Chemosensory Functions After Glossectomy-A Cross-Sectional Pilot Study.

OBJECTIVE: To evaluate potential interactions and compensatory mechanisms of subjectively impaired taste function with ortho- and retronasal olfaction after glossectomy. STUDY DESIGN: In this cross-sectional pilot study, chemosensory functions were assessed in 25 patients with tongue carcinomas after glossectomy. The orthonasal-, retronasal-, and gustatory functions were tested with a mean time of 25 months after surgery with the Sniffin' Sticks odor identification test kit (ISST), the Candy Smell-27 test (CST-27) and the Taste strip test (TST). Visual analog scales (VAS) were additionally used for self-assessment of taste, flavor perception, and odor ranging from 0 (no perception) to 10 (excellent perception) and further correlated with our psychophysical evaluated outcome measures. RESULTS: The TST, ISST, and CST-27 tests revealed that only eight (32%) and 13 (52%) glossectomy patients had normal taste and orthonasal function, e 21 (84%) patients showed normal retronasal function. Importantly, neither extent of resection and reconstruction nor prior radiotherapy affected chemosensory functions. Contrary, 20 (80%) patients rated their taste and flavor perception as acceptable (VAS >5). Results of the TST, ISST, and CST-27 tests did not correlate with the equivalent self-assessments of taste (p = 0.260, r = 0.234), odor (p = 0.588, r = -0.114), and flavor (p = 0.728, r = 0.073) perception. CONCLUSION: There was a significant discrepancy between self-perception of taste and flavor and assessed gustatory function after glossectomy. A contribution of the intact retronasal olfactory system could be a possible explanation of our results. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:375-382, 2023.

Potential association of the prognostic index and survival in patients with p16-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma. METHODS: Patients treated with primary surgery from 2012 to 2019 with available preoperative (0-2 days) values of C­reactive protein and white blood cell counts needed for calculation of the PI, were included. Main outcome measures were overall survival (OS) and disease-free survival (DFS). The PI was dichotomized into low (PI = 0) and high (PI ≥ 1). RESULTS: In this study 36 patients were included. Average overall (OS) and disease-free survival (DFS) were 3.3 years (range 0.2-12.3 years) and 2.8 years (0.0-9.8 years), respectively. The overall mortality was 16.7% (n = 6) and a recurrent disease was observed in 30.6% of patients (n = 11). Low PI was associated with better overall survival (mean OS 10.1 ± 1.4 years, 95% confidence interval, CI 7.3-12.9 years vs. 1.9 ± 0.4, 95% CI 1.3-2.6 years, p < 0.01; mean DFS 8.5 ± 0.7 years, 95% CI 7.1-9.6 years vs. 1.0 ± 0.3 years, 95% CI 0.5-1.5 years, p < 0.01). CONCLUSION: The PI might be an easily obtainable outcome prognosticator in p16-positive oropharyngeal squamous cell carcinoma patients. Analyzing routinely obtained blood samples can contribute to identifying high-risk patients.

A prospective study of intraoperative assessment of mucosal squamous cell carcinoma margins in the head and neck.

BACKGROUND: In head and neck cancers, tumor margin assessment has important prognostic and therapeutic implications. Frozen section control of margins is commonly employed intraoperatively. However, this is not without limitations. The aim of this study is to determine whether intraoperative slicing of the whole specimen is feasible and what impact this may have on tumor margin assessment and the requirement for postoperative radiotherapy. METHODS: From September 2016 to August 2018, we recruited 22 patients as a pilot study looking at both the practicalities and the clinical relevance of whole margin tumor analysis intraoperatively. Our project is a prospective single arm study with historical controls. RESULTS: Forty-one percent of our patients required further intraoperative resection for close or involved margins. Seven of these patients who otherwise would have required adjuvant radiotherapy due to their margin status did not, after our intervention. CONCLUSIONS: We found that although requiring resources, this process was feasible without unduly increasing operative times and with potential patient benefit including reduced incidence of adjuvant radiotherapy.

Bacterial colonization of Montgomery salivary bypass tubes after hypopharyngeal reconstruction in head and neck cancer patients.

BACKGROUND: Hypopharyngeal reconstruction after salvage pharyngolaryngectomy results in high postoperative morbidity. The use of salivary bypass tubes can reduce pharyngocutaneous fistula (PCF) formation. The influence of bacterial colonization has not been described in literature. METHODS: Bacterial swipes from 26 consecutive patients reconstructed after laryngopharyngectomy in combination with Montgomery salivary bypass tubes (MSBT) were analyzed in regards to PCF formation. RESULTS: PCF occurred in 2 untreated primary and in 9 salvage laryngopharyngectomies, respectively. Bacterial colonization showed high rates of gram-negative pathogens and drug resistance to standard Ampicillin treatment. Type of bacteria was not associated with fistula formation. Antibiotic resistance was found in 6 out 11 patients (54%) with PCF. CONCLUSIONS: We identified high rates of antibiotic-resistant Gram-negative pathogens on MSBT. Although not statistically significant, PCF were found more frequently in drug-resistant patients. Bacterial colonization of hypopharyngeal reconstructions should therefore be taken into account for perioperative prophylaxis.

Pretreatment assessment of hematologic and inflammatory markers in adenoid cystic carcinoma: neutrophil/lymphocyte ratio is associated with multiple recurrences.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a rare entity of salivary gland cancer. Inflammatory and hematologic markers and their prognostic and predictive value have been intensively studied in several cancer entities. The aim of this study was to investigate the role of such markers in patients with ACC. STUDY DESIGN: This retrospective analysis investigated hematologic and inflammatory markers in patients with ACC in the period between the years 1996 and 2016. We assessed the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, cross-reactive protein and fibrinogen levels. A total of 28 to 31 patients were included, depending on the examined parameter. All markers were evaluated for their effects on outcome and prognostic value. RESULTS: Patients with an elevated preoperative NLR (>2) had a significantly higher multiple recurrence rate (44.4% vs 8.3%; P = .049). Other hematologic markers showed no significant effects on outcome. CONCLUSIONS: This study showed that the NLR may serve as a useful prognosticator for a high risk of multiple recurrences in patients with ACC.

Dysregulation of ß-catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck.

OBJECTIVE: The objective of this study was to determine the prognostic and predictive impact of ß-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Protein expression profiles of ß-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters. MAIN OUTCOME MEASURES: Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS). RESULTS: Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P = 0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P = 0.036). Conversely, low expression of ß-catenin (P = 0.025) and WISP1 (P = 0.037) revealed a better response to radiotherapy. CONCLUSION: Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.

Risk factors for acute unplanned tracheostomy during panendoscopy in HNSCC patients.

BACKGROUND: Despite of careful pre-operative risk evaluation some patients require an acute unplanned tracheostomy during panendoscopy. METHODS: Risk factors of patients requiring an unplanned tracheostomy during panendoscopy (n = 32) were compared to a control group with panendoscopy without tracheostomy (n = 180). RESULTS: 2131 panendoscopies for Head and Neck squamous cell carcinoma were performed at our Department between 2000 and 2014. Unplanned tracheostomies were necessary in 1.6% of all panendoscopies. Patients with laryngeal cancer (p = 0.001) or abnormal activated partial thromboplastin time (aPTT) (p = 0.03) had a statistically significant higher risk of unplanned tracheostomy. Regression analysis showed that patients with advanced laryngeal cancer had an almost 6 times higher risk for tracheostomy than patients with early stage oropharyngeal cancer. CONCLUSIONS: We identified abnormal aPTT and laryngeal carcinoma as significant predictors for unplanned tracheostomy during panendoscopy. The results of our study could improve preoperative risk evaluation in HNSCC patients.

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC. METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed. RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6). CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

BACKGROUND: The purpose of this study was to determine whether the expression of 15-lipoxygenase-1 (ALOX15) in primary tumour specimens predicts lymph node metastasis and subsequently clinical outcome in Merkel cell carcinoma (MCC) patients. METHODS: A retrospective medical chart review of 33 patients was performed between 1994 and 2014. Eleven out of 33 (33%) Patients with primary MCC stages I and II were categorised as group I. Twenty two out of 33 (67%) Patients with regional lymph node metastases and/or distant metastases were defined as group II. All available tumour samples were immunostained for ALOX15, Podoplanin and MCPyV large T-protein antibody. RESULTS: ALOX15 expression was observed in 19/23 (83%) primary tumour samples and in all lymph node metastasis. Primary tumours in patients with stage III and IV disease showed a higher expression rate of ALOX15 compared to patients with early stage disease (11/12 (92%) and 8/11 (73%), respectively). In group I, five patients (45%) were MCPyV positive, whereas in group II, 15 patients (68%) were MCPyV positive. The median lymphatic vessel density in ALOX15 negative group I primary tumour samples was lower compared to the median lymphatic vessel density in ALOX15 positive group I primary tumour probes (2.7 range, 1-4.3 vs 4.7 range, 4.0-7.3). Furthermore, all 17 samples of MCC metastases showed ALOX15 expression with a median lymphatic vessel density (not lymph node metastases) of 5.3 (range 2.0-7.3). CONCLUSION: In the current study, we were able to show ALOX15 expression in the primary MCC sample and the metastasis sample. Based on the findings of the current study, expression rate of ALOX15 in primary MCC and metastases is possibly linked to an increased lymphatic vessel density.

Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome.

BACKGROUND: The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors. METHODS: Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome. RESULTS: 41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002). CONCLUSIONS: To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.

ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinoma - a short report.

PURPOSE: Previously, the engulfment and cell motility 3 (ELMO3) protein has been reported to be involved in cell migration and cytoskeletal remodeling. As of yet, nothing is known about the role of ELMO3 in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses ELMO3 expression in postoperatively irradiated HNSCC patients and to evaluate a possible correlation between this expression and patient survival. METHODS: 125 postoperatively irradiated HNSCC patients were included in this study. ELMO3 expression was assessed using immunohistochemistry (IHC). The expression of ELMO3 in the respective HNSCC tumor tissues and its lymph node metastases was correlated with patient survival using Kaplan-Meier curve analyses. RESULTS: Through IHC, ELMO3 expression was detected in 71.2% of the HNSCC cases tested. We found significantly increased overall and disease-free survival rates and decreased recurrence rates in patients with no detectable ELMO3 expression. In reverse, we found that ELMO3 expression served as an independent marker for a decreased overall and disease-free survival. CONCLUSION: Our data indicate that in the surgically treated and postoperatively irradiated patients tested, ELMO3 expression serves as a predictive marker for reduced survival.

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy.

INTRODUCTION: HPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma. MATERIALS AND METHODS: In this prospective study, pretreatment tumor biopsies of patients with head and neck squamous cell carcinoma were taken during panendoscopy (2005 to 2008). All patients were treated with surgery and postoperative radiotherapy. After assessment of HPV and p16 status, protein expression profiles of the Sonic hedgehog-signaling pathway were determined by immunohistochemistry and tissue microarray analyses in 36 HPV negative tumor biopsies. Expression profiles of Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2 and Gli-3 were correlated with patients´ clinical data, local-control rate, disease-free as well as overall survival. Data from The Cancer Genome Atlas databank were used for external validation of our results. RESULTS: Gli-1 (p = 0.04) and Gli-2 (p = 0.02) overexpression was significantly linked to improved overall survival of HPV negative patients. Gli-2 (p = 0.04) overexpression correlated significantly with prolonged disease-free survival. Cox-multivariate analysis showed that overexpression of Gli-2 correlated independently (HR 0.40, 95% CI 0.16-0.95, p = 0.03) with increased overall survival. DISCUSSION: Gli-1 and Gli-2 overexpression represents a substantial prognostic factor for overall and disease-free survival in patients with locally advanced HPV negative head and neck cancer undergoing surgery and postoperative radiotherapy.

Minor salivary gland carcinoma: a review of 35 cases.

Minor salivary gland carcinomas represent a heterogeneous group of tumors with broad variation in clinical appearance and histopathology. Clinical data of patients with small salivary gland malignancies were collected from the medical records. Tissue microarray was constructed to determine the expression pattern of 24 proteins in 35 patients with minor salivary gland carcinomas. The choice of markers was based on involvement in neoangiogenesis, cell-to-cell contact, cell-cycle regulation and carcinogenesis. Protein expression data were correlated to patients' clinical data. Overexpression of patched (p = 0.046) and Smo (p = 0.032) was linked to a better overall survival and Glutathione S-transferase π overexpression was linked to prolonged disease-free survival (p = 0.005). Cox-1 (p = 0.035) and VEGFR2 (p = 0.009) were significantly linked to decreased survival for recurrent disease. Bcl-x (84 %), ß-catenin (87 %) and Cox-2 (87 %) were significantly overexpressed in minor salivary gland carcinomas. We have shown that Smo resulted in a better overall survival, whereas Gstπ in improved disease-free survival. VEGFR2 was a prognostic factor for survival after recurrence in patients with minor salivary gland carcinomas. Cyclooxygenase inhibitors and anti-Wnt-1 antibodies might be a potential therapeutic option in an adjuvant setting or for patients with unresectable tumors of the minor salivary glands.

Merkel cell carcinoma: Overall survival after open biopsy versus wide local excision.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with a dismal prognosis. METHODS: We conducted a retrospective medical chart review of patients with MCC who were initially diagnosed with an open biopsy (n = 30) or wide local excision (n = 24). RESULTS: Stages I, II, and III disease was found in 38%, 20%, and 16%, respectively. The 2-year and 5-year overall and disease-specific survival rates were 64.8% and 38.8% versus 45.2% and 26.4%, respectively. Cox regression multivariate model, including tissue sampling technique, re-resection, therapy modalities, pathological staging, and T and N classifications, showed that patients diagnosed initially with an open biopsy have significant worse overall (p = .014) and disease-free (p = .005) survival rates compared with patients who had a wide local excision. CONCLUSION: This study showed an improved overall survival in patients with MCC after wide local excision compared to open biopsy of the primary site at first diagnosis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1014-E1018, 2016.

Assessment of caroverine as a potential chemotherapeutical agent in HNSCC cell lines.

Since the prognosis of head and neck squamous cell carcinoma (HNSCC) still remains poor, identifying novel chemotherapeutic agents is of outmost importance. The anticancer potential of quinoxalines has been described in various tumor entities. Caroverine, also a quinoxaline derivative, has been shown to suppress tumor promotion factors. The aim of this study was to evaluate the effect of caroverine on HNSCC cell lines. The HNSCC cell lines SCC9, SCC25, CAL27, and FaDu were incubated with caroverine alone or in combination with cisplatin, 5-fluorouracil (5-FU) or cetuximab. Cell viability was measured using the CCK-8 assay. The murine 3T3 fibroblast cell line was used to address tissue specificity. Apoptosis was visualized by immunohistochemistry. Caroverine showed a dose-dependent growth inhibition in all cell lines, IC50 values ranged from 75.69 to 179.80 µM. This effect was increased when caroverine was combined with cetuximab or 5-FU. Immunohistochemistry displayed more apoptosis after caroverine treatment compared to controls. Furthermore, caroverine alone had no growth inhibitory effect on 3T3 cells. For the first time, this study provides evidence that caroverine may serve as a supportive drug in the treatment of HNSCC patients.

Management of Merkel cell carcinoma of unknown primary origin: the Vienna Medical School experience.

Merkel cell carcinoma is a rare, but highly aggressive skin tumor. We describe our single-institution experience with the diagnosis and treatment of Merkel cell carcinoma of unknown primary (MCCUP). We conducted a retrospective medical chart review of patients treated with MCCUP at the Vienna General Hospital between 2002 and 2011. Clinicopathologic variables and outcomes were analyzed. Of the entire cohort of 57 patients, 8 patients (14%) were diagnosed with MCCUP. Three patients presented with parotid gland involvement, four patients with positive inguinal lymph nodes and one with axillar lymph nodes. CK20 staining was positive in all tumor specimens, whereas MCPyV protein was positive in four out of six patients. The primary surgical modality in five cases was wide local excision. In one patient excisional biopsy was followed by re-resection. In one case only excisional biopsy was performed due to metastatic disease at first diagnosis. Two patients underwent concomitant parotidectomy and neck dissection, and four patients received adjuvant radiation therapy. Median recurrence-free survival was 20 months. Four patients died, three of disease and one of other cause. Recurrent disease was observed in two patients and treated with radiotherapy and chemotherapy. The 1- and 3-year overall survival rates were 87.5 and 37.5%, respectively. The 1- and 3-year disease-specific survival rates were 87.5 and 62.5%, respectively. Our study shows a poor outcome in patients with MCCUP, particularly in patients with node involvement of the trunk. We therefore suggest an aggressive and multimodal treatment approach for patients with MCCUP.

Prognostic significance of lymph node ratio in patients with Merkel cell carcinoma.

Merkel cell carcinoma is a rare and aggressive metastasizing tumor of the skin. Lymph node metastasis is a significant clinical prognostic factor for overall and disease-free survival in patients with Merkel cell carcinoma. A retrospective medical chart review of 12 Merkel cell carcinoma patients was performed. All patients received treatment at the Medical University of Vienna and underwent lymph node dissection between 1994 and 2013. The lymph node ratio was determined by dividing the total number of positive lymph nodes by the entire number of dissected lymph nodes. A positive lymph node ratio was defined as a number >0 and the negative lymph node ratio was defined by zero. The median follow-up was 44 months (range 4-92). A positive lymph node ratio (range 1.00-0.04) was found in 7 (58%) out of 12 patients of whom 5 (71%) died of disease. A negative lymph node ratio was found in 5 (42%) out of 12 patients of whom 2 (40%) patients died of disease. The disease-specific death rate was higher in patients diagnosed with a positive lymph node ratio compared to patients diagnosed with a negative lymph node ratio. Based on these preliminary findings, there might be a prognostic impact of lymph node ratio in patients suffering from Merkel cell carcinoma.