The membrane EGFR (mEGFR) protein overexpression in the head and neck squamous cell carcinoma (SCC) is considered to cause increased EGFR activity which adds to tumorigenicity and therapy resistance. ...The mEGFR upon stimulation can translocate to the nucleus nuclear EGFR (nEGFR) where it has been associated with poor prognosis and worse survival in many cancers. The relevance of differentially located EGFR proteins in laryngeal lesions has not been studied enough and remains unclear. Aim of our study was to examine nEGFR and mEGFR protein expression as well as EGFR gene status and cell cycle proliferation markers in the laryngeal polyps, dysplasia, and SCC using immunohistochemistry and in situ hybridization. There was significantly higher frequency of strong nEGFR between SCC, dysplasia, and polyps (P<0.0001), and strong mEGFR in the SCC and laryngeal dysplasia comparing to polyps (P<0.0001). Gene amplification was confirmed only in relatively small number of SCC but not in non-neoplastic lesions. In dysplasia the statistically significant positive correlations between nEGFR, and Ki-67 (P=0.029), p53 (P=0.001), and cyclin D1 (P=0.031) were found. nEGFR and mEGFR expression showed statistically significant inverse correlation in the SCC (P=0.004) as well as nEGFR and cyclin D1 (P=0.032). Univariate statistical analysis showed statistically significant correlation between strong nEGFR protein expression and worse overall survival in laryngeal SCC, alone or in coexpression with strong cyclin D1 and high Ki-67 (P=0.025, P=0.046, P=0.043, respectively). Our data show that nEGFR cellular localization might influence biology of the laryngeal carcinogenesis and is indicator of poor survival.
The aim of this case is to emphasize the need to include nerve traction in the differential diagnosis of nerve deficits associated with Vernet syndrome. This mechanism of injury has been described ...only once, but must not be overlooked and should be considered and included as a possible cause in diagnostic algorithms.
A patient presenting with dysphagia, extreme hoarseness, and limited shoulder movement after head injury was admitted to the emergency department.
Multidisciplinary evaluation was performed, and nerve traction-induced Vernet syndrome was established as a running diagnosis.
Intensive swallowing and speech exercises, assisted by a specialist, were performed.
Swallowing and speech exercises significantly and objectively improved the patient's swallowing and voice, with mild hoarseness of voice remaining as the main symptom. Spectral acoustic analysis went from a voice pitch of 163.77 Hz to normal (187.77 Hz), jitter improved from 17.87% to 0.86% and shimmer values decreased from 39.86% to 19.60%. Breathiness during phonation measuring 2.91% was reduced to 1.08% and appropriate average intensity of voice (63.95 dB) was achieved. Initial dysphagia and fluid retention in the right piriform sinus, along with tracheal aspiration, were not observed in control fiberoptic endoscopic evaluation of swallowing.
According to our knowledge and literature data, this is the second reported case of posttraumatic Vernet syndrome without radiologically confirmed jugular foramen fracture, induced by nerve traction. Such patients need a prompt multidisciplinary approach in diagnosis and timely posttraumatic rehabilitation therapy for favorable clinical evolution and retrieval of nerve function.
The aim was to investigate clinical course of disease in patients with malignant laryngeal tumors with emphasis on various forms of disease recurrence (local recurrence, metastasis to regional lymph ...nodes, occurrence of second primary tumor). A retrospective research including 78 patients with histopathologically confirmed diagnosis of squamous cell laryngeal carcinoma was conducted. Information on cancer stage, histologic grade, type of treatment and disease recurrence was obtained from medical history. Tissue samples of the patients were submitted to immunohistochemical analysis and assessment of Ki-67 proliferation index expression. The occurrence of second primary tumor was found to be related to the significantly higher Ki-67 proliferation index. The number of patients having not undergone oncologic therapy and remained free from disease recurrence was significantly higher than expected. Treatment outcome depends on patient age, histologic grade, radiotherapy applied, and clinical course of disease. It is necessary to define the predictive factors of various forms of disease recurrence more precisely in order to identify better treatment options for patients with malignant tumors of the larynx.
The aim of the study was to investigate the expression of ribonuclear protein IMP3 in laryngeal carcinogenesis, together with other biomarkers of carcinogenesis (Ki-67, p53 and cyclin D1), and to ...evaluate their predictive values.
The study included 153 patients divided into three groups: 68 operated for primary invasive laryngeal squamous cell carcinoma (LSCC); 41 with precancerous lesions of atypical and abnormal hyperplasia; 44 with hyperplastic laryngeal nodule without atypia. Tissue microarray technique was used for immunohistochemical analysis.
All markers showed statistically significant differences between the three groups. The percentage of IMP3 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of Ki-67 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of p53 positive cells in LSCC group is statistically significantly higher than the control group and higher, but not statistically significant, than the precancerosis group. The percentage of cyclin D1 positive cells is statistically significantly higher in LSCC group than in precancerosis group and higher, but not statistically significant, than in the control group. All analyzed markers have good predictive values (AUC > 0.6), but the percentage of IMP3 positive cells is the only statistically significant marker in predicting whether the patient has LSCC or not.
Expression of Ki-67 and pronouncedly IMP3 generally follow the same pattern where control and precancerosis are similar and LSCC significantly differs, as opposed to p53 and cyclin D1. IMP3 expression increase possibly has an important diagnostic, therapeutic (in terms of the need for additional therapy after surgery) and prognostic value. Further studies on the exact molecular mechanisms behind it are, of course, needed.
The aim of the study was to perform a pathohistological and immunohistochemical analysis of squamous cell (SC) carcinogenesis markers on epithelial linings of vocal cord polyps.
The vocal box, being ...a heavily burdened organ with intensive cell renewal and regenerative processes, is therefore a favourable environment for constant epithelial growth and hyperplasia. In our ongoing projects on laryngeal carcinogenesis and research on laryngeal tissue, we encountered atypia on diagnosed nodules and polyps that are usually considered as benign formations, resulting from the above-mentioned cell renewal and regeneration, which lead to further investigation.
The purpose was to see if changes in molecular markers of SC carcinogenesis follow, or, may appear in immunohistochemical (IHC) analysis, before histological atypia in standard haematoxylin-eosin (HE) staining, and contribute in early diagnosis of potentially suspect polyps.
After classical pathohistological (PH) analysis on HE slides, IHC analysis of EGFR, cyclin D1, p53, Ki-67, and IMP3 was performed on tissue microarrays of laryngeal tissue (50 samples), ranging from normal to hyperplastic lesions with no atypia (34 samples), low-grade atypia (11 samples), and high-grade atypia (5 samples).
This study established an increase and correlation of EGFR, cyclin D1, p53, Ki-67 and IMP3 IHC expressions with pathohistological findings of dysplasia in glottic polypoid lesions. Low and high-grade dysplasia had statistically higher percentages of EGFR-positive cells than normal epithelium and simple hyperplasia (SH) (low vs. normal/SH P = 0.007; high vs. normal/SH P = 0.001). High-grade dysplasia had statistically more positive cells than low-grade dysplasia (P = 0.004), and low-grade dysplasia had statistically more positive cells than specimens without atypia (P = 0.007). The percentage of positive cells was statistically higher for cyclin D1, p53 and Ki-67 in high-grade dysplasia versus low-grade dysplasia (cyclin D1 P = 0.011, p53 P = 0.002; Ki-67 P = 0.026; respectively) and versus normal epithelium and SH (cyclin D1 P = 0.003; p53 P = 0.001; Ki-67 P = 0.002; respectively). An increase of IMP3-positive cells with an increase of atypical changes in the laryngeal epithelium, from superficial towards basal layers was noticed, contrary to the usually seen positivity pattern of SC carcinogenesis markers from basal to superficial layers. A statistically significant difference of IMP3 IHC staining between the pathohistological groups (P = 0.003) was recorded.
Only polyps that present with simple hyperplasia as the greatest mucosal change can be considered as benign formations.
Pathohistologically detected atypia in polypoid changes of vocal cords, confirmed by molecular atypia with an increase of SC carcinogenesis markers, suggest their inclusion in studies of laryngeal carcinogenesis.
Our results suggest that in problematic cases IHC analysis could be of interest in detection of biological aggressiveness in polypoid laryngeal tissue and beneficiary for polyp patients’ follow-up.
Further research of laryngeal carcinogenesis markers and their meaning in fibrovascular polyps is of interest.
Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to ...examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p < 0.001; p < 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.
Cilj : prikaz slučaja bolesnice s dijagnozom invertnog papiloma septuma i retrospektivna analiza dosadašnjih iskustava u liječenju bolesnika sa sinonazalnim invertnim papilomom na Klinici za ...otorinolaringologiju i kirurgiju glave i vrata Kliničkog bolničkog centra Rijeka. Prikaz slučaja: 30-godišnja bolesnica s otežanim disanjem kroz nos i učestalim epistaksama javila se na otorinolaringološki pregled 2022. godine. Endoskopijom nosa utvrđena je perforacija u prednjim regijama septuma. Dijagnostička obrada uključivala je biopsiju sluznice, slikovnu obradu i krvne pretrage za probir na c-ANCA i p-ANCA autoantitijela, kao i test za angiotenzin-konvertirajući enzim (ACE). Nalaz patohistološke analize pokazao je kako se radi o invertnom papilomu te je provedeno kirurško liječenje. Potom je retrospektivnom analizom utvrđeno kako su u razdoblju od travnja 2014. do ožujka 2022. godine u Klinici za otorinolaringologiju i kirurgiju glave i vrata Kliničkog bolničkog centra Rijeka liječena 22 bolesnika s dijagnozom sinonazalnog invertnog papiloma. Iskustva s njihovim liječenjem također su prikazana u ovom radu. Zaključak : Bolesnici sa sinonazalnim invertnim papilomom uspješno se liječe u našoj ustanovi endoskopskom kirurgijom sinusa. Diferencijalno-dijagnostički o ovom je tumoru potrebno razmišljati i u mladih bolesnika i bolesnica s atipičnom prezentacijom bolesti. Potrebna su daljnja istraživanja u svrhu razjašnjenja etiologije bolesti i mogućnosti predikcije recidivizma i/ili maligne alteracije ovih tumora.
Aim : We present a case of a female patient diagnosed with inverted papilloma of the nasal septum and retrospective analysis of previous experiences in the treatment of patients with sinonasal inverted papilloma. The patients were treated at the Clinic for Otolaryngology and Head and Neck Surgery in the Clinical Hospital Center Rijeka. Case report: A 30-year-old patient with difficulty in breathing through the nose and frequent epistaxis came for an otolaryngological examination in 2022. Nasal endoscopy revealed a perforation in the anterior regions of the septum. Diagnostic process included mucosal biopsy, imaging, and blood tests to screen for c-ANCA and p-ANCA autoantibodies, as well as an angiotensin-converting enzyme (ACE) test. Pathohistological analysis established the diagnosis of inverted papilloma and surgical treatment was performed. After this case we did a retrospective analysis and established that in the period from April 2014 to March 2022, 22 patients with sinonasal inverted papilloma were treated in the Clinic for Otorhinolaryngology and Head and Neck Surgery, Rijeka Clinical Hospital Center. Experiences with their treatment are also presented in this paper. Conclusion : Patients with sinonasal inverted papilloma are successfully treated in our institution. Differential diagnosis of this tumor should be considered in young patients with atypical disease presentation. Further research is needed in order to clarify etiology and predict the possibility of recurrence and / or malignant alteration of these tumors.
We conducted an outcome analysis on surgically treated laryngeal squamous cell carcinoma (LSCC) patients.
A multicenter retrospective study with 352 patients was analyzed. A new nomogram that ...incorporates age, T- and N-classification, and treatment was created.
Recurrence was observed in 65 (18.5%) patients after a mean time of 16.5 months. After 60 months, 91 (25.9%) of patients developed secondary primary tumors (SPT), most commonly in the lungs (
= 29; 8.2%) followed by other head and neck cancers (
= 21; 6.0%). Notably, the mean time to occurrence of secondary head and neck cancers was twice that of lung cancer (101.1 vs. 47.5 months).
Recurrent disease is less common in LSCC patients and appears much earlier than SPT. Because one in every four laryngeal cancer patients develops SPTs within 5-10 years, long-term care and follow-up, including imaging studies, are highly recommended. The nomogram was useful for estimating survival.
Vrtoglavica i omaglica jedni su od najčešćih razloga zbog kojih bolesnici traže liječničku pomoć te su uzrok otprilike 3,5 % svih posjeta hitnoj medicinskoj službi. Veoma je bitno prepoznati životno ...ugrožavajuće vrtoglavice, koje zahtijevaju neposredno zbrinjavanje, te ih razlikovati od „benignih“, samolimitirajućih stanja. Upravo stoga bolesnici s akutnom vrtoglavicom često predstavljaju dijagnostički i terapijski izazov nadležnom liječniku. Aktualan pristup bolesniku s akutnom vrtoglavicom ne uzima u obzir samo kvalitetu simptoma, već stavlja naglasak i na vrijeme nastanka tegoba, trajanje, provokacijske čimbenike, prateće simptome i informacije o potencijalnim prijašnjim epizodama. S obzirom na vrijeme trajanja simptoma i provokacijske čimbenike, akutne vrtoglavice možemo svrstati u tri skupine: akutni (jednokratni) vestibularni sindrom, spontani povratni vestibularni sindrom i izazvani povratni vestibularni sindrom. Akutni vestibularni sindrom (AVS) označava iznenadnu pojavu vrtoglavice koja traje dulje od 24 sata, povezan je s mučninom, povraćanjem, nestabilnošću i nistagmusom, a simptomi su dodatno pogoršani pokretima glave. Razni središnji i periferni uzroci mogu potaknuti nastanak AVS-a, od kojih su najčešći vestibularni neuronitis (VN) i moždani udar stražnje cirkulacije. Kao moćan alat za prepoznavanje perifernog vestibularnog sindroma i moždanog udara u literaturi se zadnjih godina zagovara HINTS (engl. Head Impulse, Nystagmus, Test of Skew) plus protokol. Najčešći uzroci perifernog vestibularnog sindroma su benigni paroksizmalni pozicijski vertigo (BPPV), vestibularni neuronitis i Ménièreova bolest. U ovom članku donosimo pregled novijih pristupa koji pomažu u lakšem i bržem razlikovanju „benignih“ od ugrožavajućih oblika vrtoglavica, suvremenog liječenja, kao i pregled najčešćih perifernih vrtoglavica.
Vertigo and dizziness are among the most common reasons for patients to seek medical help and approximately 3.5 % of all emergency department visits are related to them. The acutely dizzy patient can present a diagnostic and management dilemma for emergency departments and physicians in charge of those patients. Hence, it is of great importance to distinguish the life-threatening conditions, which require acute treatment, from “benign”, self-limiting conditions. While the traditional approach to dizziness relies on “symptom quality” or “type”, the new approach is based on symptom timing, triggers, duration, associated symptoms and patient history. Based on timing and triggers, this new approach divides patients into three key categories: acute vestibular syndrome, spontaneous episodic vestibular syndrome and triggered episodic vestibular syndrome. The acute vestibular syndrome (AVS) is defined as the acute onset of persistent dizziness associated with nausea or vomiting, gait instability, nystagmus, and head-motion intolerance lasting longer than 24 hours. AVS is provoked by a variety of central and peripheral causes, the most common of which are vestibular neuritis and acute stroke (posterior circulation). The HINTS (Head Impulse, Nystagmus, Test of Skew) plus protocol is a powerful tool for distinguishing a possible posterior stroke from peripheral vestibular dysfunction and it has been highly recommended recently. The most common causes of peripheral vertigo are benign paroxysmal positioning vertigo (BPPV), vestibular neuritis and Ménière’s disease. In this article we bring a review of new approaches to vertigo which contribute to faster and easier differentiation of benign and life-threatening conditions. A review of the most common types of peripheral vertigo is also included.
Poremećaji gutanja učestala su tegoba kod neuroloških bolesnika. Radi se o tegobama koje znatno narušavaju kvalitetu života, mogu uzrokovati poremećaje hranjenja, malnutriciju, dehidraciju, ali i ...dovesti do aspiracije i aspiracijske pneumonije. Dostupne dijagnostičke metode obuhvaćaju upitnike za probir i samoprocjenu simptoma, protokole logopedske dijagnostike te fiberendoskopiju i videofluoroskopiju, a važna je i procjena nutritivnog statusa bolesnika. Nakon postavljene dijagnoze disfagije poseže se za brojnim rehabilitacijskim postupcima koji omogućavaju ublažavanje simptoma i smanjenje rizika od aspiracije. Katkad se tegobe pokušava umanjiti i kirurškim metodama. U liječenju disfagije u oboljelih od Parkinsonove bolesti istražuje se i korist od duboke moždane stimulacije.
Swallowing disorders are common among neurological patients. They can significantly impair the quality of life, cause eating disorders, malnutrition, dehydration, and increase the risk of aspiration and aspiration pneumonia. Available diagnostic methods include questionnaires for screening of dysphagia symptoms, speech therapy diagnostic protocols, fiberoendoscopy and videofluoroscopy. It is also important to assess the patient’s nutritional status. Plenty of rehabilitation procedures are available for the relief of symptoms and reduction of the risk of aspiration. Surgical methods are sometimes used in the process of treatment. The benefits of deep brain stimulation are being investigated in the treatment of dysphagia in Parkinson’s disease patients.
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