients after RRP.
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As new biomarkers, circular RNAs (circRNAs) have been largely unexplored in prostate cancer (PCa). Using an integrative approach, we aimed to evaluate the potential of circRNAs and their linear transcripts (linRNAs) to act as (i) diagnostic biomarkers for differentiation between normal and tumor tissue and (ii) prognostic biomarkers for the prediction of biochemical recurrence (BCR) after radical prostatectomy. In a first step, eight circRNAs (circATXN10, circCRIM1, circCSNK1G3, circGUCY1A2, circLPP, circNEAT1, circRHOBTB3, and circSTIL) were identified as differentially expressed via a genome-wide circRNA-based microarray analysis of six PCa samples. Additional bioinformatics and literature data were applied for this selection process. In total, 115 malignant PCa and 79 adjacent normal tissue samples were examined using robust RT-qPCR assays specifically established for the circRNAs and their linear counterparts. Their diagnostic and prognostic potential was evaluated using receiver operating characteristic curves, Cox regressions, decision curve analyses, and C-statistic calculations of prognostic indices. The combination of circATXN10 and linSTIL showed a high discriminative ability between malignant and adjacent normal tissue PCa. The combination of linGUCY1A2, linNEAT1, and linSTIL proved to be the best predictive RNA-signature for BCR. The combination of this RNA signature with five established reference models based on only clinicopathological factors resulted in an improved predictive accuracy for BCR in these models. This is an encouraging study for PCa to evaluate circRNAs and their linRNAs in an integrative approach, and the results showed their clinical potential in combination with standard clinicopathological variables.
Subject(s)
Biomarkers, Tumor/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , RNA, Circular/genetics , Aged , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Oligonucleotide Array Sequence Analysis , Prognosis , Prostatectomy , Prostatic Neoplasms/surgery , RNA, Long Noncoding/genetics , ROC Curve , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Background: Circular RNAs (circRNAs) are a new class of RNAs with medical significance. Compared to that of linear mRNA transcripts, the stability of circRNAs against degradation owing to their circular structure is considered advantageous for their use as biomarkers. As systematic studies on the stability of circRNAs depending on the RNA integrity, determined as RNA integrity number (RIN), in clinical tissue samples are lacking, we have investigated this aspect in the present study under model and clinical conditions. Methods: Total RNA isolated from kidney cancer tissue and cell lines (A-498 and HEK-293) with different RIN after thermal degradation was used in model experiments. Further, RNA isolated from kidney cancer and prostate cancer tissue collected under routine surgical conditions, representing clinical samples with RIN ranging from 2 to 9, were examined. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis of several circRNAs (circEGLN3, circRHOBTB3, circCSNK1G3, circRNA4, and circRNA9), their corresponding linear counterparts, tissue-specific reference genes, and three microRNAs (as controls) was performed. The quantification cycles were converted into relative quantities and normalized to the expression of specific reference genes for the corresponding tissue. The effect of RIN on the expression of different RNA entities was determined using linear regression analysis, and clinical samples were classified into two groups based on RIN greater or lesser than 6. Results: The results of model experiments and clinical sample analyses showed that all relative circRNA expression gradually decreased with reduction in RIN values. The adverse effect of RIN was partially compensated after normalizing the data and limiting the samples to only those with RIN values > 6. Conclusions: Our results suggested that circRNAs are not stable in clinical tissue samples, but are subjected to degradative processes similar to mRNAs. This has not been investigated extensively in circRNA expression studies, and hence must be considered in future for obtaining reliable circRNA expression data. This can be achieved by applying the principles commonly used in mRNA expression studies.
Subject(s)
Biomarkers/metabolism , RNA, Circular/genetics , Cell Line , Cell Line, Tumor , Gene Expression Profiling/methods , HEK293 Cells , Humans , MicroRNAs/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain ReactionABSTRACT
INTRODUCTION: In living donor transplantation choosing the right donor and donor side for laparoscopic donor nephrectomy is a challenging task in clinical practice. Knowledge about anomalies in renal blood supply are crucial to evaluate the feasibility of the operative procedure. Few data so far exist whether the existence of a retroaortic left renal vein has an impact on living kidney transplantation outcome for donor and recipient. MATERIALS AND METHODS: We retrospectively analyzed 221 patients who underwent laparoscopic living donor nephrectomy between 2011 and 2017 for existence of a retroaortic left renal vein. Clinical characteristics and operative outcomes for donors and recipients were analyzed. RESULTS: 221 patients underwent donor nephrectomy between 2011 and 2017; 11 patients (4.98%) showed the feature of a retroaortic left renal vein, and in 8 patients (72.7%) out of those 11 the left kidney was chosen for transplantation. Mean preoperative serum creatinine was 0.77 (0.49-0.98) mg/dL and 1.28 (0.97-1.64) mg/dL at discharge. In recipients mean serum creatinine preoperatively, after 1 week, 1 month,1 year, 2 and 3 years of follow-up was 10.36 (6.09-20.77) mg/dL, 1.71 (0.67-2.72), 1.33 (0.70-1.89), 1.31 (0.95-2.13), 1.31 (0.98-2.13) and 1.33 (1.03-1.84), respectively. Neither donors nor recipients suffered from any operative complications. CONCLUSIONS: Laparoscopic living donor nephrectomy of a left kidney with retroaortic renal vein is safe for the donor, without limitation in the outcome for the recipient.
Subject(s)
Kidney Transplantation , Laparoscopy , Nephrectomy/methods , Renal Veins/abnormalities , Tissue and Organ Harvesting/methods , Adolescent , Adult , Aorta, Abdominal , Female , Humans , Living Donors , Male , Middle Aged , Retrospective Studies , Risk Factors , Young AdultABSTRACT
INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1â/pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014.âPre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews. RESULTS: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4â% of patients died during follow-up.â4.7â% and 8.4â% developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results. DISCUSSION: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local , Nephrectomy , Quality of Life , Retrospective Studies , Tertiary Care Centers , Treatment OutcomeABSTRACT
The aim of this study was 1) to evaluate and compare pre-, peri-, and post-operative data of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients undergoing native nephrectomy (NN) either before or after renal transplantation and 2) to identify advantages of optimal surgical timing, postoperative outcomes, and economical aspects in a tertiary transplant centre. This retrospective analysis included 121 patients divided into two groups-group 1: patients who underwent NN prior to receiving a kidney transplant (n = 89) and group 2: patients who underwent NN post-transplant (n = 32). Data analysis was performed according to demographic patient details, surgical indication, laboratory parameters, perioperative complications, underlying pathology, and associated mortality. There was no significant difference in patient demographics between the groups, however right-sided nephrectomy was performed predominantly within group 1. The main indication in both groups undergoing a nephrectomy was pain. Patients among group 2 had no postoperative kidney failure and a significantly shorter hospital stay. Higher rates of more severe complications were observed in group 1, even though this was not statistically significant. Even though the differences between both groups were substantial, the time of NN prior or post-transplant does not seem to affect short-term and long-term transplantation outcomes. Retroperitoneal NN remains a low risk treatment option in patients with symptomatic ADPKD and can be performed either pre- or post-kidney transplantation depending on patients' symptom severity.