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INTRODUCTION: Continent cutaneous urinary diversion (CCUD) post-cystectomy is an established approach addressing both oncological and functional indications. However, there is a noticeable gap of evidence when it comes to comparing outcomes between these indications, especially concerning the technique of Main Pouch I (MPI). This study aims to close the gap by analyzing the long-term functional and renal outcomes of patients with MPI after cystectomy due to both benign and malign bladder pathologies. METHODS: In this retrospective study, we examined 173 patients, who underwent MPI surgery between 2000 and 2022. Patients were categorized into a study group (benign conditions, n=26) and a control group (bladder cancer, n=52) using propensity-score matching. Clinical demographics, surgical outcomes, and functional/renal parameters were analyzed using unpaired t-tests and chi-square tests. RESULTS: Patients undergoing cystectomy with MPI due to benign bladder pathologies were significantly younger and had lower comorbidity burden compared to those with bladder cancer. In contrast to a significant higher incidence of chemotherapy in the oncological cohort, the long-term renal function was comparable between both populations. Surgical outcomes, revisions and postoperative complications did not differ significantly between both groups. Nearly 90% of patients in both groups showed full continence. CONCLUSION: This study demonstrates the efficacy and safety of MPI surgery in both benign and malignant conditions, proving favorable long-term renal and functional outcomes.
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Introduction Studies comparing refluxing versus non-refluxing ureteric implantation in continent cutaneous urinary diversion (CCUD) are scarce and often characterized by heterogeneous study populations. This work therefore aimed at comparing both techniques regarding long-term outcomes in a propensity-scored approach. Methods We identified n = 19 patients, totaling n = 38 renal units (RU), who underwent CCUD surgery at our hospital out of a pool of 120 patients. Of these 38 RU, 27 RU were implanted via refluxing ureteric implantation utilizing various procedures due to special intraoperative circumstances (short ureters, damage due to radiation). In terms of pre-operative renal function, a comorbidity index (ACCI), and gender, we compared them to n = 38 patients with a total of 76 RU with non-refluxing ureteric implantation in all RU (1:2 matching). The mean follow-up was 56 (IQR 23-112) months. Results Long-term renal function was comparable in CCUD patients receiving refluxing vs. non-refluxing ureteric implantation (eGFR 63,11 ml/min vs. 71,7 ml/min, p=0,22) with an average decline of 17,4 ml/min and 13,69 ml/min during the follow-up period, respectively. Also, the rate of new-onset CKD (both 15%, p=1), the need for alkalizing medication or number of pyelonephritis episodes did not significantly differ between the groups. In cox regression analysis, ACCI was the single most predictive parameter for the development of new-onset CKD (HR: 1.71 [1.10-2.66], p=0.0167). None of the RU in the refluxing group needed revisional surgery concerning the ureterointestinal anastomosis, whereas 7 RU of the non-refluxing group did. Conclusions Our study confirms that refluxing ureteric implantation in CCUDs is a valid and safe procedure regarding long-term renal, metabolic and functional outcomes. Our data also suggest that patients should be counselled according to their comorbidities regarding to long-term renal function.
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INTRODUCTION: Metformin (MF) intake could be associated with a favorable outcome in sunitinib (SUT)- and axitinib (AX)-treated clear cell renal cell carcinoma (ccRCC) patients. Functionally, MF induces miR-205, a microRNA serving as a tumor suppressor in several cancers. METHODS: Real-time quantitative PCR, viability assays, and Western blotting analyzed MF and SUT/AX effects in RCC4 and 786-O cells. A tetracycline-inducible overexpression model was used to study the role of miR-205 and its known target gene, VEGFA. We analyzed miR-205 and VEGFA within a public and an in-house ccRCC cohort. Human umbilical vein endothelial cell (HUVEC) sprouting assays examined miR-205 effects on angiogenesis initiation. To determine the influence of the von Hippel-Lindau tumor suppressor (VHL), we examined VHLwt reexpressing RCC4 and 786-O cells. RESULTS: Viability assays confirmed a sensitizing effect of MF toward SUT/AX in RCC4 and 786-O cells. Overexpression of miR-205 diminished VEGFA expression - as did treatment with MF. Tumor tissue displayed a downregulation of miR-205 and an upregulation of VEGFA. Accordingly, miR-205 caused less and shorter vessel sprouts in HUVEC assays. Finally, VHLwt-expressing RCC4 and 786-O cells displayed higher miR-205 and lower VEGFA levels. CONCLUSION: Our results support the protective role of MF in ccRCC and offer functional insights into the clinical synergism with tyrosine kinase inhibitors.
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Carcinoma de Células Renais , Neoplasias Renais , Metformina , MicroRNAs , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Metformina/farmacologia , Linhagem Celular Tumoral , MicroRNAs/genética , Sunitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Quantification of [68 Ga]-labeled PSMA PET predicts response in patients with prostate cancer (PC) who undergo PSMA-targeted radioligand therapy (RLT). Given the increasing use [18F]-labeled radiotracers, we aimed to determine whether the uptake derived from [18F]PSMA-1007 PET can also identify responders and to assess its prognostic value relative to established clinical parameters. METHODS: We retrospectively analyzed 103 patients with metastatic, castration-resistant PC who were treated with [177Lu]Lu-PSMA I&T. We calculated SUVmean, SUVmax, PSMA-avid tumor volume (TV), and total lesion PSMA (defined as PSMA-TV*SUVmean) on pre-therapeutic [18F]PSMA-1007 PET. Laboratory values for hemoglobin, C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alkaline phosphatase (AP) were also collected prior to RLT. We performed univariable Cox regression followed by multivariable and Kaplan-Meier analyses with overall survival (OS) serving as endpoint. Last, we also computed a risk factor (RF) model including all items reaching significance on multivariable analysis to determine whether an increasing number of RFs can improve risk stratification. RESULTS: A total of 48 patients died and median OS was 16 months. On univariable Cox regression, SUVmean, CRP, LDH, hemoglobin, and the presence of liver metastases were significantly associated with OS. On multivariable Cox regression, the following significant prognostic factors for OS were identified: SUVmean (per unit, HR, 0.91; P = 0.04), the presence of liver metastases (HR, 2.37; P = 0.03), CRP (per mg/dl, HR, 1.13; P = 0.003), and hemoglobin (per g/dl, HR, 0.76; P < 0.01). Kaplan-Meier analysis showed significant separation between patients with a SUVmean below or above a median SUVmean of 9.4 (9 vs 19 months, HR 0.57; P = 0.03). Of note, patients with only one RF (median OS not reached) showed longest survival compared to patients with two (11 months; HR 2.43 95% CI 1.07-5.49, P = 0.02) or more than two RFs (7 months; HR 3.37 95% CI 1.62-7.03, P < 0.001). CONCLUSION: A lower SUVmean derived from [18F]PSMA-1007, higher CRP, lower hemoglobin, and the presence of liver metastases are associated with reduced OS in patients undergoing RLT. An early RF model also demonstrated that an increasing number of those factors is linked to worse outcome, thereby emphasizing the importance of clinical and imaging parameters for adequate risk stratification.
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Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Antígeno Prostático Específico/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Dipeptídeos/uso terapêutico , Tomografia por Emissão de Pósitrons , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Lutécio/uso terapêuticoRESUMO
PURPOSE: Renal cysts comprise benign and malignant entities. Risk assessment profits from CT/MRI imaging using the Bosniak classification. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this deficit but warrants standardization. This study addresses the benefits of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts. METHODS: 247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classification were correlated with histopathological diagnosis. Interobserver agreement between the classifications was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented. RESULTS: 146 patients (156 lesions) were included. CEUS classified 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-Bosniak-III, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ = 0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant differences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type. CONCLUSION: The CEUS-Bosniak classification is an essential tool in clinical practice to differentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care.
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Cistos , Doenças Renais Císticas , Neoplasias Renais , Humanos , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste , Rim/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/patologia , Cistos/patologiaRESUMO
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS). MATERIALS AND METHODS: In this bicentric analysis, we included 184 mCRPC patients treated with 177 Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan-Meier curves and log-rank comparison. RESULTS: A total of 114/184 patients (62.0%) showed any PSA decline (PSA response >50%, 55/184 [29.9%]). For individuals exhibiting a PSA decline >50%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95% confidence interval [95% CI] = 0.44-0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95% CI = 0.25-0.60; p < 0.001). CONCLUSIONS: In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50%, RLT should be continued.
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Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Antígenos de Superfície , Dipeptídeos/uso terapêutico , Glutamato Carboxipeptidase II , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio/uso terapêutico , Masculino , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Sobreviventes , Resultado do TratamentoRESUMO
BACKGROUND: Radioligand therapy (RLT) with 177Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [177Lu]Lu-PSMA I&T RLT in a long-term follow-up. MATERIALS AND METHODS: Ninety-two mCRPC patients treated with [177Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (intervalDiagnosis-RLT, per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan-Meier analyses. RESULTS: Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02-1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01-1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06-1.26; P = 0.001), and intervalDiagnosis-RLT (HR, 0.95, 95% CI 0.91-0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and intervalDiagnosis-RLT, 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan-Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged intervalDiagnosis-RLT (P ≤ 0.01, respectively). CONCLUSION: In mCRPC patients treated with [177Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [177Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.
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Lutécio , Neoplasias de Próstata Resistentes à Castração , Aspartato Aminotransferases/uso terapêutico , Proteína C-Reativa , Dipeptídeos/uso terapêutico , Seguimentos , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lactato Desidrogenases , Ligantes , Lutécio/uso terapêutico , Masculino , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Ureia/análogos & derivadosRESUMO
INTRODUCTION: In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. MATERIALS AND METHODS: In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan-Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). RESULTS: Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22-0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30-0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78-2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38-4.05; P = 0.68). CONCLUSION: Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.
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Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Lutécio , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/patologia , Dipeptídeos/efeitos adversos , Biomarcadores Tumorais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. MATERIALS AND METHODS: A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [177Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [177Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. RESULTS: Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [177Lu]Lu-PSMA I&T and five (9.1%) for [177Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [177Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [177Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [177Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). CONCLUSION: In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.
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Neoplasias de Próstata Resistentes à Castração , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio/uso terapêutico , Masculino , Análise por Pareamento , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento , Ureia/análogos & derivados , Ureia/uso terapêuticoRESUMO
PURPOSE: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases. METHODS: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results. RESULTS: Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative. CONCLUSION: Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.
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Radioisótopos de Gálio , Neoplasias da Próstata , Ácido Edético , Humanos , Masculino , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia , Ureia/análogos & derivadosRESUMO
PURPOSE: To explore the usability and diagnostic accuracy for prostate cancer of three multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS)-guided fusion biopsy systems operated by the same urologists. METHODS: We performed a prospective, observational study including patients that underwent prostate biopsy due to a visible lesion in mpMRI (PI-RADS ≥ 3). We consecutively assessed two platforms with a rigid image registration (BioJet, D&K Technologies and UroNav, Invivo Corporation) and one with an elastic registration (Trinity, KOELIS). Four urologists evaluated each fusion system in terms of usability based on the System Usability Scale and diagnostic accuracy based on the detection of prostate cancer. RESULTS: We enrolled 60 consecutive patients that received mpMRI/TRUS-guided prostate biopsy with the BioJet (n = 20), UroNav (n = 20) or Trinity (n = 20) fusion system. Comparing the rigid with the elastic registration systems, the rigid registration systems were more user-friendly compared to the elastic registration systems (p = 0.012). Similarly, the prostate biopsy with the rigid registration systems had a shorter duration compared to the elastic registration system (p < 0.001). Overall, 40 cases of prostate cancer were detected. Of them, both the BioJet and UroNav fusion systems detected 13 prostate cancer cases, while the Trinity detected 14. No significant differences were demonstrated among the three fusion biopsy systems in terms of highest ISUP Grade Group (p > 0.99). CONCLUSIONS: Rigid fusion biopsy systems are easier to use and provide shorter operative time compared to elastic systems, while both types of platforms display similar detection rates for prostate cancer. Still, further high-quality, long-term results are mandatory.
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Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto , Reprodutibilidade dos Testes , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Complex soft tissue defects involving the lower abdomen, perineum, and groin (LAPG) represent reconstructive challenges following urologic surgery. Consequently, these often require an interdisciplinary approach involving plastic surgery. While pedicled flaps from the lower abdomen are a reliable option, previous placement of colostomies and urinary urostomies renders these flap types unavailable. Here, the pedicled anterolateral thigh perforator (ALT) flap represents a reliable pedicled alternative which can harvest from the thigh. MATERIALS AND METHODS: A retrospective data analysis of pedicled perforator flaps harvested from the thigh to reconstruct soft tissue defects was conducted. Seven patients treated in the urology department with soft tissue defects following tumor resection, infection, and dehiscence were included. RESULTS: In all patients, the ALT flap was utilized successfully to reconstruct soft tissue defects up to 450 cm2 in size. All flaps survived. In 1 case, prolonged wound healing was observed. All defects were adequately addressed with no recurrence of dehiscence or fistula formation. CONCLUSIONS: Pedicled perforator flaps represent a valid option for the soft tissue reconstruction of the lower abdomen and perineum when a pedicled rectus abdominis flap is no longer available. This flap is, therefore, a good option in an interdisciplinary approach to soft tissue reconstruction, especially following urologic surgery, which is predominantly performed in the LAPG region.
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Abdome/cirurgia , Virilha/cirurgia , Retalho Perfurante , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Urológicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coxa da Perna/cirurgiaRESUMO
PURPOSE: The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment. METHODS: A total of 82 men were included in the study and were imaged with 68Ga-PSMA I&T PET/CT to assess the distribution of PSMA-avid disease for staging purposes (11 with low-risk, 32 with intermediate-risk, and 39 with high-risk PCa). Forty patients (20 with intermediate- and 20 with high-risk disease) underwent subsequent radical prostatectomy with extended pelvic lymph node dissection which allowed for correlation of imaging findings with histopathologic data. RESULTS: PSMA-positive disease was detected in 83% of patients with 66/82 (80.5%) primary tumours being visualized. PSMA-avid lymph nodes were recorded in 17/82 patients (20.7%, 3 with intermediate-risk and 14 with high-risk PCa); distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p < 0.001) and Gleason scores (GSC; r = 0.35, p = 0.001), respectively. In correlation with histopathology, calculated per-region sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of lymph node metastases were 35.0%, 98.4%, 63.6%, 95.0%, and 93.0%, respectively. CONCLUSIONS: In patients with initial diagnosis of intermediate- and high-risk prostate cancer, 68Ga-PSMA I&T PET/CT emerges as a relevant staging procedure by identifying nodal and/or distant metastases. Due to the low prevalence of extraprostatic disease, its value seems to be limited in low-risk disease.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Estadiamento de Neoplasias , Oligopeptídeos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. METHODS: Study design: "RACE IT" (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11-15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. DISCUSSION: This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. TRIAL REGISTRATION: Protocol Code RACE IT: AB 65/18; EudraCT: 2018-001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018.
Assuntos
Radioterapia Adjuvante , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Cistectomia , Feminino , Humanos , Imunoterapia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Resultado do TratamentoRESUMO
PURPOSE: We evaluated the role of magnetic resonance imaging of the penis in the diagnosis of penile fracture and/or concomitant urethral lesions in real-life emergency settings compared with intraoperative findings. MATERIALS AND METHODS: A total of 43 patients presented with suspicion of penile fracture between January 2006 and December 2016. Magnetic resonance imaging was performed in 28 patients prior to surgical treatment in the emergency setting. Surgery was done in all patients via a subcoronal, circumferential degloving approach. We calculated sensitivity, specificity, and positive and negative predictive values as well as likelihood ratios of the positive and negative results of the agreement between magnetic resonance imaging and intraoperative findings. RESULTS: Intraoperatively penile fracture was confirmed in 19 of 28 patients (67.9%) and a concomitant urethral lesion was observed in 5 of 28 (17.9%). Magnetic resonance imaging findings were highly associated with intraoperative findings of tunical rupture, including 100% sensitivity (95% CI 98.5-100), 77.8% specificity (95% CI 50.6-100), 90.5% positive predictive value (95% CI 78-100), 100% negative predictive value (95% CI 97.6-100) and a positive result likelihood ratio of 4.5. Magnetic resonance imaging had lower accuracy for urethral lesions with 60% sensitivity (95% CI 17.1-100), 78.3% specificity (95% CI 61.5-95.1), 37.5% positive predictive value (95% CI 4-71), 90% negative predictive value (95% CI 76.9-100) and a positive result likelihood ratio of 2.76. CONCLUSIONS: Magnetic resonance imaging may be applicable in the emergency setting if the goal is to treat all men who warrant intervention. It has high sensitivity and negative predictive value for tunical rupture and concomitant urethral lesions. Therefore, it could help avoid unnecessary surgery by excluding the diagnosis. However, solitary magnetic resonance imaging is not sufficient for diagnosis and it should not replace clinical assessment or delay surgical exploration.
Assuntos
Imageamento por Ressonância Magnética , Pênis/lesões , Ruptura/diagnóstico por imagem , Uretra/lesões , Adulto , Idoso , Emergências , Humanos , Masculino , Pessoa de Meia-Idade , Pênis/diagnóstico por imagem , Pênis/cirurgia , Valor Preditivo dos Testes , Ruptura/cirurgia , Sensibilidade e Especificidade , Uretra/diagnóstico por imagem , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
PURPOSE: The study aimed to evaluate the impact of the validated functional dexterity test and the Mini-Mental Status test on subjective functional outcomes, medical care situation, and health-related quality of life (HRQoL) after urinary diversion (UD). PATIENTS AND METHODS: A total of 106 patients (n = 26 ileal conduits, n = 29 neobladders, and n = 51 ileocecal pouches) were included in this combined retrospective (n = 77) and prospective (n = 29) observational study. All patients performed the 2 tests mentioned above and filled out self-designed questionnaires with diversion and HRQoL items. In the prospective cohort, the tests were performed preoperatively and the questionnaires were filled out preoperatively as well as 3 and 6 months after surgery. RESULTS: Reduced dexterity and cognitive skills were significantly associated with increased patient age and subjective constraints in stoma care of ileal conduits, self-catheterization in ileocecal pouches, and continence in neobladders. Overall HRQoL, however, was not affected by dexterity or cognitive measures. CONCLUSIONS: Assessing the cognitive status and functional dexterity of patients undergoing UD might provide a useful objective clinical tool to aid in decision-making regarding the type of UD and postoperative medical care situation. Further prospective data are needed to confirm these findings and further simplify the methods used here.
Assuntos
Tomada de Decisão Clínica , Cognição , Lateralidade Funcional , Testes Neuropsicológicos , Qualidade de Vida , Derivação Urinária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Saúde Mental , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Autocuidado , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Derivação Urinária/efeitos adversos , Adulto JovemRESUMO
PURPOSE: Renal cell carcinoma (RCC) forming tumor thrombus (TT) of vena cava (VC) is characterized by poor prognosis. Nevertheless, the outcome of patients after radical surgery varies. To date only limited data concerning prognostic biomarkers in this RCC subgroup are available. METHODS: Out of 159 patients with pT3b/c RCC, 95 patients without synchronous distant metastases at time of diagnosis were included in the study cohort. After immunohistochemical (IHC) evaluation of E-cadherin and ß-Catenin expression, association with clinical, histopathological and survival was assessed by univariate analysis, multivariate analysis, and Kaplan-Meier-analysis. Cancer-specific survival (CSS) rates and overall survival (OS) rates were estimated using Kaplan-Meier analysis and compared using Log rank test. RESULTS: We found a significant correlation between E-cadherin overexpression and initial lymph node metastasis (ρ = 0.300, p = 0.003), positive surgical margins (ρ = 0.210, p = 0.043), and the development of distant metastases (ρ = 0.258, p = 0.012). Furthermore, we observed a significant correlation of ß-Catenin overexpression with higher tumor stage pT3c (ρ = 0.230, p = 0.028) and initial lymph node metastases (ρ = 0.236, p = 0.025). Survival analysis revealed a statistically significant association of both E-cadherin and ß-Catenin overexpression with worse CSS (p < 0.001 and p = 0.007, respectively) and OS (p < 0.001 and p = 0.041, respectively). Multivariate analysis revealed initial lymph node metastasis as the only predictive factor for worse OS (HR 4.54, 95% CI 2.30-8.93; p < 0.001). E-Cadherin and ß-Catenin expression failed to be significant in multivariable analysis for OS and CSS. CONCLUSIONS: In a large series of RCC with TT of VC high IHC expression of E-cadherin and ß-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS. This might help to identify patients at risk for recurrence who might benefit from adjuvant therapy or stricter follow-up.
Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Trombose/diagnóstico , beta Catenina/metabolismo , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prognóstico , Risco , Trombose/patologia , Resultado do Tratamento , Veia Cava Inferior/patologiaRESUMO
The established biomarkers of Alzheimer's disease (AD) require invasive endeavours or presuppose sophisticated technical equipment. Consequently, new biomarkers are needed. Here, we report that plasma levels of soluble amyloid precursor protein ß (sAPPß), a protein of the initial phase of the amyloid cascade, were significantly lower in patients with symptomatic AD (21 with mild cognitive impairment due to AD and 44 with AD dementia) with AD-typical cerebral hypometabolic pattern compared with 27 cognitively healthy elderly individuals without preclinical AD. These findings yield further evidence for the potential of sAPPß in plasma as an AD biomarker candidate.
Assuntos
Doença de Alzheimer/sangue , Precursor de Proteína beta-Amiloide/sangue , Disfunção Cognitiva/sangue , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Saphenous vein graft (SVG) aneurysms (SVGA) after renal transplantation represents a rare vascular complication with subsequent challenging multidisciplinary treatment. We present a case of a 30-year-old female who received a live donor kidney transplantation for end-stage renal disease that was caused due to the hemolytic uremic syndrome. Postoperatively, an insufficient graft perfusion due to an arterial kinking was noted and repaired using an autologous SVG interposition. Ten years later, a 3-cm aneurysm of the SVG at the anastomotic site with the common iliac artery was discovered. Multidisciplinary surgical exploration with excision of the aneurysm-carrying vein graft and interposition of a new autologous SVG was successfully carried out with preservation of renal allograft's function. Treatment of SVGA after rental transplantation with a new autologous SVG is challenging but feasible, requiring a multidisciplinary approach in order to guarantee successful rates and to prevent allograft loss.
Assuntos
Aneurisma/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores Vivos , Artéria Renal/cirurgia , Veia Safena/transplante , Enxerto Vascular/métodos , Adulto , Aneurisma/diagnóstico por imagem , Aneurisma/etiologia , Biópsia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Transplante de Rim/efeitos adversos , Angiografia por Ressonância Magnética , Veia Safena/diagnóstico por imagem , Veia Safena/patologia , Transplante Autólogo , Resultado do Tratamento , Enxerto Vascular/efeitos adversosRESUMO
BACKGROUND: The impact of local tumor ablative therapy in oligometastasized prostate cancer (PC) is still under debate. To gain data for this approach, we evaluated oligometastasized PC patients receiving stereotactic body radiotherapy (SBRT) to bone metastases. METHODS: In this retrospective study, 15 oligometastasized PC patients with a total of 20 bone metastases were evaluated regarding biochemical progression-free survival (PSA-PFS), time to initiation of ADT, and local control rate (LCR). Three patients received concomitant androgen deprivation therapy (ADT). RESULTS: The median follow-up after RT was 22.5 months (range 7.0-53.7 months). The median PSA-PFS was 6.9 months (range 1.1-28.4 months). All patients showing a decrease of PSA level after RT of at least factor 10 reveal a PSA-PFS of >12 months. Median PSA-PFS of this sub-group was 23.1 months (range 12.1-28.4 months). Local PFS (LPFS) after 2 years was 100%. One patient developed a local failure after 28.4 months. Median distant PFS (DPFS) was 7.36 months (range 1.74-54.34 months). The time to initiation of ADT in patients treated without ADT was 9.3 months (range 2.6-36.1 months). In all patients, the time to intensification of systemic therapy or the time to initiation of ADT increased from 9.3 to 12.3 months (range 2.6-36.1 months). Gleason-Score, ADT or the localization of metastasis had no impact on PFS or time to intensification of systemic therapy. No SBRT related acute or late toxicities were observed. CONCLUSION: Our study shows that SBRT of bone metastases is a highly effective therapy with an excellent risk-benefit profile. However, PFS was limited due to a high distant failure rate implying the difficulty for patient selection for this oligometastatic concept. SBRT offers high local cancer control rates in bone oligometastases of PC and should be evaluated with the aim of curation or to delay modification of systemic treatment.