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1.
World J Urol ; 42(1): 239, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630278

RESUMO

PURPOSE: An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult. METHODS: The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up. RESULTS: Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4). CONCLUSION: The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.


Assuntos
Transplante de Rim , Procedimentos de Cirurgia Plástica , Cirurgiões , Derivação Urinária , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto
3.
World J Urol ; 42(1): 161, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488940

RESUMO

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.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Artéria Renal/cirurgia , Doadores Vivos , Estudos Retrospectivos , Sobrevivência de Enxerto , Rim/diagnóstico por imagem , Rim/cirurgia , Rim/irrigação sanguínea , Resultado do Tratamento
4.
World J Urol ; 42(1): 120, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446250

RESUMO

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.


Assuntos
Rim , Nefrectomia , Humanos , Estudos Retrospectivos , Nefrectomia/efeitos adversos , Transplante Homólogo , Sobrevivência de Enxerto
5.
Urologie ; 63(4): 361-366, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38378943

RESUMO

BACKGROUND: The first robot-assisted kidney transplantation (RAKT) was conducted in 2010, and the first time in Germany in 2016. As more than 5 years have passed, current evidence, technological developments and the latest (German) experience are presented. OBJECTIVES: The current evidence and experience of RAKT was investigated from an international and German perspective. MATERIALS AND METHODS: In a systemic search, relevant publications were analyzed and compared with the experiences at a German urological transplant department. RESULTS: From an international perspective, RAKT can now be considered a standard procedure at experienced departments, as more than 680 RAKT have been documented in Europe. The functional results are excellent with low complication rates and good mid- to long-term functional outcomes. Although RAKT was initially only performed with living organ donations, it has also been successfully conducted with cadaveric grafts. The surgical technique can be applied in challenging and complex situations, such as for arteriosclerotic recipient vessels or for kidney transplantations in children. Although RAKT is still not widely performed in Germany, the university hospital in Marburg, the third urological department in Germany, has successfully initiated a robotic transplant program. CONCLUSIONS: Compared to open kidney transplantation, robot-assisted kidney transplantation enables at least noninferior results. It further appears to translate the well-documented advantages of minimally invasive surgery to kidney transplantation. However, its spread throughout Germany is only slowly increasing, possibly because only a handful of urological departments still perform kidney transplantations.


Assuntos
Transplante de Rim , Procedimentos Cirúrgicos Robóticos , Robótica , Criança , Humanos , Transplante de Rim/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Europa (Continente) , Alemanha
6.
World J Urol ; 42(1): 85, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363345

RESUMO

PURPOSE: The Eurotransplant Senior program allocating grafts from donors ≥ 65 years to recipients aged ≥ 65 years has proven good results within the last 20 years. However, "old" grafts are also allocated to younger recipients < 65 years, and this outcome of "old for young" kidney transplantations (KT) still lacks detailed investigations. METHODS: All "old for young" KT performed at four tertiary referral centers were retrospectively compared including a recent follow-up, stratifying for "old for young" (donor ≥ 65 years to recipient < 65 years) vs. "very old for young" KT (donor ≥ 70 years to recipient < 65 years). RESULTS: Overall, 99 patients were included with 56 (56.6%) "old for young" and 43 (43.4%) "very old for young" KT. The median waiting time did not differ (60.7 vs. 45.8 months, respectively) at comparable living donation rates (57.1% vs. 44.2%) as well as intra- and postoperative results. At a median follow-up of 44 months (range 1; 133), the 3-year graft survival of 91% vs. 87% did not significantly vary. In subgroup analyses assessing living donation or donation after brain death (DBD) KT only, the graft survival was significantly longer for "old for young" KT within the living donation subgroup. In multivariate Cox regression analyses, the presence of panel-reactive antibodies was the only significant impact factor on graft survival (HR 8.32, p = 0.001). CONCLUSION: This analysis clearly demonstrates the effectiveness of the "old for young" approach, enabling favorable perioperative results as well as comparable data of graft- and overall survival, while reducing waiting time for eligible patients.


Assuntos
Transplante de Rim , Humanos , Estudos Retrospectivos , Listas de Espera , Doadores de Tecidos , Sobrevivência de Enxerto
7.
J Clin Med ; 12(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38002699

RESUMO

PURPOSE: To determine oncological and functional outcomes and side effects after focal therapy of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU). METHODS: This retrospective single-center study included 57 consecutive patients with localised PCa. Aged 18-80 with ≤2 suspicious lesions on mpMRI (PIRADS ≥ 3), PSA of ≤15 ng/mL, and an ISUP GG of ≤2. HIFU was performed between November 2014 and September 2018. All men had an MRI/US fusion-guided targeted biopsy (TB) combined with a TRUS-guided 10-core systematic biopsy (SB) prior to focal therapy. HIFU treatment was performed as focal, partial, or hemiablative, depending on the prior histopathology. Follow-up included Questionnaires (IIEF-5, ICIQ, and IPSS), prostate-specific antigen (PSA) measurement, follow-up mpMRI, and follow-up biopsies. RESULTS: The median age of the cohort was 72 years (IQR 64-76), and the median PSA value before HIFU was 7.3 ng/mL (IQR 5.75-10.39 ng/mL). The median follow-up was 27.5 (IQR 23-41) months. At the time of the follow-up, the median PSA value was 2.5 ng/mL (IQR 0.94-4.96 ng/mL), which shows a significant decrease (p < 0.001). In 17 (29.8%) men, mpMRI revealed a suspicious lesion, and 19 (33.3%) men had a positive biopsy result. Only IIEF values significantly decreased from 16 (IQR 10.75-20.25) to 11.5 (IQR 4.5-17) (p < 0.001). The rate of post-HIFU complications was low, at 19.3% (11 patients). The limitation of this study is the lack of long-term follow-up. CONCLUSIONS: HIFU as a therapy option for nonmetastatic, significant prostate cancer is effective in the short term for carefully selected patients and shows a low risk of adverse events and side effects.

8.
J Clin Invest ; 133(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37815874

RESUMO

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , Memória Imunológica , COVID-19/prevenção & controle , Tecido Linfoide , Vacinação , RNA Mensageiro , Anticorpos Antivirais
9.
Urol Oncol ; 41(12): 484.e17-484.e26, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37407421

RESUMO

INTRODUCTION AND OBJECTIVE: BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, and CancerCheck® UBC® rapid VISUAL are urinary-based rapid tests. This multicenter study is the first study comparing all available rapid tests on a large cohort of bladder cancer patients and healthy controls in one setting. METHODS: In total 732 urine samples (second morning urine) in a real-world assessment have been analyzed. We evaluated clinical samples from 464 patients with histologically confirmed urothelial tumors of the urinary bladder (17 solitary CIS, 189 low-grade, 187 high-grade nonmuscle invasive, 71 high-grade muscle invasive), 77 patients with No Evidence of Disease (NED), and from 191 healthy controls. Urine samples were analyzed by the BTA stat®, NMP22® BladderChek®, UBC® Rapid Test point-of-care (POC) system using the concile Omega 100 POC reader, and CancerCheck® UBC® rapid VISUAL. Sensitivities and specificities were calculated by contingency analyses. RESULTS: All investigated urinary markers detected more pathological concentrations in urine of bladder cancer patients compared to tumor-free patients. The calculated diagnostic sensitivities for BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, CancerCheck® UBC® rapid VISUAL, and cytology were 62.4%, 13.4%, 58.2%, 28.6%, 36.2% for low-grade, 83.4%, 49.5%, 84.5%, 63.1%, 71.2% for high-grade nonmuscle invasive, and 95.8%, 35.2%, 76.1%, 50.7%, 67.7% for high-grade muscle-invasive bladder cancer. The specificity was 67.9%, 95.5%, 79.4%, 94.4%, and 83.7%, respectively. The area under the curve (AUC) after receiver operating characteristics (ROC) analysis for high-grade non-muscle-invasive tumors was 0.757, 0.725, 0.819, 0.787, and 0.774, respectively. CONCLUSIONS: The analysis of more than 700 urine samples offers an objective view on urine-based rapid diagnostics. Elevated pathological concentrations of markers in urine of bladder cancer patients were detected in all investigated tests. The highest sensitivities for high-grade non-muscle-invasive tumors were calculated for BTA stat® and UBC® Rapid Test, whereas NMP22® BladderChek®, and cytology showed the highest specificities. BTA stat® and UBC® Rapid Test have the potential to be used as a clinical valuable urinary protein biomarker for the detection of high-grade non-muscle-invasive bladder cancer patients and could be included in the management of these tumors.


Assuntos
Biomarcadores Tumorais , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/urina , Neoplasias da Bexiga Urinária/patologia , Proteínas Nucleares/urina , Sensibilidade e Especificidade
10.
J Clin Med ; 12(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37176757

RESUMO

Ureteral complications such as urinary leak, ureteral necrosis or ureteral stenosis are common complications after renal transplantation with major short- and long-term issues, including graft impairment and graft loss. At present, there is no agreement on the optimal management of ureteral complications. The aim of the current study was to evaluate the safety and efficacy of the self-expanding, large-caliber Allium ureteral stent in patients with ureteral complications following renal transplantation. In this retrospective study, the electronic database of Charité University Hospital was screened for patients receiving the self-expandable Allium ureteral stent in the transplant ureter after kidney transplantation between January 2016 and March 2022. Descriptive statistics were used to describe the outcomes. There were six men and four women with a median age of 61 years (interquartile range, 55 to 68 years). Nine out of 10 patients had ureteric stenosis, which was diagnosed at a median of two years (interquartile range 10 months to 9 years) following renal transplantation. The median operating time was 49 min (interquartile range, 30 to 60 min). Endoscopic Allium stent placement was successful in all patients with ureteric stenosis. The median length of stay in the hospital was four days (interquartile range 2 to 7 days). Only one patient (#5) had a postoperative grade IIIb Clavien-Dindo complication. Patients had follow-ups every 3 months with ultrasound and serum creatinine. Dislocation of the Allium stent was seen in four patients; all occurred within three months. Ultimately, three patients required ureteric re-implantation, two of which had early dislocation of the stent. Six patients are managed with a permanent Allium stent. The median dwell time was 11 months (interquartile range 3 to 20 months) and maximum dwell time was 23 months. The overall success rate was 60% (6 out of 10). According to our data, the Allium stent represents a safe and minimally invasive option with a success rate of 60%. It might, therefore, represent an alternative to DJ stents, nephrostomies or immediate re-implantation. As all dislocations occurred within three months, frequent early postoperative follow-up is required.

12.
Nephrol Dial Transplant ; 38(8): 1857-1866, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-36477607

RESUMO

BACKGROUND: High numbers of unknown classifications and inconsistent methodologies in previous studies make the interpretation of causes leading to graft loss difficult. In addition, data on a holistic view looking at both death with a functioning graft (DWFG) and death-censored graft failure (DCGF) are sparse. METHODS: In this single-centre study we included 1477 adult kidney transplants performed between 1997 and 2017, of which all 286 DWFGs until the end of observation were analysed and causes for death assigned. Additionally, the results were compared with the causes of 303 DCGFs of the same cohort to evaluate the impact of causes for overall graft loss. RESULTS: The most frequent causes for DWFG were cardiovascular disease (CVD) in 30.8%, malignancy in 28.3% and infections in 21%. Only 9.4% of reasons for DWFG were unknown. Sudden death occurred in 40% (35/88) of patients classified as DWFG due to CVD. Overall graft loss was related to the effect of immunosuppression in 36.2% [infection 20.9% (123/589), malignancy 15.3% (90/589)] and CVD in 22.4% (132/589). In 27.4% (161/589), graft failure was associated with underimmunosuppression (rejection). For infections (60 DWFG, 63 DCGF) and CVD (88 DWFG, 44 DCGF), a considerable overlap was observed between DWFG and DCGF. For patients >70 years of age at transplantation, medical events accounted for 78% of overall graft losses and only 6.5% were associated with rejection. CONCLUSIONS: DWFG and DCGF share more causes for graft loss than previously reported and sudden death plays an underestimated role in death with a functioning graft.


Assuntos
Doenças Cardiovasculares , Transplante de Rim , Adulto , Humanos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Terapia de Imunossupressão , Transplante de Rim/efeitos adversos
13.
Aktuelle Urol ; 54(1): 24-29, 2023 02.
Artigo em Alemão | MEDLINE | ID: mdl-36096141

RESUMO

BACKGROUND: Holmium Laser Enucleation of the Prostate (HoLEP) was established 20 years ago as an alternative to Transurethral Resection of the Prostate (TUR-P) based on improved morbidity in patients with benign prostate syndrome (BPS). HoLEP can be applied independently to almost all sizes of prostate glands and is recommended in national and international guidelines. Although the HoLEP procedure has a good reputation, many patients still prefer conservative treatment due to fears of side-effects such as pain and urinary incontinence. The aim of this study was to identify patients' feelings, fears and perception of their HoLEP treatment based on Patient-reported Outcome Measures (PROMs) via questionnaires. MATERIAL UND METHODS: During the time period from June to December 2020, 152 consecutive patients were treated by HoLEP due to BPS and were interviewed based on questionnaires right after their surgical treatment and 3 months later concerning their satisfaction as well as micturition and continence. Based on a written informed consent, 112 patients were included in the study, and a complete 3-month follow-up was available for 88 patients. RESULTS: The mean volume of enucleated prostate tissue was 62.1 [g] and the mean prostate volume estimated pre-operatively (trans-rectal ultrasound) was 83.1 [cm3]. Overall patient-reported satisfaction with the hospital stay including surgical treatment was 94.6%; after 3 months it was 91.8%. Concerning micturition, 76.5% of the patients reported satisfaction after surgery and 80.4% were satisfied after 3 months. Urinary incontinence was reported in 8.3% initially and in 9.1% after 3 months. Positive answers to questions concerning the quality of life index [L] were obtained in 62.1% initially and their number increased to 85.7% after 3 months. The share of negative answers decreased from 11.7% after surgery to 3.4% within the 3-month follow-up. DISCUSSION: HoLEP is a well-established treatment of BPS with lower side-effects compared with TUR-P according to the literature. To address doubts and misgivings, it is important to perform surveys on subjective patient satisfaction after the surgical procedure and over time. The high patient satisfaction could help future patients and the urologists treating them to establish the indication for HoLEP treatment earlier in order to avoid severe LUTS or catheterization.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Incontinência Urinária , Masculino , Humanos , Próstata/cirurgia , Ressecção Transuretral da Próstata/métodos , Hólmio , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Lasers de Estado Sólido/uso terapêutico , Resultado do Tratamento , Terapia a Laser/métodos , Incontinência Urinária/cirurgia , Estudos Retrospectivos
14.
Transpl Int ; 35: 10677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992746

RESUMO

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12-18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 ("Comirnaty"; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults.


Assuntos
COVID-19 , Transplante de Rim , Adolescente , Adulto , Anticorpos Antivirais , Vacina BNT162/administração & dosagem , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Humanos , Imunidade Humoral , Transplante de Rim/efeitos adversos , RNA Viral , SARS-CoV-2 , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
15.
Sci Rep ; 12(1): 13603, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948575

RESUMO

Magnetic resonance imaging/Ultrasound (MRI/US) fusion targeted biopsy (TB) in combination with a systematic biopsy (SB) improves cancer detection but limited data is available how to manage patients with a Prostate Imaging-Reporting and Data System (PI-RADS) ≥ 4 lesion and a negative biopsy. We evaluate the real-world management and the rate of clinically significant Prostate Cancer (csPCa) during follow-up. 1546 patients with a multi-parametric MRI (mpMRI) and a PI-RADS ≥ 3 who underwent SB and TB between January 2012 and May 2017 were retrospectively analyzed. 222 men with a PI-RADS ≥ 4 and a negative biopsy were included until 2019. For 177/222 (80%) complete follow-up data was obtained. 66/84 (78%) had an initial PI-RADS 4 and 18 (22%) a PI-RADS 5 lesion. 48% (84/177) received a repeat mpMRI; in the follow-up mpMRI, 39/84 (46%) lesions were downgraded to PI-RADS 2 and 11 (13%) to PI-RADS 3; three cases were upgraded and 28 lesions remained consistent. 18% (32/177) men underwent repeated TB and csPCa was detected in 44% (14/32). Our study presents real world data on the management of men with a negative TB biopsy. Men with a positive mpMRI and lesions with high suspicion (PI-RADS4/5) and a negative targeted biopsy should be critically reviewed and considered for repeat biopsy or strict surveillance. The optimal clinical risk assessment remains to be further evaluated.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Seguimentos , Humanos , Biópsia Guiada por Imagem , Masculino , Neoplasias da Próstata/patologia , Estudos Retrospectivos
16.
Int J Mol Sci ; 23(14)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35887247

RESUMO

Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome­rate of ypT0 status­to justify subsequent prospective validation within the "BladderBRIDGister". Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal−Wallis, Mann−Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Músculos/metabolismo , Terapia Neoadjuvante/efeitos adversos , Invasividade Neoplásica , RNA Mensageiro , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
17.
Clin Hemorheol Microcirc ; 82(1): 75-83, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662110

RESUMO

BACKGROUND: B-Mode and Doppler ultrasound are standard diagnostic techniques for early postoperative monitoring and long-term follow-up of kidney transplants. In certain cases, contrast-enhanced ultrasound (CEUS) is used to clarify unclear Doppler findings. OBJECTIVE: To investigate the diagnostic performance of CEUS in the workup of renal allograft pathologies. METHODS: A systematic search for CEUS examinations of renal transplants conducted in our department between 2008 and 2020 was performed using the following inclusion criteria: i) patient age ≥18 years and ii) confirmation of diagnosis by biopsy and histopathology, imaging follow-up by CEUS, contrast-enhanced computed tomography (ceCT), contrast-enhanced magnetic resonance imaging (ceMRI), or angiography, or intraoperative findings. Exclusion criteria were: i) CEUS performed in the setting of a study and ii) CEUS for other indications than dedicated renal transplant examination. Statistical analysis was performed separately for subgroups with different indications (focal vs non-focal). RESULTS: Overall, 78 patients were included in the statistical analysis, which revealed high sensitivity (92.2%, 95% -confidence interval [CI] 81.5-96.9%) and high specificity (88.9%, 95% -CI 71.9-96.1%) of CEUS. CONCLUSIONS: The high diagnostic performance demonstrated here and the superficial location of kidney allografts advocate the additional use of CEUS in the follow-up of renal transplant recipients.


Assuntos
Meios de Contraste , Transplante de Rim , Adolescente , Aloenxertos/diagnóstico por imagem , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Transplante de Rim/métodos , Centros de Atenção Terciária , Ultrassonografia/métodos
18.
Front Surg ; 9: 881494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586502

RESUMO

Introduction: Frameshift in medical management as well as in surgical thinking is putting the patient as a whole is the focus, rather than just the disease. To optimize the treatment of our pediatric transplant patients in our institution, we changed in 2013 the transplant program setting, treating, and operating all patients with pediatric transplant exclusively in a pediatric environment. The aim of this study was to analyze whether or not this change had an impact on patients safety, patient population, and patients and transplant outcome. Methods: In the retrospective analysis, we compared transplant outcome of two eras. Era1 (2008-2012) solely included patients treated in the adult facilities, era 2 (2013-2017) patients were exclusively treated in the pediatric environment. Results: There were 53 patients with renal transplant, with era 1 (28 patients) and era 2 (25 patients). Overall mortality was 5.6%. Median recipient age at transplantation was 13.2 years in era 1 and 8.59 years in era 2, median recipient weight at transplantation was 41.7 kg in era 1 vs. 26 kg in era 2, median size 149. 5 cm (era 1) vs. 123 cm in era2 (p = 0.05). The direct recipient/donor weight ratio remained stable in both eras, for recipients below 20 kg we saw a larger weight mismatch in era 1 (0.84 vs. 0.66). In the subgroup of patients with congenital anomalies of the kidney and urinary tract (CAKUT) those were significantly younger at onset of dialysis (p < 0.001) and at time of transplantation (p < 0.001), also they were less in body weight (p < 0.01), and body size (p < 0.001), this subgroup was larger in era 2. HLA mismatch data, serum creatinine, and GFR yield comparable results in both groups. Median time to detection of DSA was 46.2 month (3.8 years). Conclusion: Since children with ESRD at the time of transplant trend to be younger and smaller, it is crucial to ensure a medical environment that is able to address their particular challenges. Even in this recipient cohort, renal transplantation can be performed safely as outlined by our data.

19.
J Clin Med ; 11(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35330022

RESUMO

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.

20.
J Clin Med ; 11(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35160243

RESUMO

Contrast-enhanced ultrasound (CEUS) is a widely used diagnostic tool for analyzing perfusion and characterizing lesions in several organs. However, to date, it has not been sufficiently investigated whether there is an association between CEUS findings and kidney function. This study aimed at identifying the potential relationship between kidney function and the renal perfusion status determined by CEUS in living kidney donors. A total of 30 living kidney donors examined between April 2018 and March 2020 were included in the study. All patients underwent various diagnostic procedures for evaluation of renal function. CEUS was performed in all 30 donors one day before nephrectomy. Kidney perfusion was quantified using a postprocessing tool (VueBox, Bracco Imaging). Various perfusion parameters were subsequently analyzed and compared with the results of the other methods used to evaluate kidney function. Of all parameters, mean signal intensity (MeanLin) had the strongest correlation, showing significant correlations with eGFR (CG) (r = -0.345; p = 0.007) and total kidney volume (r = -0.409; p = 0.001). While there was no significant correlation between any perfusion parameter and diethylenetriaminepentaacetic acid (DTPA), we detected a significant correlation between MeanLin and DTPA (r = -0.502; p = 0.005) in the subgroup of normal-weight donors. The results indicate that signal intensity in CEUS is associated with kidney function in normal-weight individuals. Body mass index (BMI) may be a potential confounder of signal intensity in CEUS. Thus, more research is needed to confirm these results in larger study populations.

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