SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

• MeSH
• antivirové látky škodlivé účinky   MeSH
• cytomegalovirové infekce * epidemiologie   MeSH
• Cytomegalovirus genetika   MeSH
• lidé MeSH
• neutropenie * chemicky indukované   komplikace   MeSH
• příjemce transplantátu MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• valganciklovir škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Pathogenic germline mutations c.1100delC and p.I157T in the CHEK2 gene have been associated with increased risk of breast, colon, kidney, prostate, and thyroid cancers; however, no associations have yet been identified between these two most common European founder mutations of the CHEK2 gene and ovarian cancers of any type. Our review of 78 female heterozygous carriers of these mutations (age > 18 years) found strikingly higher proportion of adult-type granulosa cell tumors of the ovary (AGCTs) among ovarian cancers that developed in these women (~36%) compared to women from the general population (1.3%). Based on this finding, we performed a cross-sectional study that included 93 cases previously diagnosed with granulosa cell tumors, refined and validated their AGCT diagnosis through an IHC study, determined their status for the two CHEK2 mutations, and compared the prevalence of these mutations in the AGCT cases and reference populations. The prevalence ratios for the p.I157T mutation in the AGCT group relative to the global (PR = 26.52; CI95: 12.55-56.03) and European non-Finnish populations (PR = 24.55; CI95: 11.60-51.97) support an association between the CHEK2p.I157T mutation and AGCTs. These rare gynecologic tumors have not been previously associated with known risk factors and genetic predispositions. Furthermore, our results support the importance of the determination of the FOXL2p.C134W somatic mutation for accurate diagnosis of AGCTs and suggest a combination of IHC markers that can serve as a surrogate diagnostic marker to infer the mutational status of this FOXL2 allele.

• Publikační typ
• časopisecké články MeSH

Carney triad is a multitumor syndrome affecting almost exclusively young women in a nonfamilial setting, which manifests by multifocal gastric gastrointestinal stromal tumors, paragangliomas, and pulmonary chondroma. The Carney triad-associated tumors are characterized by a deficiency of the mitochondrial succinate dehydrogenase enzymatic complex. Recently, it has been observed that the deficiency results from epigenetic silencing of the SDHC gene by its promoter hypermethylation. To elucidate anatomic distribution of SDHC promoter methylation in Carney triad patients and thus to shed some light on the possible natural development of this epigenetic change, both neoplastic and available non-neoplastic tissues of 3 patients with Carney triad were tested for hypermethylation at the SDHC promoter site. SDHC promoter hypermethylation was proven in all tumors studied. Lack of SDHC epigenetic silencing in the non-neoplastic lymphoid and duodenal tissue (ie, tissues not involved in the development of Carney triad-associated tumors) together with the finding of SDHC promoter hypermethylation in the non-neoplastic gastric wall favors the hypothesis of postzygotic somatic mosaicism as the biological background of Carney triad; it also offers an explanation of the multifocality of gastrointestinal stromal tumors of the stomach occurring in this scenario as well. However, the precise mechanism responsible for the peculiar organ-specific distribution of Carney triad-associated tumors is still unknown.

• MeSH
• chondrom * genetika   metabolismus   patologie   MeSH
• DNA nádorová * genetika   metabolismus   MeSH
• leiomyosarkom * genetika   metabolismus   patologie   MeSH
• lidé MeSH
• membránové proteiny * genetika   metabolismus   MeSH
• metylace DNA * MeSH
• mozaicismus * MeSH
• nádorové proteiny * genetika   metabolismus   MeSH
• nádory plic * genetika   metabolismus   patologie   MeSH
• nádory žaludku * genetika   metabolismus   patologie   MeSH
• nechromafinní paragangliom * genetika   metabolismus   patologie   MeSH
• promotorové oblasti (genetika) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Undifferentiated (sarcomatoid) carcinomas may closely mimic gastrointestinal stromal tumors (GISTs) due to possible histological and immunohistochemical overlap between these two entities. To avoid unnecessary employment of a wide spectrum of immunohistochemical stainings and molecular genetics and thus decrease costs, finding simple morphological features to target further investigation of such neoplasms of the gastrointestinal tract would be helpful. Five cases classified as undifferentiated (sarcomatoid) carcinomas with a definite proof of the diagnosis, i. e. the presence of a differentiated carcinomatous component, were retrieved from archives of several institutions. For comparison, 84 cases of GIST mutated in KIT or PDGFRA genes served as the control group. Hematoxylin and eosin stained slides were evaluated for the presence of patterns which might discriminate between sarcomatoid carcinoma and GIST. Lymphatic invasion and entrapment of fat tissue strongly favor the diagnosis of undifferentiated carcinoma, as it was found in all or almost all cases of undifferentiated carcinoma, but in no GIST. Alternation of low- and high- grade areas, formation of angiosarcomatous-like spaces, and the presence of yolk sac-like areas were also detected in all cases of undifferentiated carcinoma, but only in 1.2%, 2.4% and 7.2% of the GISTs, respectively. Furthermore, DOG1 was negative in all cases of undifferentiated carcinoma. According to this study, the presence of the histological findings listed above should prompt extensive tumor sampling in order to find a differentiated carcinomatous component. However, due to the small number of cases of undifferentiated carcinoma available for the study, a larger multi-institutional study is warranted.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• gastrointestinální nádory diagnóza   patologie   MeSH
• gastrointestinální stromální tumory diagnóza   patologie   MeSH
• karcinom diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Nové perspektivní jednotky: nádory ledvin popsané v době po WHO histopatologické klasifikaci z roku 2016. Histopatologická klasifikace renálních tumorů je každým rokem komplikovanější. Nové perspektivní nádorové jednotky jsou definovány nejen na podkladě morfologických a imunohistochemických vlastností, ale častěji na základě molekulárně genetických vlastností. V tomto přehledném článku představujeme nové jednotky, které mají jasně definován genetický podklad. V současnosti jsou popisovány nádory s postiženou mTOR drahou. Jde o eosinofilní solidní a cystický renální karcinom, "high‑grade“ onkocytický tumor a "low‑grade“ onkocytický tumor. Všechny tyto podtypy, přes přítomnost "high‑grade“ cytologických vlastností se chovají indolentně. Další jsou MiTF renální (translokační) karcinomy, které jsou zařazeny do WHO klasifikací od roku 2004. Nově se ale rozpoznává renální karcinom s amplifikací TFEB genu. Jde o léze agresivní (oproti TFEB translokovaným renálním karcinomům) a jsou bez molekulární genetiky obtížně diagnostikovatelné. Dále jsou zmíněny další intenzivně studované jednotky nádorů ledvin. Jejich současné postavení vzhledem k oficiální WHO klasifikaci zůstává nejasné. Přes rychlý pokrok v diagnostice renálních nádorů se zdá, že využití těchto poznatků v rutinní klinické praxi bude limitované (rok 2020). Závěr: Urologové a onkologové musí v brzké době očekávat novou poměrně složitou klasifikaci nádorů ledvin založenou z části na mole‑ kulárně genetickém vyšetření. Dalším krokem by měla být personalizace léčby, k tomu však klinikům zatím chybí vhodné portfolio léčebných možností zejména u systémové léčby.

Histopathological Classification of renal tumors is more complicated every year. New emerging entities are defined not only by morphology and immunohistochemical profile, but also more frequently using molecular genetic techniques. In this review, new perspective entities with clearly defined molecular‑genetic background are introduced. Groups of renal tumors sharing abnor‑ malities in the mTOR pathway were recognized recently. It is eosinophilic solid and cystic renal cell carcinoma, high grade oncocytic tumor, and low grade oncocytic tumor. All subtypes follow an indolent non aggressive course despite presence of high‑grade nuclei. MitF related renal cell carcinomas (translocation) renal cell carcinomas were listed in WHO classification since 2004. New member of RCC with impaired TFEB gene is renal cell carcinoma with TFEB amplification. This subtype is aggressive (contrary to TFEB translocated RCC) and very difficult to diagnose. Several other entities are intensively studied and examined. Their current status is questionable and more likely they will not be listed in upcoming WHO classification. Despite the rapid progression in diagnostic abilities, practical impact for routine clinical practice is (in 2020) limited. Conclusions: Urologists and oncologists should expect new, relatively complicated classification of renal tumors, partly based on molecular genetic features. However, a more personalized approach to individual patients is desirable, clinical specialists do not dispose appropriate spectrum of systemic treatment modalities.

• MeSH
• diagnostické techniky molekulární MeSH
• karcinom z renálních buněk * genetika   klasifikace   MeSH
• lidé MeSH
• nádory ledvin * genetika   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Předkládáme případ naší dlouhodobě sledované pacientky s radikálně resekovaným, IDH mutovaným glioblastomem s primitivní neuronální komponentou, která s pouze mírnými neurologickými komplikacemi žije již 9 let od stanovení diagnózy, se zachovalou velmi dobrou kvalitou života. Radikalita chirurgické resekce spolu s mutacemi IDH genů představují prognosticky příznivé faktory u high grade gliových nádorů centrální nervové soustavy.

We present a case of long-term followed-up patient with radically resected IDH mutant glioblastoma with a primitive neuronal component who has survived for 9 years with only moderate neurological complications and with a very good quality of life. Radicality of surgical resection together with mutations of the IDH genes are prognostically favourable factors in high grade glial neoplasms of the central nervous system.

• MeSH
• antikonvulziva aplikace a dávkování   farmakologie   MeSH
• chemoradioterapie metody   MeSH
• edém mozku farmakoterapie   prevence a kontrola   MeSH
• glioblastom chirurgie   patologie   radioterapie   MeSH
• karbamazepin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mozku * genetika   chirurgie   patologie   MeSH
• primitivní neuroektodermové nádory chirurgie   patologie   radioterapie   MeSH
• temozolomid aplikace a dávkování   farmakologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND/AIM: The aim of our study was to assess the predictive role of primary tumour sidedness (PTS) in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS and treated with targeted agents. PATIENTS AND METHODS: The cohort included 178 patients treated with first-line chemotherapy plus cetuximab, panitumumab or bevacizumab. RESULTS: We observed longer progression-free survival (PFS) and overall survival (OS) in patients with left-sided (L-CRC) compared to right-sided tumours (R-CRC) treated with anti-EGFR mAbs (p=0.0033 and p=0.0037), while there was no difference in patients treated with bevacizumab (p=0.076 and p=0.56). Finally, we observed longer PFS and OS in patients with L-CRC treated with anti-EGFR mAbs and those with R-CRC treated with bevacizumab compared to the reverse combination (p=0.0002 and p=0.011). CONCLUSION: PTS is a predictive factor for anti-EGFR mAbs, not for bevacizumab. Superior survival was observed when anti-EGFR mAbs were used for L-CRC and bevacizumab for R-CRC.

• MeSH
• bevacizumab aplikace a dávkování   MeSH
• cetuximab aplikace a dávkování   MeSH
• erbB receptory genetika   MeSH
• geny ras genetika   MeSH
• kolorektální nádory farmakoterapie   genetika   patologie   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• nádory rekta farmakoterapie   patologie   MeSH
• nádory tračníku farmakoterapie   patologie   MeSH
• panitumumab aplikace a dávkování   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The measurement of serum tumour markers is a simple and non-invasive method for assessing the response to systemic therapies in metastatic colorectal cancer (mCRC) and estimation of prognosis. The aim of our retrospective study was to evaluate the association of baseline serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) with outcome of patients with mCRC treated with combination of chemotherapy and monoclonal antibodies against epidermal growth factor receptor (anti-EGFR mAbs) in the first line. In our study, the cohort included 102 patients treated with therapy based on anti-EGFR mAbs between years 2011 and 2017 at Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Czech Republic. Serum samples were collected within one month before the initiation of treatment. In multivariate Cox analysis that included serum tumour markers and clinical baseline parameters show that high baseline serum CA 19-9 was significantly associated with worse progression-free survival (HR=1.871, p=0.0330) and also overall survival (HR=3.903, p=0.0006). We have not demonstrated association of baseline levels of CEA, TK and TPS with patients' outcome. CA 19-9 is commonly used serum tumour marker which is simple and readily available and its candidate prognostic importance in the setting of anti-EGFR therapy deserves to be studied in prospective trials.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Recently, we came with the theory of a possible relationship between a group of testicular and pancreatic tumors. We used one case of a pancreatic analogue solid pseudopapillary neoplasm of the testis composed partially of areas reminiscent of solid pseudopapillary neoplasm (SPN) of the pancreas and partially of structures identical to primary signet ring stromal tumor of the testis (PSRSTT) as a connecting link between these two entities. After demonstrating that PSRSTT and pancreatic analogue SPN of the testis share the same immunoprofile and genetic features characteristic for pancreatic SPN, we came to the conclusion that pancreatic analogue SPN of the testis and PSRSTT represent a morphological spectrum of a single entity and that both are related to the pancreatic SPN. DESIGN: The aim of this study is to present a series of 6 cases of testicular tumors, which lacked the signet ring cell component and were thus morphologically very similar to the SPN of the pancreas. The goal of this study is to compare the genetic background of these testicular tumors that are obviously related to the PSRSTT/pancreatic analogue SPN of the testis with the series of 8 pancreatic SPN. RESULTS: The mutational analysis revealed an oncogenic somatic mutation in the exon 3 of the CTNNB1 (β-catenin) gene in all analyzable (5/6) testicular and all pancreatic (8/8) tumors. The immunoprofile (positivity with β-catenin, CD10, vimentin, NSE, CD56, and negativity with inhibin, calretinin, chromogranin) was identical in all testicular and pancreatic tumors. CONCLUSION: This study expanded the morphological spectrum of the PSRSTT/pancreatic analogue SPN of the testis by adding 6 cases without the signet ring cell component. Considering the obvious analogy of PSRSTT/pancreatic analogue SPN of the testis/SPN of the testis and their relationship to the pancreatic SPN we propose the collective term "solid pseudopapillary neoplasm of the testis" for these tumors. The mutational profile of the SPN of the testis and pancreas was the same in both groups of tumors which we consider as a final proof that SPN of the testis is identical to the SPN of the pancreas.

• MeSH
• beta-katenin genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery MeSH
• nádory slinivky břišní genetika   patologie   MeSH
• pankreas patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testikulární nádory genetika   patologie   MeSH
• testis patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Primary signet ring stromal tumor of the testis (PSRSTT) is an extremely rare tumor described only twice in the literature. Pancreatic-analogue solid pseudopapillary neoplasm (SPN) of the testis is a recently reported entity with morphological overlap with PSRSTT. We reviewed our files to find all cases of PSRSTT to better characterize this entity. We studied 13 cases of PSRSTTs using histological, immunohistochemical (IHC), and molecular genetic methods and compared the results with pancreatic SPN. Grossly, the size of PSRSTTs ranged from 0.5 to 2 cm (mean 1.1). Microscopically, PSRSTTs predominantly showed a proliferation of low-grade epithelioid cells containing characteristic cytoplasmic vacuole dislodging the nucleus (signet ring cells) separated by fibrous septa into trabeculae and nests. The immunoprofile was characterized by immunoreactivity for β-catenin, cyclin D1 (nuclear positivity for both antibodies), CD10, vimentin, galectin-3, claudin 7, α-1-antitrypsin, CD56, and neuron-specific enolase and negativity for chromogranin, inhibin, calretinin, SF-1, NANOG, OCT3/4, and SALL4. In some cases, the IHC panel was restricted because of a limited amount of tissue. Molecular genetic analysis revealed mutations within exon 3 of the CTNNB1 encoding β-catenin in all analyzable cases. Based on histological similarities between pancreatic SPN and PSRSTT and their identical IHC and molecular genetic features, we assume that both neoplasms share the same pathogenesis, and thus, PSRSTT can be considered as a testicular analogue of pancreatic SPN.

• MeSH
• beta-katenin analýza   genetika   MeSH
• biopsie MeSH
• buněčná diferenciace MeSH
• buněčný rodokmen MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• gonadální stromální nádory * chemie   genetika   imunologie   patologie   MeSH
• imunohistochemie MeSH
• karcinom z prstenčitých buněk * chemie   genetika   imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory slinivky břišní * chemie   genetika   imunologie   patologie   MeSH
• proliferace buněk MeSH
• stupeň nádoru MeSH
• testikulární nádory * chemie   genetika   imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH