PURPOSE: The aim of the study is to capture the difference between the groups in direct relation to the type of electrode array insertion during cochlear implantation (CI). The robotic insertion is expected to be a more gently option. As recent studies have shown, there is a difference in perception of visual vertical (SVV) and postural control related to the CI. We assume that there can be differences in postural control and space perception outcomes depending on the type of the surgical method. METHODS: In total, 37 (24 females, mean age ± SD was 42.9 ± 13.0) candidates for CI underwent an assessment. In 14 cases, the insertion of the electrode array was performed by a robotic system (RobOtol, Colin, France) and 23 were performed conventionally. In all of these patients, we performed the same examination before the surgery, the first day, and 3 weeks after the surgery. The protocol consists of static posturography and perception of visual vertical. RESULTS: The both groups, RobOtol and conventional, responded to the procedure similarly despite the dissimilar electrode insertion. There was no difference between two groups in the dynamic of perception SVV and postural parameters. Patients in both groups were statistically significantly affected by the surgical procedure, SVV deviation appeared in the opposite direction from the implanted ear: 0.90° ± 1.25; - 1.67° ± 3.05 and - 0.19° ± 1.78 PRE and POST surgery (p < 0.001). And this deviation was spontaneously adjusted in FOLLOW-UP after 3 weeks (p < 0.01) in the both groups. We did not find a significant difference in postural parameters between the RobOtol and conventional group, even over time. CONCLUSION: Although the robotic system RobOtol allows a substantial reduction in the speed of insertion of the electrode array into the inner ear, our data did not demonstrate a postoperative effect on vestibular functions (SVV and posturography), which have the same character and dynamics as in the group with standard manual insertion. REGISTRATION NUMBER: The project is registered on clinicaltrials.gov (registration number: NCT05547113).
- MeSH
- dospělí MeSH
- kochleární implantace * metody MeSH
- kochleární implantáty MeSH
- lidé středního věku MeSH
- lidé MeSH
- posturální rovnováha * fyziologie MeSH
- roboticky asistované výkony * metody MeSH
- vnímání prostoru * fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, which are mostly benign in nature. Amongst all genes, Succinate Dehydrogenase Subunit D (SDHD) is the most commonly mutated in familial HNPGLs. In about 30% of HNPGLs, germline mutations in SDHD can also occur in the absence of positive family history, thus giving rise to "occult familial" cases. Our aim was to evaluate the pattern of SDHD germline mutations in Czech patients with HNPGLs. MATERIALS AND METHODS: We analyzed a total of 105 patients with HNPGLs from the Otorhinolaryngology departments of 2 tertiary centers between 2006 - 2021. All underwent complex diagnostic work-up and were also consented for genetic analysis. RESULTS: Eighty patients aged 13-76 years were included; around 60% with multiple PGLs were males. Carotid body tumor was the most frequently diagnosed tumor. Germline SDHD mutation was found in only 12% of the Czech patients; approximately 78% of those harboring the mutation had negative family history. The mutation traits had higher affiliation for multiple tumors with nearly 70% patients of ≤ 40 years of age. CONCLUSION: An SDHD mutation variant was shared amongst unrelated patients but no founder-effect was established. Our findings confirmed that the pattern of SDHD mutation distribution amongst HNPGLs in Czech Republic differs from most studies worldwide.
- MeSH
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nechromafinní paragangliom * MeSH
- paragangliom * epidemiologie genetika diagnóza MeSH
- senioři MeSH
- sukcinátdehydrogenasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Nano-sized carriers are widely studied as suitable candidates for the advanced delivery of various bioactive molecules such as drugs and diagnostics. Herein, the development of long-circulating stimuli-responsive polymer nanoprobes tailored for the fluorescently-guided surgery of solid tumors is reported. Nanoprobes are designed as long-circulating nanosystems preferably accumulated in solid tumors due to the Enhanced permeability and retention effect, so they act as a tumor microenvironment-sensitive activatable diagnostic. This study designs polymer probes differing in the structure of the spacer between the polymer carrier and Cy7 by employing pH-sensitive spacers, oligopeptide spacers susceptible to cathepsin B-catalyzed enzymatic hydrolysis, and non-degradable control spacer. Increased accumulation of the nanoprobes in the tumor tissue coupled with stimuli-sensitive release behavior and subsequent activation of the fluorescent signal upon dye release facilitated favorable tumor-to-background ratio, a key feature for fluorescence-guided surgery. The probes show excellent diagnostic potential for the surgical removal of intraperitoneal metastasis and orthotopic head and neck tumors with very high efficacy and accuracy. In addition, the combination of macroscopic resection followed by fluorescence-guided surgery using developed probes enable the identification and resection of most of the CAL33 intraperitoneal metastases with total tumor burden reduced to 97.2%.
- MeSH
- chytré polymery * MeSH
- fluorescence MeSH
- fluorescenční barviva chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- nádory hlavy a krku * diagnostické zobrazování chirurgie MeSH
- polymery MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Cochlear implantation (CI) is associated with changes in the histopathology of the inner ear and impairment of vestibular function. OBJECTIVE: The objectives of our study were to evaluate patients for clinical manifestations of space perception and balance changes before surgery, compare them with asymptomatic subjects (controls), and report changes in posturography and subjective visual vertical (SVV) during the acute post-surgery period in patients. METHODS: Examination was performed using static posturography and the SVV measurement. We examined 46 control subjects and 39 CI patients. Patients were examined pre-surgery (Pre), 2nd day (D2) and then 14th day (D14) after implantation. RESULTS: Baseline SVV was not different between patients and control group. There was a statistically significant difference (p < 0.001) in SVV between subgroups of right- and left-implanted patients at D2 (-1.36±3.02° and 2.71±2.36°, right and left side implanted respectively) but not Pre (0.76±1.07° and 0.31±1.82°) or D14 (0.72±1.83° and 1.29±1.60°). Baseline posturography parameters between patients and control group were statistically significantly different during stance on foam with eyes closed (p < 0.05). There was no statistically significant difference in posturography among Pre, D2 and D14. CONCLUSIONS: CI candidates have impaired postural control before surgery. CI surgery influences perception of subjective visual vertical in acute post-surgery period with SVV deviation contralateral to side of cochlear implantation, but not after two weeks.
- MeSH
- kochleární implantace * MeSH
- lidé MeSH
- posturální rovnováha MeSH
- vestibulární aparát * MeSH
- vnímání prostoru MeSH
- zraková percepce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. METHODS: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. RESULTS: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. CONCLUSION: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC.
- MeSH
- lidé MeSH
- nádory ucha * patologie MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom * patologie MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- zvukovod patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Chirurgická a ambulantní péče o pacienta s ušním onemocněním je nedílnou součástí otorinolaryngologie. Zahrnuje široké spektrum výkonů v oblasti zevního zvukovodu, středouší a dalších částí pyramidy s rozličnými indikacemi. Objektivní nárůst počtu ušních výkonů na pracovišti autorů vedl k myšlence zmapování situace ušní operativy v České republice. Sběr dat proběhl dotazníkovou formou od ledna 2020 do srpna 2020, kontaktováni byli vedoucí pracovišť všech lůžkových ORL pracovišť v České republice. Výtěžnost dotazníku byla 100 %. Ze všech lůžkových ORL pracovišť v České republice provádí ušní operace 80 %, z nich téměř 85 % pracovišť provádí operace taktéž u dětských pacientů. Maximum ušní operativy se odehrává na půdě fakultních klinik, kde je v posledních 10 letech patrný nárůst počtu odoperovaných pacientů. Zde se taktéž centralizují specializované výkony typu kochleární implantace a rozsáhlejší výkony na temporální kosti.
Surgical and outpatient care of a patient with ear disease is an integral part of otorhinolaryngology. It includes a wide range of procedures in the region of the external auditory canal, middle ear and other parts of the pyramid bone with various indications. The objective increase in the number of ear procedures at the department of the authors was the impulse to map the situation of ear surgery in the Czech Republic. Data were collected in the period from January 2020 to August 2020, using a questionnaire, which was sent to the heads of all ENT departments in the Czech Republic. The yield of the questionnaire was 100%. Overall 80% of all ENT departments perform ear surgeries, of which almost 85% perform pediatric ear surgeries too. The maximum of ear surgery proceeds in the university departments where an increase in the number of operated patients has been observed in the last 10 years. These departments also cover specialized procedures such as cochlear implantations and more extensive surgeries on the temporal bone.
- MeSH
- ambulantní péče MeSH
- lidé MeSH
- nemoci ucha * chirurgie terapie MeSH
- nemocniční oddělení MeSH
- otologické chirurgické výkony * MeSH
- poruchy sluchu chirurgie terapie MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
Karcinomy hlavy a krku tvoří prognosticky nepříznivou skupinu onemocnění zatíženou jak vysokou mortalitou, tak i morbiditou způsobenou klasickými léčebnými postupy, jako je chirurgie, radioterapie a chemoterapie. Tyto nádory však patří mezi onemocnění s početným zastoupením imunitních buněk, které je ještě umocněno u tumorů indukovaných HPV, a jsou tak velmi perspektivním cílem imunoterapeutických postupů. Imunoterapie za využití blokátorů kontrolních bodů imunitního systému se v posledních letech stala jedním z pilířů onkologické terapie, kterou lze aplikovat již v 1. linii léčby u rekurentního a metastatického karcinomu hlavy a krku. Na tuto léčbu ale překvapivě reaguje pouze malá část pacientů. Podrobná analýza imunitního infiltrátu v nádorovém mikroprostředí je pak jedním z klíčů ke zlepšení léčebných výsledků a k efektivnější stratifikaci pacientů, kteří mohou z aplikace imunoterapie a zmírnění klasické terapie profitovat.
Head and neck cancer is prognostically unfavourable group of diseases burdened by high mortality and morbidity following classic treatment regimens, such as surgery, radiotherapy and chemotherapy. Nevertheless, these tumors are highly infiltrated by immune cells, especially in case of HPV induced tumors, and constitute a perspective target for immune-based treatment. Immunotherapy with checkpoint inhibitors has become one of the basic pillars of cancer therapy, that is applicable as a first line treatment in recurrent and metastatic head and neck cancer. However, only a small fraction of patients is responsive to the therapy. In-depth analysis of immune cells in the tumor microenvironment could be the key element for improvement of current treatment regimens and effective stratification of patients that could benefit from immunotherapy and de-intensification of classic therapeutic protocols.
- Klíčová slova
- tumor-infiltrující leukocyty,
- MeSH
- imunoterapie MeSH
- infekce papilomavirem MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory hlavy a krku * imunologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Plasmacytoid dendritic cells (pDCs) are the most potent type I interferon-producing cells and play an important role in antiviral immunity. Tumor-infiltrating pDCs were shown to be predominantly pro-tumorigenic, with reduced ability to produce interferon alpha (IFNα) and confirmed capacity to prime regulatory T cells (Tregs) by the ICOS/ICOS-L pathway. Because a significant number of HNSCCs are induced by human papillomaviruses and show markedly different immune profiles than non-virally induced tumors, we compared the phenotype and functional capacity of HNSCC-infiltrating pDCs to the HPV status of the tumor. We observed a reduced capacity of pDCs to produce IFNα upon toll-like receptor activation in HPV-negative samples and a rather uncompromised functionality in HPV-associated tumors. Additionally, supernatants from non-virally induced but not HPV-associated tumor cell suspensions significantly inhibited IFNα production by peripheral blood-derived pDCs. We identified IL-10 and TNFα as the soluble pDC-suppressive factors with the highest variability between HPV-negative and HPV-positive tumor-derived supernatants. Additionally, we observed a positive correlation of tumor-infiltrating pDCs with Tregs in HPV-negative samples but not in virally induced tumors. Overall, our study indicates that the immunosuppressive cytokine milieu rich in IL-10 and TNFα in HPV-negative but not in HPV-positive HNSCC significantly affects the functional capacity of tumor-infiltrating pDCs, and such dysfunctional pDCs may further support the immunosuppressive tumor microenvironment by promoting the expansion of Tregs in the tumor tissue.
- MeSH
- biologické markery MeSH
- cytokiny metabolismus MeSH
- dendritické buňky imunologie metabolismus patologie MeSH
- dlaždicobuněčné karcinomy hlavy a krku etiologie metabolismus patologie MeSH
- exprese genu MeSH
- infekce papilomavirem komplikace virologie MeSH
- interferon alfa imunologie metabolismus MeSH
- lidé MeSH
- náchylnost k nemoci MeSH
- nádorové mikroprostředí * imunologie MeSH
- regulační T-lymfocyty imunologie metabolismus MeSH
- studie případů a kontrol MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- virová transformace buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH