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PURPOSE: This study seeks to contribute real-world data on the prevalence of BRCA1/2 and HRR gene mutations in prostate cancer. METHODS: We compiled sequencing data of 197 cases of primary and metastatic prostate cancer, in which HRR mutation analysis was performed upon clinical request within the last 5 years. All cases were analyzed using a targeted NGS BRCAness multigene panel, including 8 HRR genes (ATM, BRCA1, BRCA2, CDK12, CHEK2, FANCA, HDAC2, PALB2). RESULTS: Our findings reveal a prevalence of potentially targetable mutations based on FDA criteria of 20.8%, which is comparable to the literature. However, the frequency of targetable BRCA2 mutations within our cohort was lower than reported for mCRPC and ATM and CHEK2 mutations were more prevalent instead. Thus, while 20.8% (n = 38) of the cases meet the criteria for olaparib treatment per FDA approval, only 4.9% (n = 9) align with the eligibility criteria according to the EMA approval. CONCLUSION: This study offers valuable real-world insights into the landscape of BRCA1/2 and HRR gene mutations and the practical clinical management of HRR gene testing in prostate cancer, contributing to a better understanding of patient eligibility for PARPi treatment.
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Mutação , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Pessoa de Meia-Idade , Proteína BRCA2/genética , Genes BRCA2 , Proteína BRCA1/genética , Genes BRCA1 , Metástase Neoplásica , Idoso de 80 Anos ou mais , PrevalênciaRESUMO
BACKGROUND: Canonical androgen receptor (AR) signaling regulates a network of DNA repair genes in prostate cancer (PCA). Experimental and clinical evidence indicates that androgen deprivation not only suppresses DNA repair activity but is often synthetically lethal in combination with PARP inhibition. The present study aimed to elucidate the impact of AR splice variants (AR-Vs), occurring in advanced or late-stage PCA, on DNA repair machinery. METHODS: Two hundred and seventy-three tissue samples were analyzed, including primary hormone-naïve PCA, primary metastases, hormone-sensitive PCA on androgen deprivation therapy (ADT) and castration refractory PCA (CRPC group). The transcript levels of the target genes were profiled using the nCounter platform. Experimental support for the findings was gained in AR/AR-V7-expressing LNCaP cells subjected to ionizing radiation. RESULTS: AR-Vs were present in half of hormone-sensitive PCAs on androgen deprivation therapy (ADT) and two-thirds of CRPC samples. The presence of AR-Vs is highly correlated with increased activity in the AR pathway and DNA repair gene expression. In AR-V-expressing CRPC, the DNA repair score increased by 2.5-fold as compared to AR-V-negative samples. Enhanced DNA repair and the deregulation of DNA repair genes by AR-V7 supported the clinical data in a cell line model. CONCLUSIONS: The expression of AR splice variants such as AR-V7 in PCA patients following ADT might be a reason for reduced or absent therapy effects in patients on additional PARP inhibition due to the modulation of DNA repair gene expression. Consequently, AR-Vs should be further studied as predictive biomarkers for therapy response in this setting.
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BACKGROUND: Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary. METHODS: In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety. RESULTS: A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B. CONCLUSIONS: AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P.
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Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/efeitos adversos , Prednisona , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , Antígeno Prostático Específico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hormônio Liberador de Gonadotropina/uso terapêutico , Testosterona/uso terapêuticoAssuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Humanos , Masculino , Acetato de Abiraterona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Ensaios Clínicos Fase III como Assunto , Metanálise como Assunto , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Prednisolona/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Radical cystectomy (RC) with urinary diversion is a challenging surgical intervention. There is significant risk of postoperative complications, particularly linked to urinary diversion and the patient's comorbidities. The surgeon and the multidisciplinary team need to be familiar with all potential complications. In order to achieve optimal oncological and functional outcomes, multiple factors have to be considered during perioperative management, including the adherence to evidence-based guidelines, standardised concepts of enhanced recovery and best surgical practice for RC and urinary diversion. All measures should aim to minimise complication rates after RC and to accelerate recovery. We summarise essential Dos and Don'ts when performing RC with different forms of urinary diversion.
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Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversosRESUMO
Data on robotic retroperitoneal lymph node dissection (R-RPLND) for metastatic testicular germ cell tumours (mTGCTs) are scarce and the use of R-RPLND itself is still under debate. The aim of our study was to evaluate the indications, feasibility and outcomes of R-RPLND, with special emphasis on differences between primary R-RPLND (pR-RPLND) and post-chemotherapeutic R-RPLND (pcR-RPLND) in mTGCTs. We retrospectively analysed the data of patients who underwent R-RPLND for mTGCT between November 2013 and September 2019 in two centres in Germany. Indications, operative technique, intra- and postoperative complications and oncologic outcome were analysed. Twenty-three mTGCT patients underwent R-RPLND (7 pR-RPLND, 16 pcR-RPLND). For pR-RPLND versus pcR-RPLND, median time of surgery was 243 min [interquartile range (IQR) 123-303] versus 359 min (IQR 202-440, p = 0.154) and median blood loss 100 mL (IQR 50-200) versus 275 mL (IQR 100-775, p = 0.018). Intra- and postoperative complications were more frequent in pcR-RPLND (pcR-RPLND: intra/post: 44%/44%; pR-RPLND: intra/post: 0%/29%). However, these were only statistically significant in the case of intraoperative complications (intra: p = 0.036, post: p = 0.579). Intraoperative complications (n = 7), conversions (n = 4) and transfusions (n = 4) occurred in pcR-RPLND patients only. After a median follow-up of 16.3 months (IQR 7.5-35.0) there were no recurrences or deaths. R-RPLND displays a valuable, minimally invasive treatment option in mTGCT. However, R-RPLND is challenging and pcR-RPLND especially bears a considerable risk of complications. This operation should be limited to patients with an easily accessible residual tumour mass and to surgeons experienced in robotic surgery and TGCT treatment.
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Excisão de Linfonodo , Linfonodos/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Espaço Retroperitoneal/patologia , Neoplasias Testiculares/diagnóstico , Adulto , Tomada de Decisão Clínica , Gerenciamento Clínico , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/cirurgia , Estudos Retrospectivos , Neoplasias Testiculares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Salvage lymph node dissection (sLND) - performed open or minimally-invasive - is a treatment modality that can be offered to patients with nodal recurrence after radical prostatectomy (RP), especially in times where modern imaging methods like choline- or PSMA-PET/CT are available. Yet, there are only very limited data on the safety and oncological effectiveness of robotic sLND. METHODS: We retrospectively identified patients who underwent robotic sLND at our institution between 2013 and 2017 for nodal recurrence after RP, which had been diagnosed either by 18F-choline- or 68Ga-PSMA-PET/CT. We analyzed perioperative data and early oncological outcomes with a focus on the comparison of patients with preoperative choline- vs. those with preoperative PSMA-PET/CT. RESULTS: We identified 36 patients who underwent robotic sLND at a median time of 45.3 months [range 3.1;228.6] after RP, with nodal recurrences detected in 25 patients by PSMA- and in 11 by choline-PET/CT. Median preoperative PSA, operation time and blood loss were 1.98 ng/ml [range 0.09;35.15], 129.5 min [range 65;202] and 50 ml [range 0;400], respectively. No high-grade complications occurred. A median number of 6.5 [range 1;25] lymph nodes were removed with a median of 1 [range 0;9] tumor-occupied node. None of the patients received any adjuvant treatment. Median postoperative PSA-change was -57% [range -100; +58] in the PSMA- and +10% [range -91; +95] in the choline-group (p = 0.015). 44% of patients in the PSMA- and 18% of patients in the choline-group experienced complete biochemical response (cBCR; PSA <0.2 ng/ml). Median time from sLND to the initiation of further therapy was 12 months [range 2;21.5] in the PSMA-group and 4.7 months [range 2.2;18.9] in the choline-group (p = 0.001). CONCLUSIONS: This is the hitherto largest series on robotic sLND for nodal recurrence after RP. Robotic sLND is a feasible therapeutic option with low morbidity, which can at least delay the initiation of further therapy - in some patients up to several years. However, the extend of sLND has to be standardized and randomized trials are needed to finally define the oncological effectiveness of this approach.
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Excisão de Linfonodo/métodos , Recidiva Local de Neoplasia/cirurgia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Terapia de Salvação , Cirurgia Assistida por Computador , Idoso , Idoso de 80 Anos ou mais , Colina/análogos & derivados , Seguimentos , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. METHODS: We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (nâ¯=â¯129) or benign prostatic hyperplasia (BPH) (nâ¯=â¯73) who were recruited just after the first diagnosis. RESULTS: In younger subjects <65â¯years, concentrations of (6S)-5-CH3-H4folate (15.3 vs. 17.7â¯nmol/L) or total folate (UPLC-MS/MS) (18.7 vs. 23.0â¯nmol/L) did not differ between men with BPH and those with PCa, while SAM was higher in the controls (128 vs. 116â¯nmol/L). Younger patients with low- and high grade cancer did not differ in (6S)-5-CH3-H4folate (17.8 vs. 17.3â¯nmol/L) or total folate (UPLC-MS/MS) (22.9 vs. 23.3â¯nmol/L), but SAM was lower in patients with low grade PCa (111 vs. 126â¯nmol/L). In the older group ≥65â¯years, (6S)-5-CH3-H4folate (18.4 vs. 18.2â¯nmol/L) and total folate (UPLC-MS/MS) (22.5 vs. 22.1â¯nmol/L) did not differ between BPH and PCa. Older patients with advanced tumors had lower (6S)-5-CH3-H4folate compared with those with low grade tumor (12.8 vs. 20.0â¯nmol/L: pâ¯=â¯0.013). Plasma SAM was not different between older patients and controls and was not related to PCa grade. CONCLUSIONS: Lowered serum methyl folate measured at the time of diagnosis in older patients with advanced PCa, and lowered plasma SAM in younger patients with low grade PCa suggest differential folate metabolism that may have mechanistic, prognostic or predictive values.
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Deficiência de Ácido Fólico/fisiopatologia , Ácido Fólico/análogos & derivados , Estado Nutricional , Próstata/patologia , Hiperplasia Prostática/etiologia , Neoplasias da Próstata/etiologia , S-Adenosilmetionina/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Regulação para Baixo , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/metabolismo , Alemanha/epidemiologia , Hospitais Universitários , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Gradação de Tumores , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Risco , S-Adenosil-Homocisteína/sangueRESUMO
BACKGROUND: Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed. METHODS: A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up. RESULTS: Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270-490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18-35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)-all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons. CONCLUSION: In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life.
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Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Transplante de Rim , Nefrectomia , Néfrons/cirurgia , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Adulto JovemRESUMO
The incidence of segmental testicular infarction (STI) is very low. Such a disorder most often affects young men. The most common symptom is sudden testicular pain. We report 6 cases of men diagnosed with STI. Clinical examination, blood test, urine analysis, and ultrasound examination with colour Doppler were performed. Furthermore, tissue sonoelastography or MRI was performed in selected patients. All men underwent surgical exploration. In all but one man, the affected testis was preserved. Although STI is a rare condition, it should be taken into account if testicular pain prior to suspicious ultrasound imaging occurs. To be aware of this benign testicular pathology and its clinical and imaging features is important to avoid unnecessary orchiectomies in young patients.
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Infarto/diagnóstico por imagem , Doenças Testiculares/diagnóstico por imagem , Testículo/diagnóstico por imagem , Dor Aguda , Adulto , Técnicas de Imagem por Elasticidade , Humanos , Imageamento por Ressonância Magnética , Masculino , Orquiectomia , Testículo/cirurgia , Ultrassonografia Doppler , Urinálise , Doenças Vasculares , Adulto JovemRESUMO
INTRODUCTION: We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard®, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany. MATERIALS AND METHODS: Data was pooled from 2 prospective, open-label, non-interventional studies in which 1,906 patients were treated for 12 months with either the 3-month (n = 633) or 6-month (n = 1,273) LA formulation. RESULTS: Median prostate-specific antigen levels in the pooled patient population declined from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific antigen reduction was achieved in treatment-naïve and pre-treated patients. Adverse events were documented in 8.8% of patients. CONCLUSIONS: These pooled data from routine clinical practice in Germany indicate that LA 3- and 6-month depot injections can effectively reduce prostate-specific antigen levels in a broad patient population with advanced prostate cancer.
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Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Antineoplásicos Hormonais/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Alemanha , Humanos , Leuprolida/efeitos adversos , Masculino , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Próstata/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC. METHODS/DESIGN: The trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy. DISCUSSION: This multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02077634 . Registered on 9 December 2013.
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Acetato de Abiraterona/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hormônio Liberador de Gonadotropina/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Inibidores da Síntese de Esteroides/administração & dosagem , Acetato de Abiraterona/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Alemanha , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Masculino , Metástase Neoplásica , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Fatores de Risco , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Esteroide 17-alfa-Hidroxilase/metabolismo , Inibidores da Síntese de Esteroides/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Muscle-invasive bladder cancer (MIBC) represents a highly aggressive tumor type compared to non-muscle-invasive tumors. MIBC is characterized by specific molecular alterations, which may also modulate extracellular tumorigenic effects. Tumor-associated exosomes, especially exosomal miRNAs, are important regulators in the interaction between tumor cells and tumor microenvironment by affecting tumor-promoting processes in target cells. It is important to analyze whether their exosomal patterns also reflect the specific molecular characteristics of MIBC. The aim of this study was to compare the miRNA expression in secreted exosomes from urinary bladder cancer cells (UBC) with different degrees of invasiveness. By electron microscopy, nanotracking analysis and western blot we proofed a high quality of isolated exosomes. Microarray analysis identified an invasion-associated signature of 15 miRNAs, which is significantly altered in exosomes of invasive UBC compared to non-invasive counterparts. Therefrom, 9 miRNAs are consistent differently expressed in both, invasive cells and their secreted exosomes. The remaining 6 exosome-specific miRNAs are only deregulated in exosomes but not in their parental cells. MiRNA alterations were verified by qPCR in cell culture and urinary exosomes. In conclusion, we showed that exosomes from invasive UBC cells are characterized by a specific miRNA signature. Further analyses have to clarify the functional relevance of exosomal miRNAs secreted by invasive bladder cancer cells for modification of the tumor microenvironment and their putative role as molecular markers in liquid biopsies.
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OBJECTIVES: To compare robot-assisted laparoscopic adrenalectomy (RALA) and open adrenalectomy (OA) with regard to intra-operative complications, peri-operative outcome and cost effectiveness. SUBJECTS AND METHODS: Functional and statistical data from patients who underwent OA or RALA between 2001 and 2015 were prospectively recorded including intra- and postoperative outcomes. Data on per-day costs from current census reports (540/day and 1 145/day for normal and intermediate care [IMC]) were also used to evaluate treatment costs. Additional costs for RALA were assumed at 2288 as reported in the current literature. Patients were matched by American Society of Anesthesiologists score, age, side of surgery and gender for comparison of OA and RALA. A total of 28 matched pairs were analysed with regard to patient characteristics, peri-operative outcomes and cost-effectiveness. Statistical significance of outcome variables was determined using Student's t-test and Pearson's chi-squared test. RESULTS: As a result of the matching process, patient groups did not differ in their main characteristics. Length of hospital stay was shorter for RALA than for OA (11.1 ± 4.8 vs 6.8 ± 1.2 days; P < 0.01) as was IMC treatment (2.3 ± 1.7 vs 1.2 ± 0.4 days; P < 0.01). The mean operating time was longer for RALA (128.5 ± 46.5 vs 102.2 ± 44.5 min; P = 0.03), but the last 10 RALA procedures (mean: 97.1 ± 35.2 min) were similar to OA. The rate of complications was similar in the two groups. Estimated costs were 8 627.5 for OA and 7 334 for RALA. CONCLUSIONS: The study showed that RALA was safe and cost-effective compared with OA. Increasing experience leads to similar operating times, putting high-volume centres at an advantage.
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Adrenalectomia/economia , Adrenalectomia/métodos , Análise Custo-Benefício , Laparoscopia , Procedimentos Cirúrgicos Robóticos/economia , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS: DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing. RESULTS: Kaplan-Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC-WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed. CONCLUSIONS: The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neovascularização Patológica/genética , Polimorfismo de Nucleotídeo Único , Pirróis/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , SunitinibeRESUMO
BACKGROUND: Choline is an important source of phospholipids and methyl groups in mammalian cells. High demands for methyl and phospholipids in malignant cells suggest that choline metabolism may be disturbed in patients with cancer. OBJECTIVES AND METHODS: This case-control study investigated differences in concentrations of choline metabolites between 80 elderly men (age ≥ 65 years) with prostate cancer (PCa) and 51 men with benign prostatic hyperplasia (BPH). Plasma/serum concentrations of free choline, betaine, dimethylglycine, folate, total homocysteine (tHcy), cystathionine, methylmalonic acid, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), and phospholipids were measured. RESULTS: Men with BPH and those with PCa showed no significant differences in the concentrations of free choline (median = 9.7 vs. 10.0 µmol/L), folate (17.4 vs. 19.8 nmol/L), tHcy (16.0 vs. 16.2 µmol/L), SAH (18.8 vs. 18.2 nmol/L), and phosphatidylcholine (1634 vs. 1610 µmol/L). The concentrations of methylmalonic acid were lower in men with PCa (203 vs. 228 nmol/L) but the difference was not significant after adjusting for age. Sphingomyelin species (16:0, 18:0, 18:1, 20:0, 22:0, 22; 1, 23:0, 23:1, 24:0, 24:1, and 24:2) were significantly lower in men with PCa than in the controls (6-16% differences). Multiple regression analyses showed that the presence of PCa, statin use, choline, age, cystathionine, and methylmalonic acid were significant negative determinant of sphingomyelins, whereas phosphatidylcholine was a strong positive determinant. CONCLUSIONS: The current results support systemic alterations in phospholipids metabolism in PCa. We report on a significant decrease in plasma concentrations of sphingomyelin in elderly patients with PCa and in users of statins. The PCa-associated low sphingomyelin showed a synergy with the effect of statins. The presence of PCa was not associated with significant changes in plasma concentrations of choline or methyl metabolites. However, changes in choline absorption and tissue uptake cannot be ruled out in this study.