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.
- MeSH
- chemorezistence * MeSH
- docetaxel * farmakologie terapeutické užití MeSH
- epitelo-mezenchymální tranzice účinky léků MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty * patologie farmakoterapie metabolismus MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Autoři prezentují případ chylózního ascitu, který vznikl po roboticky asistované retroperitoneální lymfadenektomii. Po neúspěšné konzervativní léčbě byla provedena intranodální lymfografie olejovou kontrastní látkou. Po lymfografii došlo k zástavě tvorby ascitu. Danou kazuistikou chceme poukázat na možnost léčby postoperačního chylózního
The authors present a case of chylous ascites that developed after robot-assisted retroperitoneal lymphadenectomy. The intranodal lymphography with an oil-based contrast media was performed due to unsuccessful conservative treatment. After the lymphography chylous ascites ceased. This case report shows the possibility of treating postoperative chylous ascites with a radiological mini-invasive method.
- MeSH
- chylózní ascites * etiologie terapie MeSH
- lidé MeSH
- lymfadenektomie škodlivé účinky MeSH
- lymfatický systém diagnostické zobrazování MeSH
- lymfografie * metody MeSH
- miniinvazivní chirurgické výkony metody MeSH
- pooperační komplikace terapie MeSH
- roboticky asistované výkony * metody MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: Platinum-based chemotherapy followed by the immune checkpoint inhibitor avelumab represents an intensified upfront therapy regimen that may result in significant downstaging and, subsequently, potentially radical robotic nephroureterectomy with a lymph node dissection, an uncommon approach with an unexpectedly favorable outcome. CASE PRESENTATION: We report a case of a 70-year-old female presented with a sizeable cN2+ tumor of the left renal pelvis and achieved deep partial radiologic response after systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance therapy and subsequent robotic resection of the tumor. The patient continued with adjuvant nivolumab therapy once recovered after surgery and remained tumor-free on the subsequent follow-up. The systemic treatment was without any severe adverse reaction. CONCLUSION: We highlight the feasibility of the upfront systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance, robotic-assisted removal of the tumor, and adjuvant immunotherapy with nivolumab. This intensification of the upfront systemic therapy, and the actual treatment sequence significantly increase the chances of prolonged survival or even a cure. This type of personalized therapeutic approach can accelerate future advanced immunotherapeutic strategies.
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
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.
- MeSH
- angiomyolipom patologie chirurgie MeSH
- dospělí MeSH
- karcinom z renálních buněk chirurgie patologie epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * chirurgie patologie MeSH
- nefrektomie * metody MeSH
- oxyfilní adenom patologie chirurgie MeSH
- předoperační období MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Thank you very much for your comment [...].
- MeSH
- beta-alanin * aplikace a dávkování MeSH
- karnosin * MeSH
- lidé MeSH
- potravní doplňky * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- lidé MeSH
- lymfadenektomie škodlivé účinky metody MeSH
- lymfokela * epidemiologie etiologie chirurgie MeSH
- nádory prostaty * patologie MeSH
- prostatektomie škodlivé účinky metody MeSH
- randomizované kontrolované studie jako téma MeSH
- robotika * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Horakova, Lenka, Susi Kriemler, Vladimír Študent, Jacqueline Pichler Hefti, David Hillebrandt, Dominique Jean, Kastė Mateikaitė-Pipirienė, 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. 25:255-265, 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.
- MeSH
- hormonální antikoncepce metody MeSH
- horolezectví fyziologie MeSH
- lidé MeSH
- menstruační cyklus * fyziologie účinky léků MeSH
- nadmořská výška * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Chronická prostatitida/syndrom chronické pánevní bolesti (CP/CPPS - Chronic prostatitis/Chronic pelvic pain syndrome) je onemocnění, které postihuje zejména muže mladšího středního věku. CP/CPPS je definována jako pánevní bolest trvající ≥ 3 měsíce z předchozích 6 měsíců bez jasně identifikovatelné infekční či jiné organické příčiny. Pro široké spektrum příznaků CP/CPPS je často nutné zvolit multimodální léčebný přístup, kdy lze čerpat jak z farmakologické, tak nefarmakologické léčby či jejich kombinace. Zacílení léčby taktéž komplikuje ne zcela objasněná etiologie CP/CPPS. Předkládaná práce si klade za cíl poskytnout souhrnný přehled současných znalostí, informovat o aktuálních možnostech diagnostiky a léčbě CP/CPPS.
Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a disease that mainly affects younger middle-aged men. CP/CPPS is defined as pelvic pain lasting ≥3 months out of the previous 6 months without a clearly identifiable infectious or other organic cause. For the wide spectrum of symptoms of CP/CPPS, it is often necessary to choose a multimodal treatment approach, where both pharmacological and non-pharmacological treatment or a combination of them can be used. Targeting treatment is also complicated as the etiology of CP/CPPS is not yet completely understood. The presented work aims to provide a comprehensive overview of current knowledge, to inform the current possibilities of diagnosis and treatment of CP/CPPS.
- MeSH
- lidé MeSH
- pánevní bolest * diagnóza terapie MeSH
- prostatitida * diagnóza klasifikace terapie MeSH
- urologické látky klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
