Long-Term Care and Follow-Up in Laryngeal Cancer Patients: A Multicenter Retrospective Analysis.

PURPOSE: We conducted an outcome analysis on surgically treated laryngeal squamous cell carcinoma (LSCC) patients. METHODS: A multicenter retrospective study with 352 patients was analyzed. A new nomogram that incorporates age, T- and N-classification, and treatment was created. RESULTS: 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 (n = 29; 8.2%) followed by other head and neck cancers (n = 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). CONCLUSION: 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.

CLINICAL COURSE OF THE DISEASE AND TREATMENT OUTCOME IN PATIENTS WITH MALIGNANT LARYNGEAL TUMOR: RETROSPECTIVE FIVE-YEAR ANALYSIS.

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.

Posttraumatic Vernet syndrome without fracture: A case report and short literature review.

RATIONALE: 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. PATIENT CONCERNS: A patient presenting with dysphagia, extreme hoarseness, and limited shoulder movement after head injury was admitted to the emergency department. DIAGNOSES: Multidisciplinary evaluation was performed, and nerve traction-induced Vernet syndrome was established as a running diagnosis. INTERVENTIONS: Intensive swallowing and speech exercises, assisted by a specialist, were performed. OUTCOMES: 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. LESSONS: 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.

IMP3 Protein Overexpression Is Linked to Unfavorable Outcome in Laryngeal Squamous Cell Carcinoma.

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.

Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma.

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.

New insights into erythropoietin and erythropoietin receptor in laryngeal cancer tissue.

ABSTRACT: To investigate whether laryngeal cancer cells express erythropoietin (Epo) and erythropoietin receptor (EpoR) and what is their possible relationship with clinical and pathological features of the tumor.We performed immunohistochemical analysis of Epo and EpoR expression on 78 tissue samples of invasive and in situ squamous cell laryngeal carcinoma.The statistical analysis showed a weak positive and statistically significant correlation of EpoHS and EpoR HS expression levels. Epo HS and EpoR HS levels did not correlate with patient sex or age, type of diagnosis, cancer stage, histological tumor grade, presence or absence of disease recurrence, type of oncologic cancer therapy provided, or results of selected laboratory blood work. The results show a statistically significant difference in Epo expression with respect to survival.We confirmed the presence of Epo an EpoR in malignant laryngeal tumors and demonstrated the correlation between Epo expression and survival. Further studies are needed to more precisely define the role of Epo and EpoR in treatment of patients with laryngeal cancer.

The expression of ribonuclear protein IMP3 in laryngeal carcinogenesis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Immunohistochemical analysis of vocal cord polyps applying markers of squamous cell carcinogenesis.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Multivariate analysis of risk factors for postoperative wound infection following oral and oropharyngeal cancer surgery.

PURPOSE: The goal of this study was to identify risk factors for wound infections in patients with oral cancer who underwent surgical procedures. MATERIALS AND METHODS: This study included 195 patients who underwent surgical treatment of oral and oropharyngeal cancer over a 7-year period. Wound infection was defined as the occurrence of purulent content from the wound or as an appearance of exudate with signs of local infection and positive cultures taken from the wound. For every patient who was suspected to have a wound infection, a swab from the wound was taken, and microbiological analysis was performed. The patients were divided into 2 groups: patients with postoperative wound infections, and patients with postoperative wound infection. RESULTS: Wound infection was present in 155 patients (59%). Univariate analysis indicated that the following factors were significantly related to the occurrence of wound infection: gender, smoking, tumor localization, size and stage of the tumor, type of surgery, neck dissection, type of reconstruction, nasogastric sonde, gastrostomy and tracheotomy. On multivariate analysis, statistically significant predictors of wound infection were gender, tumor localization and type of reconstruction. CONCLUSIONS: The occurrence of wound infection is high despite antibiotic prophylaxis. To minimize the risk of wound infection and for prompt recognition of risk factors, surgeons managing oral tumor patients should have a better understanding of the risk factors such as gender, tumor localization and type of reconstruction.

Myxoma of the zygomatic bone--a case report.

Myxoma is a benign tumor composed of primitive connective tissue cells and mesenchymal mucousal stroma. Also referred to as, a gelationus or colloidal tumor. Although rare, it can be found in the atrium of the heart, and it is the most common heart tumor. It has also been described in other body sites, one of which is the bone. We report a case of a 57-year-old female patient, with recurrent headaches located in the area of the right half of the face. Radiological analysis (Multislice Computed Tomography of the paranasal sinuses and viscerocranium) was performed, and a formation of irregular contours, destroying the right zygomatic bone, was described, measuring 25 x 17 x 20 mm in its widest diameters. Its me- dial border was adjacent to the lateral wall of the right maxillary sinus and the cortical bone in this segment was thinned, but preserved. A probatory excision was performed in general anesthesia, and the histopathological finding showed, star-like tumor cells embedded in mucoid stroma and infiltrating the bone. After pathohistological confirmation of myxoma, the tumor was excised in total, using infraorbital surgical approach to the zygomatic bone. During the follow-up, the patient was symptom free, without headaches, and there were no signs of local tumor recurrence. Despite of the fact that myxoma behaves as a benign disease in its nature, it can cause destruction of the tissue in the vicinity of the tumor itself and thus major health issues for the patient. A timely proper diagnosis and the right choice of a surgical treatment can help avoid more extensive surgery procedures, as shown in our case report.