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1.
BMC Urol ; 24(1): 175, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174947

RESUMEN

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


Asunto(s)
Neoplasias Renales , Nefrectomía , Humanos , Masculino , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Femenino , Nefrectomía/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/epidemiología , Angiomiolipoma/patología , Angiomiolipoma/cirugía , Adulto , Periodo Preoperatorio , Adenoma Oxifílico/patología , Adenoma Oxifílico/cirugía
3.
Cell Oncol (Dordr) ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162992

RESUMEN

PURPOSE: Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies. METHODS: To address this, we employed a high-throughput single-cell flow cytometry approach to identify a specific surface fingerprint associated with docetaxel-resistance in PCa cells and complemented it with proteomic analysis of extracellular vesicles. We further validated selected antigens using docetaxel-resistant patient-derived xenografts in vivo and probed primary PCa specimens to interrogate of their surface fingerprint. RESULTS: Our approaches revealed a 6-molecule surface fingerprint linked to docetaxel resistance in primary PCa specimens. We observed consistent overexpression of CD95 (FAS/APO-1), and SSEA-4 surface antigens in both in vitro and in vivo docetaxel-resistant models, which was also observed in a cell subpopulation of primary PCa tumors exhibiting EMT features. Furthermore, CD95, along with the essential enzymes involved in SSEA-4 synthesis, ST3GAL1, and ST3GAL2, displayed a significant increase in patients with PCa undergoing docetaxel-based therapy, correlating with poor survival outcomes. CONCLUSION: In summary, we demonstrate that the identified 6-molecule surface fingerprint associated with docetaxel resistance pre-exists in a subpopulation of primary PCa tumors before docetaxel treatment. Thus, this fingerprint warrants further validation as a promising predictive tool for docetaxel resistance in PCa patients prior to therapy initiation.

4.
High Alt Med Biol ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607652

RESUMEN

Horakova, Lenka , Susi Kriemler, Vladimír Student, Jacqueline Pichler Hefti, David Hillebrandt, Dominique Jean, Kaste Mateikaite-Pipiriene, Peter Paal, Alison Rosier, Marija Andjelkovic, Beth Beidlemann, Mia Derstine, and Linda E. Keyes. Hormonal contraception and menstrual cycle control at high altitude: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 00:00-00, 2024. Background: Women who use hormonal contraception (HC) may have questions about their use during travel to high altitude. This scoping review summarizes current evidence on the efficacy and safety of HC and cycle control during high-altitude travel. Methods: We performed a scoping review for the International Climbing and Mountaineering Federation (UIAA) Medical Commission series on Women's Health in the Mountains. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including contraception) with additional publications found by hand search. Results: We identified 17 studies from 7,165 potentially eligible articles. No articles assessed the efficacy of contraception during a short-term high-altitude sojourn. Current data show no advantage or disadvantage in HC users for acclimatization or acute mountain sickness (AMS). Use of HC during high-altitude travel is common and safe for menses suppression. A potential concern of estrogen-containing HC is the increased thrombotic risk, which theoretically could be compounded in hypobaric hypoxia. Conclusions: Evidence is limited for the interaction of HC and high altitude on performance, thrombosis, and contraceptive efficacy. HC does not affect the risk of AMS. The most efficacious and safest method at high altitude is generally the one women are most familiar with and already using.

6.
Eur Urol Focus ; 10(1): 80-89, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37541915

RESUMEN

CONTEXT: Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies. OBJECTIVE: To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence. EVIDENCE ACQUISITION: In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints. EVIDENCE SYNTHESIS: Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low. CONCLUSIONS: PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC. PATIENT SUMMARY: A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap.


Asunto(s)
Linfocele , Neoplasias de la Próstata , Robótica , Masculino , Humanos , Linfocele/epidemiología , Linfocele/etiología , Linfocele/cirugía , Neoplasias de la Próstata/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Prostatectomía/efectos adversos , Prostatectomía/métodos
7.
Cancers (Basel) ; 15(15)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37568671

RESUMEN

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.

8.
Front Oncol ; 13: 1115901, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37519822

RESUMEN

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

9.
Nutrients ; 15(7)2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37049610

RESUMEN

The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite N-acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of Helicobacter pylori eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.


Asunto(s)
Carnosina , Humanos , Carnosina/uso terapéutico , Antioxidantes/metabolismo , Suplementos Dietéticos , Dipéptidos/metabolismo , Músculo Esquelético/metabolismo , beta-Alanina/farmacología , beta-Alanina/metabolismo
10.
Eur J Med Chem ; 249: 115086, 2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36682291

RESUMEN

High expression of the androgen receptor (AR) and the disruption of its regulation are strongly responsible for the development of prostate cancer (PCa). Therapeutically relevant non-steroidal or steroidal antiandrogens are able to block the AR effect by eliminating AR-mediated signalling. Herein we report the synthesis of novel steroidal pyrazoles derived from the natural sex hormone 5α-dihydrotestosterone (DHT). 2-Ethylidene or 2-(hetero)arylidene derivatives of DHT obtained by regioselective Claisen-Schmidt condensation with acetaldehyde or (hetero)aromatic aldehydes in alkaline ethanol were reacted with monosubstituted hydrazines to give A-ring-fused 1,5-disubstituted pyrazoles as main or exclusive products, depending on the reaction conditions applied. Spontaneous or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)-induced oxidation of the primarily formed pyrazolines resulted in the desired products in moderate to good yields, while 17-oxidation also occurred by using the Jones reagent as a strong oxidant. Transcriptional activity of the AR in a reporter cell line was examined for all novel compounds, and several previously synthesized similar DHT-based pyrazoles with differently substituted heteroring were also included to obtain information about the structure-activity relationship. Two specific regioisomeric groups of derivatives significantly diminished the transcriptional activity of the AR in reporter cell line in 10 µM concentration, and displayed reasonable antiproliferative activity in AR-positive PCa cell lines. Lead compound (3d) was found to be a potent AR antagonist (IC50 = 1.18 µM), it generally suppressed AR signalling in time and dose dependent manner, moreover, it also led to a sharp decrease in wt-AR protein level probably caused by proteasomal degradation. We confirmed the antiproliferative activity of 3d in AR-positive PCa cell lines (with GI50 in low micromolar ranges), and its cellular, biochemical and in silico binding in AR ligand-binding domain. Moreover, compound 3d was shown to be potent even ex vivo in patient-derived tissues, which highlights the therapeutic potential of A-ring-fused pyrazoles.


Asunto(s)
Dihidrotestosterona , Neoplasias de la Próstata , Masculino , Humanos , Dihidrotestosterona/farmacología , Dihidrotestosterona/metabolismo , Receptores Androgénicos/metabolismo , Pirazoles , Regulación hacia Abajo , Línea Celular Tumoral , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Esteroides/uso terapéutico
11.
Eur Urol ; 83(2): 154-162, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36041934

RESUMEN

BACKGROUND: Symptomatic lymphoceles present the most common complication of robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND). No surgical technique has so far shown success in reducing the incidence rate, but several retrospective studies have shown the beneficial effect of the fixation of the peritoneum. OBJECTIVE: To introduce a modification in the technique of fixing the peritoneum to the pubic bone and to confirm whether this intervention reduces the incidence of lymphoceles. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized (1:1) single-center one-sided blind study was conducted in patients with localized prostate cancer (cT1-2cN0M0) indicated for RARP with ePLND operated between December 2019 and June 2021. In the intervention group, the free flap of the peritoneum was fixed to the pubic bone. In the control group, the peritoneal flap was left free without fixation. SURGICAL PROCEDURE: In the intervention group, the free flap of the peritoneum was fixed to the pubic bone (PerFix) so that lateral holes were left, allowing drainage of lymph from the pelvis into the abdominal cavity, where it would be resorbed. The iliac vessels and obturator fossa remained uncovered by the peritoneum and the bladder. MEASUREMENTS: The primary objective was to evaluate the frequency of symptomatic lymphoceles during follow-up. The secondary endpoints were the radiological presence of lymphoceles on computed tomography of the pelvis carried out 6 wk after surgery, the volume of the lymphoceles, and the degree of severe (Clavien-Dindo ≥3) complications. RESULTS AND LIMITATIONS: Of the 260 randomized patients, 245 were evaluated in the final analysis-123 in the intervention and 122 in the control group. The median follow-up was 595 d. There were no differences between the groups regarding clinical and pathological variables. The median of 17 nodes removed was the same in both groups (p = 0.961). Symptomatic lymphoceles occurred in 17 patients (6.9%), while in the intervention group these were found in three (2.4%) versus 14 (11.5%) in the control group (p = 0.011). The number of radiologically detected asymptomatic lymphoceles did not differ (p = 0.095). There was no significant difference in lymphocele volume between the two groups (p = 0.118). The rate of serious complications (Clavien 3a and 3b) was 4.8% in the intervention group and 9.1% in the control group (p = 0.587). A multivariate logistic regression model of symptomatic lymphocele occurrence was created with significant factors: body mass index (odds ratio [OR] = 1.1, 95% confidence interval [CI] = [1.03, 1.26], p = 0.012) and intervention (OR = 4.6, 95% CI = [1.28, 16.82], p = 0.02). CONCLUSIONS: Fixation of the peritoneum (PerFix) reduced the incidence of symptomatic lymphoceles in RARP with ePLND. We found no difference in the frequency of asymptomatic lymphocele development. The volume of the detected lymphoceles was similar. PATIENT SUMMARY: In this study, we compared the rate of development of postoperative complications using the peritoneal fixation technique with that of a nonfixation control group for robot-assisted radical prostatectomy with extended pelvic lymphadenectomy. Fixation of the peritoneum should obviate the development of severe complications in the postoperative period.


Asunto(s)
Colgajos Tisulares Libres , Linfocele , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Masculino , Humanos , Linfocele/etiología , Linfocele/prevención & control , Peritoneo/patología , Peritoneo/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Pelvis/patología , Colgajos Tisulares Libres/patología
12.
Cancers (Basel) ; 14(19)2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36230546

RESUMEN

PURPOSE: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. METHODS: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. RESULTS: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844-0.954), while for urine samples it was 0.867 (0.763-0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832-0.952) and 0.981 (0.956-0.998), respectively. CONCLUSION: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models.

13.
Curr Oncol ; 29(8): 5475-5488, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-36005171

RESUMEN

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


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Sarcoma , Neoplasias de los Tejidos Blandos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Humanos , Ipilimumab/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Nefrectomía , Nivolumab/uso terapéutico
14.
Am J Pathol ; 192(9): 1321-1335, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35750257

RESUMEN

Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumors, including prostate cancer (PCa), and have described its role primarily in the proinflammatory response and induction of apoptosis. It is up-regulated in some castration-resistant prostate cancers. However, the role of TLR3 in prostate cancer progression remains largely unknown. The current study experimentally demonstrated that exogenous TLR3 activation in PCa cell lines leads to a significant induction of secretion of the cytokines IL-6, IL-8, and interferon-ß, depending on the model and chemoresistance status. Transcriptomic analysis of TLR3-overexpressing cells revealed a functional program that is enriched for genes involved in the regulation of cell motility, migration, and tumor invasiveness. Increased motility, migration, and invasion in TLR3-overexpressing cell line were confirmed by several in vitro assays and using an orthotopic prostate xenograft model in vivo. Furthermore, TLR3-ligand induced apoptosis via cleavage of caspase-3/7 and poly (ADP-ribose) polymerase, predominantly in TLR3-overexpressing cells. These results indicate that TLR3 may be involved in prostate cancer progression and metastasis; however, it might also represent an Achilles heel of PCa, which can be exploited for targeted therapy.


Asunto(s)
Neoplasias de la Próstata , Receptor Toll-Like 3 , Animales , Apoptosis , Línea Celular Tumoral , Humanos , Masculino , Poli I-C/farmacología , Próstata/patología , Neoplasias de la Próstata/patología , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/metabolismo
15.
Medicina (Kaunas) ; 58(3)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35334512

RESUMEN

Background and Objectives: Complete pathological response after ipilimumab and nivolumab combination therapy in a patient with intermediate prognosis renal cell carcinoma is an uncommon finding. Case presentation: A 60-year-old man presented with synchronous solitary metastatic bone lesion and renal cell carcinoma and achieved a complete pathological response after surgical resection of the bone lesion, followed by ipilimumab and nivolumab combination therapy and nephrectomy. The treatment was complicated by hypophysitis and oligoarthritis more than a year after the initiation of the therapy. Conclusions: Currently, the combination therapy based on immune checkpoint inhibitors represents the treatment of choice in patients with intermediate- and poor-risk prognosis metastatic renal cell carcinoma. In the present case, preoperative therapy with ipilimumab and nivolumab resulted in a complete pathological response in the renal tumor. Vigilance concerning potential immune-related side effects is warranted throughout the course of therapy and the subsequent follow-up.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Ipilimumab/efectos adversos , Ipilimumab/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Nivolumab
16.
Ceska Gynekol ; 87(1): 40-42, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35240835

RESUMEN

OBJECTIVE: To present a case of isolated fluidothorax as a symptom of atypical late ovarian hyperstimulation syndrome. METHODS: Review of available information and presentation of our case observed at the Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University and University Hospital Bulovka. GnRH antagonist protocol was used to stimulate the patient and fresh embryo transfer was performed. Sixteenth day after the oocyte retrieval the patient was examined due to dyspnoea and lab exam proved ovarian hyperstimulation syndrome. CONCLUSION: Late ovarian hyperstimulation syndrome can lead to isolated fluidothorax in case of additional favourable conditions.


Asunto(s)
Síndrome de Hiperestimulación Ovárica , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina , Humanos , Recuperación del Oocito/métodos , Síndrome de Hiperestimulación Ovárica/complicaciones , Síndrome de Hiperestimulación Ovárica/diagnóstico , Inducción de la Ovulación/efectos adversos , Inducción de la Ovulación/métodos , Embarazo
17.
Artículo en Inglés | MEDLINE | ID: mdl-35147136

RESUMEN

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


Asunto(s)
Hidronefrosis , Obstrucción Ureteral , Sistema Urinario , Biomarcadores , Niño , Femenino , Humanos , Hidronefrosis/diagnóstico , Hidronefrosis/etiología , Hidronefrosis/terapia , Recién Nacido , Riñón/diagnóstico por imagen , Embarazo , Obstrucción Ureteral/diagnóstico por imagen , Obstrucción Ureteral/etiología , Sistema Urinario/diagnóstico por imagen
18.
Obstet Gynecol ; 138(6): 828-837, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34735382

RESUMEN

OBJECTIVE: To compare disease-free survival between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer. METHODS: We conducted a multicentric, propensity-matched study of patients with high-risk endometrial cancer who underwent hysterectomy, bilateral salpingo-oophorectomy, and staging between January 1999 and June 2016 at two centers. High-risk endometrial cancer included grade 3 endometrioid, serous, clear cell, undifferentiated carcinoma or carcinosarcoma with any myometrial invasion. Patients were categorized a priori into two groups based on surgical approach, propensity scores were calculated based on potential confounders and groups were matched 1:1 using nearest neighbor technique. Cox hazard regression analysis and Kaplan-Meier curves evaluated the association of surgical technique with survival. RESULTS: Of 626 eligible patients, 263 (42%) underwent minimally invasive surgery and 363 (58%) underwent open surgery. In the matched cohort, there were no differences in disease-free survival rates at 5 years between open (53.4% [95% CI 45.6-60.5%]) and minimally invasive surgery (54.6% [95% CI 46.6-61.8]; P=.82). Minimally invasive surgery was not associated with worse disease-free survival (hazard ratio [HR] 0.85, 95% CI 0.63-1.16; P=.30), overall survival (HR 1.04, 95% CI 0.73-1.48, P=.81), or recurrence rate (HR 0.99; 95% CI 0.69-1.44; P=.99) compared with open surgery. Use of uterine manipulator was not associated with worse disease-free survival (HR 1.01, 95% CI 0.65-1.58, P=.96), overall survival (HR 1.18, 95% CI 0.71-1.96, P=.53), or recurrence rate (HR 1.12, 95% CI 0.67-1.87; P=.66). CONCLUSION: There was no difference in oncologic outcomes comparing minimally invasive and open surgery among patients with high-risk endometrial cancer.


Asunto(s)
Carcinoma/cirugía , Carcinosarcoma/cirugía , Neoplasias Endometriales/cirugía , Histerectomía/mortalidad , Salpingooforectomía/mortalidad , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Carcinosarcoma/mortalidad , Carcinosarcoma/patología , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Estadificación de Neoplasias , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Salpingooforectomía/métodos , Resultado del Tratamiento
20.
Urolithiasis ; 49(1): 73-79, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33164114

RESUMEN

The aims of the study were to compare the change in the Wisconsin Stone Quality of Life (WISQOL) score in patients who underwent retrograde intrarenal surgery (RIRS) single-use ureteroscope or extracorporeal shock wave lithotripsy (ESWL) with a calculation of quality-adjusted life-years (QALYs). 158 patients treated with urinary stone disease were randomly divided into 80 patients in the validation and 78 patients in the intervention arm. Patients in the intervention arm were randomly divided into the RIRS or the ESWL group. Linguistic validation of the WISQOL into the Slovak language was performed using a standardised multistep process. Discriminant validity was assessed by comparing stone-forming patients to an additional 34 healthy individuals. Patients were asked to fill in the WISQOL before and in the 24th week after the intervention. The QALYs were calculated by the formula QALY = weight factor (WF) x time period after intervention. The Cronbach's α of the WISQOL was 0.94, the Pearson's coefficient for test-retest reliability was 0.91, and the discriminant validity confirmed a higher score for healthy individuals (p < 0.001). The median WISQOL score changed from 45.5 to 95.5 vs. 33.9 to 87.1 in the RIRS and ESWL groups, respectively (p < 0.001). Patients from the RIRS group had a good possibility of reaching 19.727 QALYs gained during life expectancy compared to 15.780 for the ESWL group (p < 0.001). RIRS single-use ureteroscope is significantly superior to ESWL in reaching more QALYs gained during life expectancy. The WISQOL Slovak version is valid, reliable and strictly specific for stone-forming patients.


Asunto(s)
Litotricia/estadística & datos numéricos , Calidad de Vida , Encuestas y Cuestionarios/estadística & datos numéricos , Ureteroscopía/estadística & datos numéricos , Cálculos Urinarios/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psicometría/métodos , Años de Vida Ajustados por Calidad de Vida , Reproducibilidad de los Resultados , Traducción , Resultado del Tratamiento , Ureteroscopios , Ureteroscopía/instrumentación , Cálculos Urinarios/complicaciones , Cálculos Urinarios/psicología
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