Elective open "Shield Tracheostomy" in patients with COVID-19.

PURPOSE: To prevent the consequences of long-term endotracheal intubation, patients undergo tracheostomies. However, as COVID-19 is highly contagious, its existence has made the tracheostomy a high-risk procedure. Tracheostomy procedures must, therefore, be adjusted for safety reasons. The aim is to present the adjustments that should be made to the surgical technique. METHODS: Both the medical charts and surgical reports of patients with COVID-19 who were subjected to elective open tracheostomies were reviewed. RESULTS: The retrospective study included 25 patients. Our adjustments include the timing of tracheostomies, ideally putting them at 21 days after the onset of COVID-19, the advancement of an endotracheal tube to 26-28 cm from the upper-alveolar ridge, surgery being carried out in the intensive care unit with appropriately modified positions of the patient and providers, tracheo-cutaneous sutures, and intentionally making the small tracheal flap and the tracheal window the same shape as a medieval shield. CONCLUSIONS: A tracheostomy performed in this way is now referred to as the Shield Tracheostomy. Further improvements to the surgical technique are expected in the future.

Emergent tracheostomy during the pandemic of COVID-19: Slovenian National Recommendations.

PURPOSE: Emergent tracheostomy under local anaesthesia is a reliable method of airway management when orotracheal intubation is not possible. COVID-19 is spread through aerosol making the emergent tracheostomy a high-risk procedure for surgeons. The surgical establishment of the air conduit in emergency scenarios must be adjusted for safety reasons. METHODS: To establish the Slovenian National Guidelines for airway management in cannot intubate-cannot ventilate situations in COVID-19 positive patients. RESULTS: Good communication and coordination between surgeon and anaesthesiologist is absolutely necessary. Deep general anaesthesia, full muscle relaxation and adequate preoxygenation without intubation are initial steps. The surgical cricothyrotomy is performed quickly, the thin orotracheal tube is inserted, the cuff is inflated and ventilation begins. Following patient stabilisation, the conversion to the tracheostomy is undertaken with the following features: skin infiltration with vasoconstrictor, a vertical incision, avoidance of electrical devices in favour of classical manners of haemostasis, the advancement of the tube towards the carina, performing the tracheal window in complete apnoea following adequate oxygenation, the insertion of non-fenestrated canulla attached to a heat and moisture exchanger, the fixation of canulla with stitches and tapes, and the cricothyrotomy entrance closure. Appropriate safety equipment is equally important. CONCLUSION: The goal of the guidelines is to make the procedure safer for medical teams, without harming the patients. Further improvements of the guidelines will surely appear as COVID-19 is a new entity and there is not yet much experience in handling it.

Squamous cell carcinoma of unknown primary tumor metastatic to neck nodes: role of elective irradiation.

In patients with squamous cell carcinoma (SCC) metastases to neck lymph nodes and unknown primary tumor, the role of elective irradiation of uninvolved neck and potential mucosal primary sites is yet to be determined. The aim of this study was to review the experience treating SCC of unknown primary metastatic to neck nodes with surgery and postoperative radiotherapy (PORT) in Slovenia between 1995 and 2010 and to determine the importance of the extent of irradiated volume. For this purpose, the nationwide Cancer Registry of Slovenia database was used for identifying patients. 126 patients were identified. Involved-field PORT and extended-field PORT was used in 50 and 76 patients, respectively. At 5 years, locoregional control was 86 %, disease-specific survival 77 %, and overall survival 57 %. In multivariate analysis, the extent of irradiated volume has not been predictive for any outcome under study. Grade ≥3 acute and late radiotherapy-induced toxicities were more frequent in the extended-field PORT group. In conclusion, although not superior, involved-field PORT seems to be a preferred treatment option in SCC of unknown primary metastatic to neck nodes due to significantly reduced toxicity and better prospects for successful salvage.

Pharyngocutaneous fistula: the incidence and the risk factors.

A pharyngocutaneous fistula is the most common complication following laryngectomy. A wide range of potential risk factors has been suggested. The purpose of this study was to determine the incidence and risk factors for the fistula at the Department of Otorhinolaryngology and Head and Neck Surgery in Ljubljana, Slovenia between 2007 and 2012. Charts from patients treated for head and neck cancer by laryngectomy were retrospectively reviewed. Comprehensive clinicopathologic data were collected including potential risk factors related to the patient, disease, surgery and postoperative period. The patients were categorised into the group with the fistula (a study group) and without it (a control group). The incidence of the fistula was calculated and the groups were statistically compared according to potential risk factors using the Chi square test, Fisher exact test, T test, Mann-Whitney U test and binary logistic regression analysis. Hundred fifty-eight patients were included. The incidence of the fistula was 30.4 %. In the primary laryngectomy group the incidence was 22.6 %, whereas in the salvage laryngectomy group 44.6 % (p = 0.006). The independent predictors for the fistula were history of head and neck cancer (p = 0.001), invasion of piriform sinus (p = 0.020) and surgical wound infection (p < 0.001). The timing of surgical wound infection could be of some importance. In the PCF group, it started on the 5th postoperative day, whereas in the control group on the 7th postoperative day (p = 0.063). Decreasing the rate of surgical wound infection could diminish the fistula rate.

Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery.

PURPOSE: To analyze the oncologic, functional, and esthetic results of using the pectoralis major myocutaneous flap (PMMF) from November 2001 to April 2012 at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Center Ljubljana (Ljubljana, Slovenia). PATIENTS AND METHODS: Patients with squamous cell carcinoma of the head and neck (SCCHN) who underwent tissue defect reconstruction with a PMMF were identified from a prospective database. Medical and surgical records were reviewed for information on clinical characteristics, treatment, and outcome and specifically for indications for the PMMF, wound healing, flap vitality, functional results, and esthetics. RESULTS: Forty PMMFs were used in 39 patients with SCCHN. With respect to previous therapy and prognosis, patients were sorted into a primary surgery group (19 patients) and a salvage surgery group (20 patients with recurrent disease). Statistically better locoregional control and disease-free survival were observed in the first group. Wound healing was completed in 32 patients (median time from surgery, 22 days). Three cases exhibited partial PMMF necrosis. Functional results, occlusion of pharyngocutaneous fistula, speech intelligibility, upper limb dysfunction, and esthetic outcome did not differ between the 2 groups. CONCLUSION: The PMMF is a reasonable choice for primary head and neck cancer surgery and in salvage procedures. Its use is characterized by vitality, a reasonably short recovery time, and a favorable esthetic outcome at the donor site in most patients.

Expression of stefin A is of prognostic significance in squamous cell carcinoma of the head and neck.

Lysosomal proteases cathepsins B and L (CB, CL) and their endogenous inhibitors stefins A and B (SA, SB) are associated with tumor cell invasion and metastasis. The purpose of this study was to determine the immunohistochemical (IHC) localization of these parameters in tissue sections of 65 patients with operable head and neck squamous cell carcinoma (HNSCC) and to evaluate the prognostic significance of the observed IHC reactions. In SCC cells, a dot-like staining pattern for CB and CL was especially polarized in the perinuclear area and for stefins the characteristic IHC pattern was a diffuse cytoplasmic reaction. Higher SA immunoreactivity scores were found prognostically advantageous in univariate survival analysis [locoregional control (LRC), P = 0.003; disease-free survival (DFS), P = 0.023; disease-specific survival (DSS), P = 0.030] and appeared significant for predicting LRC (P = 0.019) in a multivariate setting. Among node-positive extracapsular extension-negative patients, SA positivity correlated with a favorable outcome (LRC, P = 0.094; DFS, P = 0.013; DSS, P = 0.012). In conclusion, SA immunoreactivity in tumor cells was related to a favorable prognosis. In the neck node-positive extracapsular extension-negative subgroup, SA immunoreactivity scores can be used to identify patients at increased risk for disease relapse.

Sialendoscopy-Based Analysis of Submandibular Duct Papillae with a Proposal for Classification.

Identifying a submandibular (Wharton's) duct punctum often hinders sialendoscopy; however, there is a paucity of evidence on whether the appearance of Wharton's duct papilla impacts the sialendoscopic procedure. A classification of Wharton's duct papillae based on the macroscopic appearance, size of dilatation probes, and sialendoscopic approach was proposed herein. The classification describing four main types of papillae, A, B, C, and D, was prospectively evaluated on 351 Wharton's duct papillae in 315 patients. For each papillae type, the demographic/clinical data, intraoperative complications, and time required for sialendoscope introduction were analyzed. Estuary-like papilla (type A) was commonly seen after spontaneous stone extrusion, had no intraoperative complications noted, and had the shortest time required for the sialendoscope introduction. Normal papilla (type B) was the most frequently observed papilla (48.1%), reflecting diverse underlying pathology, while difficult papilla (type C) was often associated with unfavorable anatomical variations of the mandible or floor of the mouth. Substantially closed papilla (type D) had the highest rate of intraoperative complications, namely, perforation with a false passage, and required the longest time for the sialendoscope introduction. In seven patients (2.0%), the entrance into the duct was feasible only through the fistula, while the sialendoscope introduction failed in eight patients (2.3%). In conclusion, the appearance of Wharton's duct papillae may be influenced by the underlying pathology. Based on the proposed classification, papilla typology affects the duration of sialendoscope introduction and may influence the frequency of intraoperative complications.

The Incidence and the Risk Factors for Pharyngocutaneous Fistula following Primary and Salvage Total Laryngectomy.

The pharyngocutaneous fistula (PCF) is the most common complication following a total laryngectomy (TL) with a wide range of incidence and various potential risk factors. The aim was to analyse the incidence and potential risk factors for PCF formation in a large study set collected over a longer period of time. In the retrospective study at the Department of Otorhinolaryngology and Cervicofacial Surgery of Ljubljana, 422 patients who were treated for head and neck cancer by TL between 2007 and 2020 were included. The comprehensive clinicopathologic data were collected including potential risk factors related to the patient, disease, surgical treatment and post-operative period for the development of fistulae. The patients were categorized into a group with the fistula (a study group) and one without it (a control group). The PCF then developed in 23.9% of patients. The incidence following a primary TL was 20.8% and 32.7% following salvage TL (p = 0.012). The results demonstrated that surgical wound infection, piriform sinus invasion, salvage TL, and total radiation dose were determined as independent risk factors for PCF formation. A diminishing surgical wound infection rate would contribute to a further reduction of the PCF rate.

Sialendoscopy in Management of Juvenile Recurrent Parotitis-A Single Centre Experience.

Juvenile recurrent parotitis is a rare inflammatory disease of the parotid gland that shares diverse therapeutic management between institutions. Sialendoscopy has been demonstrated as an efficient diagnostics and therapeutic method with minimal complications; however, due to the rarity of the disease and limited data, there is a lack of universal guidelines on its optimal management. Herein, we retrospectively analysed patients with juvenile recurrent parotitis who had the sialendoscopy performed at our tertiary centre. Descriptive data were retrieved along with the number of swelling episodes one year before and after the sialendoscopy intervention. In the last decade, twenty-nine sialendoscopic procedures were performed at our clinics on twenty-one patients diagnosed with juvenile recurrent parotitis. Most of them underwent the procedure under general anaesthesia (86%). In the year before and after the sialendoscopic procedure, the patients had 3.9 ± 2.7 and 0.2 ± 0.4 episodes of swelling per year, respectively. The difference proved to be statistically significant (p < 0.0001). The complete resolution was noted in sixteen patients (76%); however, the procedure was not repeated on the same side of any patient. Solely one patient had a relapse of the disease reported more than twelve months after the sialendoscopy, nonetheless, one of his exacerbation episodes was already reported in the first year after the sialendoscopy. The mean follow-up period of patients was 48.6 months (range, 13−116 months). All things considered, this study emphasises sialendoscopy as an effective minimally invasive diagnostic and therapeutic tool for the management of juvenile recurrent parotitis.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

Sialendoscopy and CT navigation assistance in the surgery of sialolithiasis.

BACKGROUND: A sialendoscopy-assisted combined approach is well established in the surgery of sialolithiasis. In cases of proximal salivary stones, transcutaneous sialendoscopy-assisted extractions with parotid and submandibular gland preservation is the primary intention of treatment. We recently added computer tomography (CT) navigation to improve the results of this challenging surgery equally in both localizations. PATIENTS AND METHODS: Al l the patients who submitted to sialendoscopy and sialendoscopy-assisted procedures at the tertiary institution between January 2012 and October 2020 were included in the present study. From November 2019, CT navigation was added in cases with sialolithiasis and a presumably poor sialendoscopic visibility. We evaluated the parameters of the disease, diagnostic procedures, sialendoscopic findings and outcomes, with or without optical surgical navigation. RESULTS: We performed 178 successful salivary stone removals in 372 patients, of which 118 were combined sialendos-copy-assisted approaches, including 16 transcutaneous proximal, 10 submandibular and 6 parotid stone operations. Surgical navigation was used in six patients, four times for submandibular and twice for parotid sialolithiasis. These were all non-palpable, sialendoscopically invisible or partially visible stones, and we managed to preserve five of the six salivary glands. CONCLUSIONS: The addition of CT navigation to sialendoscopy-assisted procedures for non-palpable, sialendoscopically invisible and fixed stones is a significant advantage in managing sialolithiasis. By consistently performing sialendoscopy and related preservation procedures, we significantly reduced the need for sialoadenectomies in patients with obstructive salivary gland disease.

The importance of flaps in reconstruction of locoregionally advanced lateral skull-base cancer defects: a tertiary otorhinolaryngology referral centre experience.

BACKGROUND: The aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer. PATIENTS AND METHODS: The retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. RESULTS: Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. CONCLUSIONS: Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.

Usefulness of high-risk human papillomavirus mRNA silver in situ hybridization diagnostic assay in oropharyngeal squamous cell carcinomas.

AIMS: The transcriptional activity of high-risk human papillomaviruses (HR-HPV) within oropharyngeal squamous cell carcinomas (OPSCC) has been linked to improved survival of patients. HR-HPV mRNA silver in situ hybridization (SISH) was evaluated on a cohort of OPSCC and compared with viral HPV DNA tests and p16 expression. Clinical outcomes of HPV-driven OPSCC and non-HPV related OPSCC were also studied. METHODS: We evaluated 67 OPSCC and 3 papillomas, obtained from 62 patients, for detection of HR-HPV DNA by PCR tests. The positive samples were additionally studied by the SISH method using three probes of HPV16, HPV18, and HP33, and for p16 expression detected by immunohistochemistry. SISH assays were evaluated for the presence/number and intensity of signals in cancer cells. Prognostic significance of HPV status in our cohort was evaluated with univariate and multivariate statistics. RESULTS: According to the HR-HPV PCR tests, 46 (69%) OPSCC cases were HPV positive, while three papillomas were negative. Of total 46 HPV-positive OPSCCs, 43 cases were also SISH-positive, while p16 overexpression was found in 45 of 46 HPV positive OPSCC cases. In OPSCC specimens, the sensitivity and specificity of the combined SISH probes (HPV16 and 33) were both 100.00%, when compared to HPV PCR. HPV positivity of the tumors appeared significant for predicting progression-free survival, cause specific survival and overall survival in a multivariate setting. CONCLUSIONS: The recently developed mRNA SISH methodology can detect HPV-driven OPSCCs without any additional test in 79% of cases. Positive SISH signals enable the visualization of viral transcripts required to recognize clinically relevant HPV infection. However, rare and tiny signals require an experienced pathologist to establish a consensus interpretation of results. The currently applied HR-HPV mRNA SISH analysis may serve as a groundwork for additional studies.

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of NANOG, miR-34a, miR-145, RoR, SNHG1, AB209630, and TP53 was performed using qPCR and immunohistochemistry for NANOG protein detection. NANOG protein showed no staining in normal mucosa, very weak in low-grade dysplasia, and strong staining in high-grade dysplasia and OSCC. NANOG, miR-145, RoR, and SNHG1 showed up-regulation, TP53 and miR-34a showed down-regulation, and AB209630 showed variable expression during cancerogenesis. NANOG mRNA was up-regulated early in cancerogenesis, before strong protein expression can be detected. NANOG was in correlation with miR-145 and RoR. Our results suggest that miRNAs and lncRNAs, particularly miR-145 and RoR, might be important post-transcription regulatory mechanisms of NANOG in OSCC cancerogenesis. Furthermore, NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.

concomitant chemoradiotherapy with mitomycin C and cisplatin in advanced unresectable carcinoma of the head and neck: phase I-II clinical study.

PURPOSE: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m(2) IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m(2)/d IV, applied during the last 10 fractions of irradiation ("chemoboost"). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m(2)/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m(2)/d (Phase I study), which was tested in the subsequent Phase II study. RESULTS: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m(2)/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m(2)/d, the corresponding rates were 40%, 20%, and 22%, respectively. CONCLUSION: Concomitant chemoradiotherapy with mitomycin C and cisplatin "chemoboost" at 14 mg/m(2)/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

Stefin a and stefin B: markers for prognosis in operable squamous cell carcinoma of the head and neck.

PURPOSE: The aim of this study was to test the hypothesis about the protective role of high stefin A and stefin B concentrations in operable carcinoma of the head and neck. METHODS AND MATERIALS: Stefins A and B concentrations were measured in tissue cytosols of nontumorous mucosa and primary tumors from 92 patients. For quantitative analysis of stefins in tumor cytosols, commercially available enzyme-linked immunosorbent assays were used. RESULTS: Stefin A was upregulated in 53 patients (higher concentrations were measured in tumor samples than in nontumorous mucosa) and was downregulated in 39 patients. The corresponding numbers for stefin B were 49 and 43, respectively. A significantly higher proportion of downregulated cases were found among patients with disease re-appearance. In the Cox model, high stefin A concentrations appeared as independent predictors for favorable disease-free survival. Assuming a "broken stick" model, a significant increase in the recurrence rate after the threshold of 1063 ng/mgp (the 64th percentile in the group) was found, the hazard ratio reaching 3% of the reference value with doubling of the level of stefin A. These results were reconfirmed after pooling the data with two historical data sets into a uniform series involving 182 patients. CONCLUSIONS: A group of patients at high risk for disease progression was identified, characterized by the downregulated stefin A protein in the tumor compared with the nontumorous mucosa. Stefin A was recognized as a promising candidate marker for prognosis in patients with operable carcinoma of the head and neck.

The assessment of mucosal surgical margins in head and neck cancer surgery with narrow band imaging.

OBJECTIVES/HYPOTHESIS: The diagnostic gain of narrow band imaging in the definition of surgical margins in the treatment of head and neck cancer was evaluated. STUDY DESIGN: A prospective study, blinded to the pathologist, with historical comparison. METHODS: The study group included 45 patients subjected to the intraoperative definition of margins by narrow band imaging. The control group included 55 patients who had undergone standard definition of margins. All patients underwent resection of the tumor and frozen section analysis of superficial margins. The rate of initial R0 resection and the ratio of histologically negative margins for both groups were statistically compared. RESULTS: The rate of initial R0 resection in the study group and in the control group was 88.9% and 70.9% (P = .047), and the ratio of histologically negative margins was 95.9% and 88.4% (P = .017), respectively. CONCLUSIONS: Narrow band imaging reveals a microscopic extension of the tumor that could be effectively used to better define superficial margins and to achieve a higher rate of initial R0 resections. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1577-1582, 2017.

Mucosal melanoma of the head and neck: a population-based study from Slovenia, 1985-2013.

OBJECTIVES: To assess the incidence and to review experience with the treatment of mucosal melanoma of the head and neck (MMHN) in Slovenia between 1985 and 2013. METHODS: The National Cancer Registry database and clinical records with outcome data of identified patients treated during the period 1985-2013 in Slovenia were reviewed. RESULTS: In a 29-year period, 61 patients with MMHN were identified, representing 0.5 % of all head and neck malignant tumors and 42 % of all mucosal melanomas in Slovenia. 72 % originated in the sinonasal tract and were predominantly (78 %) diagnosed as a local disease. Regional metastases at diagnosis were more frequent in patients with oral/oropharyngeal primary (44 %; sinonasal MMHN 11 %, p = 0.006). Curative intent treatment was given to 48 (79 %) patients. The overall survival (OS) rates at 2 and 5 years for the whole cohort were 43 % and 18 %, respectively, and for the curative intent group 53 % and 24 %, respectively. In the latter group, multivariate analyses showed postoperative radiotherapy (PORT) to be predictive for locoregional control (LRC) (hazard ratios [HR] for surgery with PORT vs. surgery alone: 1.0 vs. 3.9, p = 0.037), whereas only the World Health Organization performance status (HR for grade 0 vs. grade 1 vs. grade >1: 1.0 (p = 0.022) vs. 1.2 (p = 0.640) vs. 7.7 (p = 0.008)) significantly influenced OS. CONCLUSIONS: MMHN is a rare tumor with a poor prognosis. Combination of surgery and PORT offers the best prospects for LRC but without improvement of OS. Due to potential toxicity of high-dose RT such treatment is indicated in patients in whom LRC outweighs the risks of serious adverse effects.

Proteolytic profile of cysteine proteases and inhibitors determines tumor cell phenotype in squamous cell carcinoma of the head and neck.

The hypothesis was tested that a specific pattern in the cysteine cathepsin/inhibitor ratio is associated with the development of more aggressive tumor cell phenotypes in squamous cell carcinoma of the head and neck (SCCHN). For this purpose commercially available ELISAs were used to determine the concentrations of cysteine cathepsins B and L and their inhibitors, stefins A and B, in cytosols of nontumorous mucosa and primary tumors from 92 patients. Using the stefin A concentration difference in matched pairs of tissue samples as a stratifying variable, 53 cases were found to be upregulated (higher concentrations in tumor samples than in nontumorous mucosa) and 39 cases downregulated. Disease recurrence was more frequent in the downregulated group than in the upregulated group (35.9% vs 11.3%, p=0.009), which resulted in significantly different 5-year disease-free survival rates (61.2% vs 88%, p=0.004). The consistency of these results was confirmed by repeating the analysis in an independent group of patients (the reference group). The presented results suggest that in patients with SCCHN, specific patterns in the proteolytic profile of cysteine proteases and their inhibitors are associated with the development of distinctly aggressive tumor cell phenotypes and are of prognostic value.