Quality of life in patients after vestibular schwannoma surgery.

AIM: To evaluate the most important factors of quality of life in patients after vestibular schwannoma surgery. MATERIALS AND METHODS: Patients with unilateral sporadic occurrence of vestibular schwannoma who underwent surgery via suboccipital-retrosigmoid approach were included in the prospective study (2018-2021). Patients after previous Leksell gamma knife irradiation (or other methods of stereotactic radiosurgery) were excluded. Quality of life was assessed using 10 validated questionnaires that were distributed preoperatively, 3 months and 1 year after the surgery. RESULTS: A total of 76 patients were included in the study, complete data were analysed in 43 of them (response rate 57%). Grade III and IV represented up to 70% of all tumors. Patients with larger tumors had a significantly higher risk of postoperative facial nerve paresis, liquorrhea and lower probability of hearing preservation. Patients with smaller tumors and those, who suffered from headaches before surgery had more frequent and severe headaches after surgery. Postoperative headaches were associated with higher incidence of anxiety and tinnitus. More frequent anxiety was also identified in patients with preoperative serviceable hearing who became deaf after surgery. Nevertheless, tinnitus and hearing impairment appeared to have less impact on overall quality of life compared to headaches and facial nerve function. CONCLUSION: According to our results, tumor size, postoperative function of the facial nerve and occurrence of postoperative headaches had the greatest influence on the overall postoperative quality of life in patients after vestibular schwannoma surgery.

High incidence of occult familial SDHD cases amongst Czech patients with head and neck paragangliomas.

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.

Stimuli-Responsive Polymer Nanoprobes Intended for Fluorescence-Guided Surgery of Malignant Head-and-Neck Tumors and Metastases.

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%.

C-reactive protein as an early marker of postoperative leakage in patients after endoscopic laser assisted Zenker's diverticulotomy.

BACKGROUND AND AIM: Minimally invasive endoscopic techniques are the treatment of choice for Zenker's diverticulum (ZD). Our objective was to evaluate the results and efficacy of endoscopic and open approaches, to determine whether postoperative C-reactive protein (CRP) serum levels can be used as a marker to exclude the presence of esophageal leakage, and to identify risk factors for development of postoperative leakage and complications. MATERIALS AND METHODS: Patients who underwent transcervical myotomy and diverticulotomy (TMD) or endoscopic cricopharyngeal myotomy (ECM) with CO2 laser for ZD in years 2008-2021 at our department were included in this retrospective study. RESULTS: Of the 101 patients enrolled, 83 patients underwent ECM and 18 TMD. The procedure time of the endoscopic technique was significantly shorter compared to that of transcervical method (p < 0.001). The median time to oral intake was 6 days for ECM and 10.5 days in the TMD group (p < 0.001). There was a 13% (n = 11) and 16.7% (n = 3) symptomatic recurrence rate and 3.6% (n = 3) and 16.7% (n = 3) major complications rate for ECM and TMD groups, respectively. The incidence of contrast leak (CL) evaluated by postoperative swallow study was 8.9% (9 from 83 patients in the ECM group only). In patients with CL, a significant increase in CRP levels on postoperative day (POD) 2 and 3 was detected when compared to patients without CL. CONCLUSIONS: Endoscopic diverticulotomy with CO2 laser represents a safe and efficient treatment of ZD. Elevation of postoperative CRP serum levels over 123.8 mg/L on POD2 and 98.8 mg/L on POD3 may indicate presence of an esophageal leakage.

Target-like chondrocytes with thick perichondrocytic rings in cartilage-forming tumours. Preliminary report.

BACKGROUND: Here we present our experience with the occurrence of neoplastic chondrocytes with target-like appearance surrounded with unusual hypertrophic thick eosinophilic perichondrocytic rings (baskets), sometimes containing two or several layers. METHODS AND RESULTS: Pericellular rings (baskets) were positive in APAS and Masson's staining method and showed immunoreactivity with antibody against type IV collagen. Such single cells or small groups of such cells were observed rarely in 3 osteochondromas, 2 skeletal chondromas, 2 extraskeletal chondromas and 2 skeletal and 1 laryngeal chondrosarcomas. Moreover, 1 unusual soft tissue chondrosarcoma was composed entirely of target-like chondrocytes with hypertrophic extremely thick perichondrocytic rings. Such cartilage-forming tumour with target-like cells, which, to the best of our knowledge, is the first such chondrosarcoma reported in the literature. Ultrastructural evidence is presented that perichondrocytic rings have complicated structure.They contained microfibrillar component with abundant admixture of irregular aggregates of dense amorphous non-fibrillar material localised in lacunar spaces. In outer part of the rings predominated microfibrillar structures corresponding to type VI collagen that produced a rather dense capsule-like demarcation line against surrounding intercellular spaces. CONCLUSIONS: The described unusual changes are probably the result of hyperproduction and remodelation of perichondrocytic matrix by abnormal neoplastic chondrocytes in response to unknown factors. Local vascular and molecular signals, may be supposed as probable causes of this phenomenon.

HPMA-Based Copolymers Carrying STAT3 Inhibitor Cucurbitacin-D as Stimulus-Sensitive Nanomedicines for Oncotherapy.

The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition-fragmentation chain transfer polymerization to reach molecular weight Mn about 2 × 104 g·mol-1 and low dispersity. These linear or self-assembled micellar conjugates, containing immunomodulatory agent cucurbitacin-D (CuD) or the anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond, showed a hydrodynamic size of 10-30 nm in aqueous solutions. The CuD-containing conjugates were stable in conditions mimicking blood. Importantly, a massive release of active CuD in buffer mimicking the acidic tumor environment was observed. In vitro, both the linear (LP-CuD) and the micellar (MP-CuD) conjugates carrying CuD showed cytostatic/cytotoxic activity against several cancer cell lines. In a murine metastatic and difficult-to-treat 4T1 mammary carcinoma, only LP-CuD showed an anticancer effect. Indeed, the co-treatment with Dox-containing micellar polymer conjugate and LP-CuD showed potentiation of the anticancer effect. The results indicate that the binding of CuD, characterized by prominent hydrophobic nature and low bioavailability, to the polymer carrier allows a safe and effective delivery. Therefore, the conjugate could serve as a potential component of immuno-oncotherapy schemes within the next preclinical evaluation.

Micelle-Forming Block Copolymers Tailored for Inhibition of P-gp-Mediated Multidrug Resistance: Structure to Activity Relationship.

Multidrug resistance (MDR) is often caused by the overexpression of efflux pumps, such as ABC transporters, in particular, P-glycoprotein (P-gp). Here, we investigate the di- and tri- block amphiphilic polymer systems based on polypropylene glycol (PPO) and copolymers of (N-(2-hydroxypropyl)methacrylamide) (PHPMA) as potential macromolecular inhibitors of P-gp, and concurrently, carriers of drugs, passively targeting solid tumors by the enhanced permeability and retention (EPR) effect. Interestingly, there were significant differences between the effects of di- and tri- block polymer-based micelles, with the former being significantly more thermodynamically stable and showing much higher P-gp inhibition ability. The presence of Boc-protected hydrazide groups or the Boc-deprotection method did not affect the physico-chemical or biological properties of the block copolymers. Moreover, diblock polymer micelles could be loaded with free PPO containing 5-40 wt % of free PPO, which showed increased P-gp inhibition in comparison to the unloaded micelles. Loaded polymer micelles containing more than 20 wt % free PPO showed a significant increase in toxicity; thus, loaded diblock polymer micelles containing 5-15 wt % free PPO are potential candidates for in vitro and in vivo application as potent MDR inhibitors and drug carriers.