Lyme disease, a tick-borne illness caused by Borrelia spirochetes, poses a significant threat to public health. While acaricides effectively control ticks on pets and livestock, their impact on pathogen transmission is often unclear. This study investigated the acaricidal efficacy of fipronil against Ixodes ricinus ticks and its potential to block Borrelia afzelii transmission. Initially, we employed the ex vivo membrane blood-feeding system to assess the dose–response acaricidal activity of ivermectin, fipronil and its metabolite fipronil sulfone, when supplemented in the blood meal throughout tick feeding. To obtain the temporal resolution of their acaricidal activity, ticks were allowed to initiate blood feeding on an artificial membrane before being exposed to a 1-time topical application of these acaricides. Fipronil demonstrated superior speed of acaricidal activity, with onset of tick moribundity within a few hours, prompting its selection for further in vivo testing with Borrelia-infected ticks. The I. ricinus nymphs infected with B. afzelii were topically treated with fipronil shortly after attachment to mice. Four weeks post-feeding, the skin and internal organs were examined for the presence of Borrelia. No spirochetes were detected in any organ of mice exposed to fipronil-treated ticks, while 9 out of 10 control mice, exposed to non-treated infectious ticks, displayed Borrelia infection. The in vitro co-culture experiments confirmed that fipronil had no direct effect on Borrelia viability, indicating a tick-directed effect. Overall, these results underline the potential of fipronil as a valuable tool for tick control strategies and suggest a concept for acaricide-mediated Borrelia-transmission blockers.

• Klíčová slova
• Borrelia afzelii, Ixodes ricinus, Lyme disease, acaricide, ex vivo membrane blood feeding, fipronil, ivermectin, spirochetes, ticks,
• MeSH
• akaricidy * farmakologie   MeSH
• Borrelia burgdorferi komplex * účinky léků   fyziologie   MeSH
• klíště * mikrobiologie   účinky léků   MeSH
• lymeská nemoc * přenos   prevence a kontrola   mikrobiologie   MeSH
• myši MeSH
• nymfa mikrobiologie   účinky léků   MeSH
• pyrazoly * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akaricidy * MeSH
• fipronil MeSH Prohlížeč
• pyrazoly * MeSH

BACKGROUND: We present a series of papillary renal cell carcinomas (PRCC) reminiscent of so-called "oncocytic variant of papillary renal cell carcinoma" (OPRCC), included in the 2016 WHO classification as a potential type 3 PRCC. OPRCC is a poorly understood entity, cytologically characterized by oncocytic cells with non-overlapping low grade nuclei. OPRCC is not genotypically distinct and the studies concerning this variant have shown an inconsistent genetic profile. The tumors presented herein demonstrated predominantly papillary/tubulopapillary architecture and differed from OPRCC by pseudostratification and grade 2-3 nuclei (Fuhrman/ISUP). Because there is a morphologic overlap between renal oncocytoma (RO) and PRCC in the cases included in this study, the most frequently affected chromosomes in RO and PRCC were analyzed. MATERIALS AND METHODS: 147 PRCC composed of oncocytic cells were retrieved from our registry in order to select a group of morphologically uniform tumors. 10 cases with predominantly papillary, tubulopapillary or solid architectural patterns were identified. For immunohistochemical analysis, the following antibodies were used: vimentin, antimitochondrial antigene (MIA), AMACR, PAX8, CK7, CK20, AE1-3, CAM5.2, OSCAR, Cathepsin K, HMB45, SDHB, CD10, and CD117. Enumeration changes of locus 1p36, chromosomes 7, 14, 17, X, Y and rearrangement of CCND1 were examined by FISH. For further study, only tumors showing karyotype similar to that of RO were selected. The tumors exhibiting either trisomy of chromosomes 7, 17 or gain of Y, thus abnormalities characteristic for PRCC, were excluded. RESULTS: There were 5 males and 5 females, with patient age ranging from 56 to 79 years (mean 66.8 years). The tumor size ranged from 2 to 10 cm (mean 5.1 cm). Follow-up was available for 8/10 patients (mean 5.2 years); one patient died of the disease, while 7 of 8 are alive and well. Immunohistochemically, all cases were reactive for AMACR, vimentin, PAX8, OSCAR, CAM5.2, and MIA. SDHB was retained in all cases. 9/10 cases were positive for CD10, 7/10 cases reacted with CK7, 4/10 with Cathepsin K, and 2/10 with AE1-3. None of the cases were positive for CD117, HMB45 and CK20. All 10 cases were analyzable by FISH and showed chromosomal abnormalities similar to that usually seen in RO (i.e. loss of 1p36 gene loci, loss of chromosome Y, rearrangement of CCND1 and numerical changes of chromosome 14). CONCLUSIONS: We analyzed a series of renal tumors combining the features of PRCC/OPRCC and RO, that included pseudostratification and mostly high grade oncocytic cells lining papillary/tubulopapillary structures, karyotype characterized by loss of 1p36, loss of chromosome Y, rearrangement of CCND1 gene and numerical changes of chromosome 14. Despite the chromosomal numerical abnormalities typical of RO, we classified these tumors as part of the spectrum of PRCC because of their predominant papillary/tubulopapillary architecture, immunoprofile that included reactivity for AMACR, vimentin and lack of reactivity for CD117, all of which is incompatible with the diagnosis of RO. This study expands the morphological spectrum of PRCC by adding a cohort of diagnostically challenging cases, which may be potentially aggressive.

• Klíčová slova
• Chromosomal aberration pattern, FISH, High grade, Kidney, Oncocytic, Oncocytoma, Papillary renal cell carcinoma,
• MeSH
• chromozomální aberace MeSH
• diferenciální diagnóza MeSH
• karcinom z renálních buněk genetika   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory ledvin genetika   metabolismus   patologie   MeSH
• oxyfilní adenom genetika   metabolismus   patologie   MeSH
• papilární karcinom genetika   metabolismus   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH

Emperipolesis has recently been described as a constant feature of "biphasic squamoid" papillary renal cell carcinoma (BPRCC). We also noticed this in some high-grade (HG) RCC, which promoted the present study to estimate the incidence of emperipolesis in RCCs and to describe them in further detail. 14 cases of HGRCC showing emperipolesis were retrieved from our registry. Microscopic examination of filed slides was supplemented with immunohistochemical and molecular-genetic analyses using paraffin embedded tissue. 12 of 14 patients were males with a mean age of 58.6 years (range 41-72 years). Tumor size ranged from 6-16.5 cm (mean of 8.8 cm). Follow up data were available for 8/14 patients (range 0.5-10 years). Metastases were documented in 6 cases. All tumors showed solid-alveolar growth patterns with focal pseudopapillary features, and were composed of large cells with bizarre nuclei and eosinophilic rhabdoid-like cytoplasm. Emperipolesis was a constant and prominent feature in large bizarre cells. All cases were positive for OSCAR, CANH 9, vimentin, cyclin D1, INI-1, and myoD1, while negative for melanocytic markers, CK 7, myoglobin, cathepsin K, and TFE3. VHL gene abnormalities were found in 6/9 analyzable cases, of which 2 demonstrated polysomy of chromosomes 7, 17. Emperipolesis is a rare histomorphologic feature which can be seen not only in BPRCCs but also in highgrade CCRCCs. All RCC cases with prominent emperipolesis fulfilled both morphologic and immunohistochemical diagnostic criteria of high-grade CCRCC. The majority of patients with available follow up information developed metastases.

• MeSH
• dospělí MeSH
• emperipoléza * MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory ledvin genetika   patologie   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
• Názvy látek
• nádorové biomarkery MeSH

AIM: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. MATERIALS & METHODS: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. RESULTS: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. CONCLUSION: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

• Klíčová slova
• anti-EGFR, mCRC, metastatic colorectal cancer, prevalence, real world,
• MeSH
• exony MeSH
• kolorektální nádory epidemiologie   mortalita   patologie   MeSH
• lidé MeSH
• míra přežití MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• prevalence MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny B-Raf MeSH
• protoonkogenní proteiny p21(ras) MeSH

Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.

• Klíčová slova
• Cystic, Kidney, Molecular genetics, Necrosis, Necrotics, Papillary renal cell carcinoma,
• MeSH
• chromozomální aberace MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční metody   MeSH
• imunohistochemie metody   MeSH
• karcinom z renálních buněk diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární patologie metody   MeSH
• nádorové biomarkery analýza   MeSH
• nádory ledvin diagnóza   patologie   MeSH
• papilární karcinom diagnóza   patologie   MeSH
• prognóza 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
• Názvy látek
• nádorové biomarkery MeSH

Sodium polystyrene sulphonate (Resonium A) in sorbitol given as an enema or orally to treat hyperkalaemia has been described to induce intestinal necrosis in uraemic patients. We report a case of a premature infant with acute renal insufficiency who developed focal transmural necrosis and perforation of the small intestine after 10 days of administration of calcium polystyrene sulphonatum (Calcium Resonium) in sorbitol by enema and by nasogastric tube. On histological examination of the resected part of the small intestine, numerous strongly basophilic angular crystals of resonium were found in the lumen, in the necrotic wall, as well as in the organized exudate on the peritoneal surface. The crystals showed a strong direct Schiff positivity without preoxidation. They were also stained using PAS, Giemsa, Ziehl-Neelsen, Schmorl, and Gram method. In contrast, the crystals were Congo red and Alcian blue (pH 2.5) negative and non-birefringent. The direct Schiff positivity without preoxidation is virtually pathognomonic for resin crystals in routinely processed tissues. The same crystals were observed in the lumen of the small intestine and in peritoneal adhesions at autopsy. Thus our case provides additional evidence that Resonium A/Calcium Resonium in sorbitol administered as an enema or orally can lead to intestinal necrosis in uraemic patients.

• MeSH
• gastrointestinální intubace MeSH
• klyzma MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• nekróza MeSH
• nemoci nedonošenců farmakoterapie   MeSH
• novorozenec MeSH
• osmotická diuretika aplikace a dávkování   škodlivé účinky   MeSH
• perforace střeva chemicky indukované   patologie   MeSH
• polystyreny aplikace a dávkování   škodlivé účinky   MeSH
• sorbitol aplikace a dávkování   škodlivé účinky   MeSH
• tenké střevo účinky léků   patologie   MeSH
• uremie farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• osmotická diuretika MeSH
• polystyrene sulfonic acid MeSH Prohlížeč
• polystyreny MeSH
• sorbitol MeSH