BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.
- MeSH
- antigeny nádorové MeSH
- dospělí MeSH
- karboanhydrasa IX metabolismus genetika MeSH
- karcinom z renálních buněk * patologie metabolismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondriální DNA genetika metabolismus MeSH
- mitochondrie * metabolismus patologie genetika MeSH
- mutace MeSH
- nádorový supresorový protein VHL genetika metabolismus MeSH
- nádory ledvin * patologie metabolismus genetika MeSH
- respirační komplex II * metabolismus genetika MeSH
- senioři MeSH
- sukcinátdehydrogenasa genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.
- MeSH
- karcinom z přechodných buněk * diagnóza diagnostické zobrazování terapie patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nádory ledvin diagnostické zobrazování terapie diagnóza patologie MeSH
- nádory močovodu diagnostické zobrazování diagnóza terapie patologie MeSH
- počítačová rentgenová tomografie metody MeSH
- pozitronová emisní tomografie metody MeSH
- staging nádorů MeSH
- urologické nádory diagnóza diagnostické zobrazování terapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.
Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.
- MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- epigeneze genetická MeSH
- epitelo-mezenchymální tranzice * genetika MeSH
- glutathion-S-transferasa fí genetika metabolismus MeSH
- histonlysin-N-methyltransferasa genetika metabolismus MeSH
- karcinogeneze * genetika MeSH
- lidé MeSH
- metylace DNA * MeSH
- multiomika MeSH
- mutace * MeSH
- nádorové supresorové proteiny genetika metabolismus MeSH
- nádory ledvin * genetika patologie MeSH
- regulace genové exprese u nádorů MeSH
- stárnutí genetika MeSH
- thiolesterasa ubikvitinu MeSH
- transkripční faktory genetika metabolismus MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.
- MeSH
- analýza přežití MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- zánět patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of renal neoplasm predominantly affecting younger individuals. It is characterized by germline mutations in SDHx genes, particularly type B. Histologically, SDH-deficient RCC features eosinophilic cytoplasmic cells forming solid nests or microcysts, sometimes entrapping normal tubules. We present three SDH-deficient RCC cases with overlapping morphological features with fumarate hydratase-deficient RCC and TFEB-rearranged RCC, an appearance that has not been previously described. All tumors lacked SDHB expression and harbored pathogenic SDHB mutations, with the germline nature confirmed in two cases. Metastasis developed in two patients. Our case set highlights the diagnostic challenges of molecularly defined renal tumors and expands the morphological spectrum of SDH-deficient RCC with unusual histological features. Clinically, these tumors appear to be aggressive.
- MeSH
- dediferenciace buněk MeSH
- dospělí MeSH
- fumarasa nedostatek genetika MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika analýza MeSH
- nádory ledvin * patologie genetika MeSH
- sukcinátdehydrogenasa * nedostatek genetika MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Renální karcinom se ve zvýšené míře vyskytuje v rozvinutých zemích Evropy a Severní Ameriky, pro které je typický vysoký finanční příjem a tzv. západní životní styl. S ním souvisí výskyt metabolického syndromu a jeho komponent, které mají vliv nejen na kardiovaskulární onemocnění a cukrovku, ale rovněž na vznik maligních nádorů. U renálního karcinomu jsou typickými rizikovými faktory obezita a hypertenze. Přehledový článek popisuje vztah mezi známými metabolickými rizikovými faktory a karcinogenezí zhoubných nádorů ledvin, současně diskutuje i možné preventivní strategie, jak zlepšit metabolickou dysfunkci a snížit tak riziko vzniku (nejen) renálního karcinomu.
Renal cell carcinoma is common in developed countries in Europe and North America. These regions are characterized by high income and the so-called "western" lifestyle which is associated with the occurrence of metabolic syndrome and its components. These have an impact not only on cardiovascular disease and diabetes, but also on the development of malignant tumours. Obesity and hypertension are typical risk factors for renal cell carcinoma. This review describes the relationship between known metabolic risk factors and renal cancer carcinogenesis, while also discussing possible preventive strategies to improve metabolic dysfunction and thus reduce the risk of (not only) renal cell carcinoma.
- MeSH
- diabetes mellitus 2. typu diagnóza farmakoterapie komplikace metabolismus MeSH
- karcinom z renálních buněk * diagnóza etiologie metabolismus MeSH
- lidé MeSH
- metabolický syndrom * diagnóza komplikace MeSH
- obezita komplikace metabolismus MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Prezentujeme kazuistiku pacienta s lokalizovaným světlobuněčným renálním karcinomem, kterému byla provedena kurativní radikální nefrektomie vlevo. S odstupem 9 let byla zjištěna metastáza renálního karcinomu do prostaty a následně byl verifikován metastatický proces do plic.
We present a case report of patient with localised clear renal cell carcinoma who underwent left side radical nephrectomy. Nine years later, a metastasis of renal cell carcinoma to the prostate was detected, and subsequently metastatic process to the lungs was verified.
- MeSH
- karcinom z renálních buněk * diagnostické zobrazování diagnóza sekundární MeSH
- lidé MeSH
- nádory plic diagnóza sekundární MeSH
- nádory prostaty * diagnóza sekundární MeSH
- nefrektomie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- kabozantinib,
- MeSH
- analýza přežití MeSH
- anilidy farmakologie terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- karcinom z renálních buněk farmakoterapie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory ledvin * farmakoterapie MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- pyridiny farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- tyrosinkinasové receptory farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
