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Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common squamous cell carcinoma of the head and neck with no reliable diagnostic biomarkers. However, recent studies have shown that inflammation plays an essential role in tumor development, and several inflammation-based biomarkers have been shown to have prognostic value. This study aimed to investigate the auxiliary value of fibrinogen (FIB), fibrinogen degradation products (FDP), and lymphocyte/monocyte ratio (LMR) in LSCC diagnosis and prognosis. Methods: Clinical data from 218 patients recently diagnosed with LSCC and 207 diagnosed with benign laryngeal lesions (BLLs) were retrospectively reviewed. Potential diagnostic biomarkers were evaluated using univariate and multivariate analyses; receiver operating characteristic (ROC) curve analysis was used to identify cut-off values and diagnostic efficiency. Least absolute shrinkage and selection operator (LASSO) Logistic regression analysis was used to screen for independent risk factors to construct a diagnostic nomogram. The chi-squared test and Kaplan–Meier method were performed to investigate the correlation of clinicopathological characteristics and 3-year overall survival (OS) with FIB, FDP, and LMR in patients with LSCC. Results: FIB, FDP, and LMR levels were significantly different between the LSCC and BLL groups (P <.001), and all were independent risk factors for LSCC. The area under the ROC curve of the diagnostic nomogram was.894. Additionally, FIB, FDP, and LMR were correlated with some invasive clinicopathological features, and LMR ≥4.29 was associated with reduced OS (P =.038). Conclusion: FIB, FDP, and LMR demonstrated potential as biomarkers for the diagnosis and prognosis of LSCC; however, further studies are needed to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Objectives: Despite the increasingly modern surgical techniques in the oncology field, the factors that influence postoperative prognosis in patients with hypopharyngeal and laryngeal carcinoma (HLC) remain unclear. The study aimed to evaluate the factors influencing the prognosis of HLC patients with pathological diagnosis of squamous cell carcinoma, and the findings are intended to direct follow-up management strategies. Methods: A retrospective cohort study was performed. The study population included 407 postoperative patients with HLC from 2011 to 2015. Univariate and multivariate analyses were used to examine the prognostic factors identified. Results: Based on univariate analysis results, smoking and alcohol history, tumor differentiation, preoperative radiotherapy, primary tumor sites, flap reconstruction, lymph node invasion (LNI), and preoperative albumin levels (PAL) significantly affects the prognosis of HLC patients (P <.05). Meanwhile, multivariate analysis revealed that smoking pack-year (OR = 1.002, 95% CI = 1.001 ∼ 1.003), primary tumor sites (OR = 6.241, 95% CI = 1.715 ∼ 18.433), LNI (OR = 2.869, 95% CI = 1.095 ∼ 8.743), and PAL (OR =.020, 95% CI =.004 ∼ 0.104) were associated with complications. Tumor differentiation (OR = 0.650, 95% CI =.383 ∼ 0.855), primary tumor sites (OR = 12.392, 95% CI = 3.290 ∼ 26.679), LNI (OR = 16.323, 95% CI = 2.726 ∼ 47.729), preoperative radiotherapy (OR = 9.300, 95% CI = 3.182 ∼ 27.181), and PAL (OR =.321, 95% CI =.141 ∼.732) were associated with overall survival rates. Conclusion: Smoking and alcohol history, tumor differentiation, LNI, primary tumor sites, flap reconstruction, PAL, and preoperative radiotherapy are crucial factors that influence the postoperative prognosis of patients with HLC. In addition, a monogram of five factors was established to predict the survival rates of HLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: We are going to highlight new prognostic and predictive factors, CD44, PDL1, and ATG7, in surgical samples from patients with laryngeal squamous cell carcinoma (LSCC). Immunohistochemical analysis with primary antibodies anti-CD44, PD-L1 and ATG7 was performed using the tissue microarray (TMA) technique. Considering follow-up data, the 5-year disease-free survival (DFS) was 85.71% and 36% for CD44-negative and -positive tumors. The 5-year DFS was 60% and 33.33% for negative and positive PDL1 tumors, respectively. At the follow-up, 5-year DFS was 58.06% and 37.50% for negative and positive ATG7 tumors. We focus on the new prognostic and predictive factors CD44, PDL1, and ATG7 in our study of surgical samples of patients with laryngeal squamous cell carcinoma (LSCC) using tissue microarray (TMA). Thirty-nine previously untreated patients affected by laryngeal carcinoma who then underwent surgical treatment were considered in this retrospective study. All surgical specimens were sampled, embedded in paraffin blocks, and stained with hematoxylin and eosin. A representative sample of the tumor was chosen and transferred into a new block of paraffin, the recipient block, to perform immunohistochemical analysis with the primary antibodies anti-CD44, PD-L1, and ATG7. At follow-up, 5-year disease-free survival (DFS) for negative and positive tumors was determined as 85.71% and 36% for CD44, 60% and 33.33% for PDL1, and 58.06% and 37.50% for ATG7, respectively. Multivariate analysis revealed that CD44 expression is an independent predictive factor of low-grade tumors (p = 0.008), lymph node metastasis at the time of diagnosis, and AGT7 negativity. Thus, CD44 expression is a potential marker for more aggressive forms of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study is the first attempt to investigate the tumor–stroma ratio in a series of laryngeal basaloid squamous cell carcinomas (SCCs), comparing them with a group of stage-matched conventional SCCs, in both preoperative and surgical specimens. This study's aim was to ascertain the biological aggressiveness of laryngeal basaloid SCCs and to investigate any possible role of stromal-related features in such a clinical behavior. The tumor–stroma ratio, evaluated in laryngeal biopsies and in the entire excised tumor, displayed a prognostic effect in terms of reduced disease-free survival in conventional SCC cases but not in basaloid ones. Basaloid squamous cell carcinoma (BSCC) is a subtype of squamous cell carcinoma (SCC) associated with a poor prognosis. Tumor–stroma ratio (TSR) has been introduced as a prognostic feature in many solid tumors. TSR was investigated in a series of laryngeal BSCCs and compared with a group of stage-matched conventional SCCs (cSCCs), in both preoperative and surgical specimens, with the intent of ascertaining the more aggressive behavior of BSCC and verifying the presence of stromal-related causes. A series of 14 consecutive laryngeal BSCCs and a control group of 28 stage-matched conventional cSCCs were analyzed. A higher nodal metastasis presence was found in BSCCs (57.1% vs. 28.6%). The recurrence rate was 33.5% and 63.6% in the cSCC and BSCC groups; disease-free survival (DFS) was higher, though not significantly, in patients with cSCC. TSR, large cell nests, and tumor budding showed a moderate to very good agreement, and stroma type a good to very good agreement between biopsies and surgical specimens in the cSCC group. In the BSCC group, agreement was poor to very good for TSR and stroma type, and good to very good for large cell nests and tumor budding. Age was the only feature significant in predicting recurrence in the BSCC group (p = 0.0235). In cSCC, TSR low/stroma rich cases, when evaluated on biopsies or surgical specimens, were associated with lower DFS (p = 0.0036; p = 0.0041, respectively). Laryngeal BSCCs showed a lower DFS than cSCCs, even if statistical significance was not reached. TSR, evaluated in laryngeal biopsies and excised tumors, was prognostic in terms of DFS in cSCC but not in BSCC cases. [ABSTRACT FROM AUTHOR]

Simple Summary: The central compartment of the neck is not cleared during a comprehensive neck dissection, which usually encompasses neck levels I to V. When involved by clinically evident lymph node metastases, central neck compartment dissection is mandatory; on the other hand, precise indications regarding the elective surgical management of occult lymph node metastases at this level are still a matter of debate. Laryngeal and hypopharyngeal squamous cell carcinomas can spread to regional lymph nodes located in the central neck compartment. This anatomic region contains the laryngeal nerves, the thyroid, and parathyroid glands, and its boundaries are represented by major vessels. This paper will focus on relevant clinical aspects that must be considered in order to formulate a judicious balance between the probability of dealing with occult disease and the possibility of being confronted with unnecessary iatrogenic risks. Metastatic lymph node involvement represents the most relevant prognostic factor in head and neck squamous cell carcinomas (HNSCCs), invariably affecting overall survival, disease-specific survival, and relapse-free survival. Among HNSCCs, laryngeal and hypopharyngeal cancers are known to be at highest risk to metastasize to the central neck compartment (CNC). However, prevalence and prognostic implications related to the CNC involvement are not well defined yet, and controversies still exist regarding the occult metastasis rate. Guidelines for the management of CNC in laryngeal and hypopharyngeal cancers are vague, resulting in highly variable selection criteria for the central neck dissection among different surgeons and institutions. With this review, the authors intend to reappraise the existing data related to the involvement of CNC in laryngeal and hypopharyngeal malignancies, in the attempt to define the principles of management while highlighting the debated aspects that are lacking in evidence and consensus. Furthermore, as definition and boundaries of the CNC have changed over the years, an up-to-date anatomical–surgical description of the CNC is provided. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration.Methods: We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples.Results: We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module 'cyan', TARS in the module 'darkorange', and COPB2 and RYK in the module 'lightyellow' showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients.Conclusions: Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes. [ABSTRACT FROM AUTHOR]

Objective: Sex-determining region-Y-related high-mobility-group box 4 (SOX4) is associated with the metastasis and prognosis of many cancer types. However, studies on the role of SOX4 in laryngeal squamous cell carcinoma (LSCC) are few, and hence the mechanism is unclear. Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the plasticity and motility required for tumor progression and metastasis. This study aimed to analyze the relationship between SOX4 and EMT, and their relationship with clinicopathological factors and related prognosis.Methods: Immunohistochemical staining was used to detect the positive expression of SOX4 protein, EMT-related transcription factor protein, and related marker protein in 127 LSCC tissue samples. At the same time, data on various parameters of clinical pathology and postoperative survival were collected.Results: The positive expression rate of SOX4 and Slug in LSCC was related to pathological differentiation, Lymph node metastasis (LNM), and pathological TNM of a tumor. The expression rates of ZEB1, E-cadherin, N-cadherin, and β-catenin in LSCC correlated with LNM and pTNM. The expression of SOX4, combined expression of SOX4 and ZEB1, and LNM were independent prognostic factors for the total survival time of patients with LSCC.Conclusions: In summary, SOX4 was vital in the LSCC EMT process, which might be mediated by transcription factor ZEB1. SOX4 and ZEB1 might serve as potential biomarkers of metastasis and prognosis, as well as promising therapeutic targets of LSCC. [ABSTRACT FROM AUTHOR]

Objective: It remains elusive which factors may influence the morbidity and mortality of lung metastasis (LM) in Laryngeal Squamous Cell Carcinoma (LSCC) patients. The aim of the present study was to investigate factors influencing LM and the survival outcomes of LSCC patients with LM.Methods: We identified 10,935 patients with LSCC from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Multivariate logistic regression analysis was used to determine the factors associated with the presence of LM. Multivariate cox regression analysis was used to identify covariates associated with increased all-cause mortality in patients with LM.Results: Among 10,935 patients with LSCC, 232 (2.12%) patients had LM. The median survival time of patients with LM was 8 months, and 8.37% of patients survived after 3 years. Patients with age ≥ 60 years old, unmarried status, supraglottis, overlapping lesion of larynx, subglottis, pathological grade III, T4 stage, N1 stage, N2 stage, N3 stage and bone, brain or liver metastases were more likely to have LM. Survival analysis showed that chemotherapy and radiotherapy suggested better survival of LSCC patients with LM while pathological grade IV was associated with an increased all-cause mortality.Conclusion: The incidence of LSCC patients with LM varied by age, married status, and tumor subtypes. LSCC patients with LM had poor survival, and only 8.37% of patients survived after 3 years. However, chemotherapy and radiotherapy were found as independent favorable prognostic factors for survival. [ABSTRACT FROM AUTHOR]

Background: Terminal differentiation-induced ncRNA (TINCR) plays an essential role in epidermal differentiation and is involved in the development of various cancers.Methods: qPCR was used to detect the expression level of TINCR in tissues and cell lines of laryngeal squamous cell carcinoma (LSCC). The potential targets of TINCR were predicted by the bioinformation website. The expression of miR-210 and BTG2 genes were detected by qPCR, and the protein levels of BTG2 and Ki-67 were evaluated by western blot. CCK-8 assay, scratch test, and transwell chamber were used to evaluate the proliferation, invasion, and metastasis ability of LSCC cells. The relationships among TINCR, miR-210, and BTG2 were investigated by bioinformatics software and luciferase reporter assay. The in vivo function of TINCR was accessed on survival rate and tumor growth in nude mice.Results: We used qRT-PCR to detect the expression of TINCR in laryngeal squamous cell carcinoma (LSCC) tissues and cells and found significantly lower levels in cancer tissues compared with adjacent tissues. Additionally, patients with high TINCR expression had a better prognosis. TINCR overexpression was observed to inhibit the proliferation and invasion of LSCC cells. TINCR was shown to exert its antiproliferation and invasion effects by adsorbing miR-210, which significantly promoted the proliferation and invasion of laryngeal squamous cells. Overexpression of miR-210 was determined to reverse the tumour-suppressive effects of TINCR. BTG2 (anti-proliferation factor 2) was identified as the target gene of miR-210, and BTG2 overexpression inhibited the proliferation and invasion of LSCC cells. BTG2 knockdown relieved the inhibitory effects of TINCR on the proliferation and invasion of LSCC. Finally, TINCR upregulation slowed xenograft tumour growth in nude mice and significantly increased survival compared with control mice.Conclusion: The results of this study suggest that TINCR inhibits the proliferation and invasion of LSCC by regulating the miR-210/BTG2 pathway, participates in cell cycle regulation, and may become a target for the treatment of LSCC. [ABSTRACT FROM AUTHOR]

Background: Expression of the mu-opioid receptor (MOR) is associated with poor long-term outcomes in various types of cancer. The association between MOR expression and clinical outcomes in laryngeal squamous cell carcinoma (LSCC) is not clear.Methods: This retrospective study included patients who underwent laryngectomy for LSCC. The expression pattern of the MOR protein and OPRM1 gene in tumours and corresponding adjacent non-carcinoma specimens was measured. Propensity score matching was used to minimise bias. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were intraoperative sufentanil consumption, grade of surgical complications according to the Clavien-Dindo classification, and hospital length of stay.Results: A total of 207 LSCC patients were enrolled. After propensity score matching, there was a significant difference in DFS between groups at 1, 3, and 5 yr (60.2% vs 81.2%, P=0.019; 39.4% vs 50.2%, P=0.026; 37.5% vs 42.5%, P=0.023, respectively) in patients with high MOR expression. The OS rates at 1, 3, and 5 yr were significantly lower in the high MOR expression group (81.2% vs 93.2%, P=0.027; 57.7% vs 78.3%, P<0.001; 42.5% vs 60.3%, P<0.001, respectively). The multivariate analysis indicated that high MOR expression was associated with worse DFS and OS (hazard ratio: 1.52, 95% confidence interval: 1.07, 2.25, P=0.034; hazard ratio: 1.42, 95% confidence interval: 1.17, 2.34, P=0.032).Conclusion: High MOR expression may be associated with poor prognosis in patients with LSCC, suggesting that MOR could be used as a valuable molecular biomarker to predict prognosis of LSCC patients. [ABSTRACT FROM AUTHOR]

Background: Several recent studies have indicated that the lymph node ratio (LNR) is an independent prognostic factor for laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). The purpose of this paper is to assess the prognostic value of LNR and explore appropriate cutoff values by conducting a systematic review and meta-analysis. Methods: Pubmed, Embase (via Ovid), and Cochrane library were systematically searched for studies on the prognostic value of LNR in LHSCC up to October 31, 2019. Then, Literature review, data extraction, and quality assessment of eligible studies were performed by two independent reviewers back-to-back. Lastly, Stata 14.0 software was hired to conduct a meta-analysis. Results: A total of 445 articles were retrieved, and 13 studies published in English between 2013 and 2019 were included after the title/abstract and full-text screening. Among the 13 studies contributed to 4197 patients, seven studies were about hypopharyngeal squamous cell carcinoma (HPSCC), four studies about laryngeal squamous cell carcinoma (LSCC), and the remaining two studies about LHSCC. The meta-analysis results showed that shorter overall survival (OS) (HR 1.49; 95%CI: 1.18 to 1.88), disease-specific survival (DSS) (HR 1.66; 95%CI: 1.32 to 2.07) and disease-free survival (DFS) (HR 2.04; 95%CI: 1.54 to 2.71) were significantly correlated with a higher LNR in a random-effect model. The cutoff values of eligible studies were varied from 0.03 to 0.14, and the lowest significant LNR was 0.044. Conclusion: LNR is a valuable prognostic factor in the survival of LHSCC and may be used to improve the tumor staging systems, which, however, requires the solid support of more high-quality studies. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors. Objective: The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value. Materials and methods: We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers. The ROC curve was carried out to determine diagnostic accuracy. Results: We observed that serum miR-632 levels were upregulated in LSCC patients compared with healthy volunteers (p <.01). Subsequent results from ROC indicated that high sensitivity and specificity of serum miR-632 for diagnosing LSCC (area under the curve 0.8828). In addition, it was found that high expressions of serum miR-632 were significantly associated with advanced N stage (p =.020), histological grade (p =.001), and TNM stage (p =.014). Furthermore, patients with higher serum miR-632 expression had a shorter OS and DFS time than those with lower serum miR-632 levels. Conclusion: Our data revealed that serum miR-632 may be a potential noninvasive biomarker which may become a potential diagnostic and prognostic biomarker for LSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: Human papillomavirus (HPV) can be detected in approximately 25% of squamous cell carcinomas (SCC) of the larynx and hypopharynx. Though HPV is associated with improved survival and disease control in patients with oropharyngeal SCC, the role of HPV as a marker of favorable treatment outcomes in laryngeal and hypopharyngeal cancer is unclear.Materials and Methods: Patients treated for laryngeal or hypopharyngeal SCC were reviewed. HPV status detected by p16 and/or HPV DNA PCR were abstracted from the medical record. A subset of samples (stage III-IV treated with primary radiotherapy) was retrospectively tested for p16 and HPV DNA. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were determined and compared between HPV-positive (p16+, PCR+ or both) and HPV-negative (p16- or PCR-) patients.Results: In total, 279 patients were identified, 94 of which were tested for HPV. Eighty-two (87%) were negative and 12 (13%) were positive for HPV. At 3 years, there were no significant differences in OS (72% v. 83%), DFS (60% v. 71%) and LRC (80% v. 89%). Performance status, smoking history and stage predicted for OS, while performance status and stage predicted for DFS. Analysis of patients treated with primary radiotherapy revealed non-significantly higher rates of laryngeal preservation at 3 years (75% v. 100%).Conclusion: HPV was detected in 13% of tested laryngeal/hypopharyngeal cancers. HPV does not appear to significantly impact survival or disease control in patients with SCC of the larynx or hypopharynx. Non-significant improvements in laryngeal preservation were observed in HPV-positive patients. [ABSTRACT FROM AUTHOR]

Background: Neck lymph node status is the chief prognostic index in patients with head and neck squamous cell carcinoma (SCC), yet the management of a clinically negative neck in this setting is still controversial, especially in patients with laryngeal SCC (LSCC). Objectives: To evaluate the efficacy of selective neck dissection (SND) to control occult disease in patients with LSCC and clinically negative (cN0) necks. Materials and methods: Medical records of 1476 patients with cN0 LSCC were analyzed. In conjunction with primary treatment, 126 (8.5%) underwent at least unilateral elective neck dissection, whereas most 1350 (91.5%) followed a wait-and-see protocol. Prognostic significance was indicated by the Kaplan–Meier survival estimates. Results: The rate of occult neck disease was 15%. Five-year overall and disease-free survival rates were 74.4% and 66.7%, respectively. Prognosis was closely related to T stage, preoperative tracheotomy, and postoperative recurrence. There was no significant correlation with age, sex, or preoperative neck dissection; but in patients with supraglottic LSCC, the relation between prognosis and preoperative neck dissection was significant, with fewer neck and local recurrences than the wait-and-see group (p <.05). Conclusions and significance: Selective neck dissection is serving as an accurate prognostic tool in patients with supraglottic laryngeal cancers. [ABSTRACT FROM AUTHOR]

Background: Expression of the epidermal growth factor receptor (EGFR) and human papillomavirus (HPV) DNA can serve as independent prognostic factors in squamous cell carcinoma (SCC) of the larynx. EGFR correlation with the course of disease and its effect on survival makes EGFR expression a negative prognostic factor, whereas HPV DNA is a positive prognostic factor. Aim: To assess the association of EGFR expression with clinical outcome of laryngeal HPV SCC. Materials and methods: This retrospective study included 196 SCC patients operated on at the Department of ENT, Head and Neck Surgery, Split University Hospital Center in Split, Croatia, between 1 January 2000 and 31 December 2009. Results: The association of HPV infection and EGFR expression was found to be statistically significant, and so was the difference in survival between patient groups with different HPV to EGFR expression ratio. Conclusions: The group of laryngeal HPV SCC patients with increased EGFR expression had shorter survival, confirming EGFR as a major component in predicting patient prognosis and survival. Significance: This article confirms the importance of EGFR expression as a biomarker in laryngeal SCC. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is rare in the young. Objectives: We characterized the clinical behavior of LSCC and assessed the presentation of second primary tumors (SPCs) in this patient population. Materials and methods: Data from the Finnish Cancer Registry (FCR) were used to identify an epidemiological series of LSCC patients diagnosed at the age of 40 years or under, during 1953-2012 in Finland. Data regarding primary treatment, survival, and SPCs were available. To further characterize the comorbidity and lifestyle factors of young patients with LSCC, institutional data were collected of patients treated at the Helsinki University Hospital during 1967-2012. Results: We identified 151 patients, with a mean follow-up of 252 months. The 10-year overall survival (OS) was 75% and the disease-specific survival was 84%. SPCs were diagnosed in 26% (n = 39), with a median delay of 28 years. Of the 35 patients in the institutional series from Helsinki, 22 (63%) were current or former smokers. LSCC recurred in 28% of patients. Conclusions and Significance: The delay to SPCs in young patients was significantly longer compared with the general LSCC population. As factors underlying this phenomenon cannot be identified by this retrospective study, further studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Open laryngeal function-preserving surgery is a common therapeutic strategy for Chinese laryngeal squamous cell carcinoma (LSCC) patients. Objectives: To explore the fundamental clinical characteristics and survival prognostic factors of LSCC patients treated with open laryngeal function-preserving operations. Material and methods: about a total of 659 LSCC patients undergoing open laryngeal function-preserving operations were retrospectively reviewed. Kaplan-Meier method, Log-rank test and Cox regression model were performed in survival analyses. Results: About 612 patients were glottic cancer, followed by 44 cases in supraglottis and 3 cases in subglottis. The number of patients in stage T1, T2, T3 and T4 was 190, 365, 100 and 4, respectively. Nineteen patients had positive cervical lymph nodes. The 5-year overall survival, disease-free survival and disease-specific survival rates were 90.1, 84.9 and 90.7%, respectively. T stage and second primary tumour were independent factors predicting overall survival, while T stage and pathological differentiation were independent risk factors for tumour recurrence and progression. Conclusions and significance: Open laryngeal function-preserving surgery is a crucial therapeutic strategy for Chinese patients with early and, in some cases, advanced-stage LSCC. Early diagnosis and therapy and sufficient and safe surgical margins are key to improving the survival rate and reducing the risk of relapse in LSCC patients. [ABSTRACT FROM AUTHOR]

Background: T3 supraglottic laryngeal carcinoma (LC) is a common advanced laryngeal cancer. Objective: This study was conducted to assess the clinical results of pathological T3 (pT3) supraglottic LC patients who were amenable to laryngectomy treated with primary surgery and postoperative therapy. Methods: Retrospective review of 202 pT3 cases of supraglottic laryngeal squamous cell carcinoma. Results: The five-year cancer specific survival (CSS) rate was 63.7% and the overall survival rate (OS) was 62.8%. For T3 supraglottic patients who underwent total laryngectomy, the five-year disease-free survival (DFS) was 51.8%, and the CSS was 62.5%. For patients who underwent partial laryngectomy, the five-year DFS was 72.2%, and the CSS was 79.0%. High lymph node and stage status are predictors of mortality for these patients. No difference was found in the DFS and CSS rates between patients with negative margins and those with positive margins following postoperative radiotherapy and chemotherapy. Conclusion: Surgical treatment of T3 supraglottic LC patients achieved satisfactory results. Postoperative radiotherapy and chemotherapy are an effective method of treatment for T3 supraglottic LC patients, especially for those with a positive margin. [ABSTRACT FROM AUTHOR]

Background: The lack of standardized treatment is problematic in laser surgery for laryngeal cancer, and may result in an increased recurrence rate. This study analyzed the prognosis of early laryngeal carcinoma after different types of cordectomy with laser surgery. Methods: A cohort of 818 patients with stage Tis or T1 primary early glottic squamous cell carcinoma treated with CO2 laser surgery was retrospectively analyzed. Results: Of the 818 patients, According to the Kaplan-Meier method, the rate of 5-year overall survival was 92.8%, and the rates for 5-year disease-specific survival and 5-year locoregional control were 96.9% and 91.3%, respectively. Among the T1 patients, type II cordectomy with laser surgery had a significant impact on the 5-year locoregional control rate, but no obvious impact on the 5-year overall survival rate. Conclusions: There must be sufficient depth and extent of excision in T1 patientsand in early carcinoma especially those with possible microinvasive carcinoma [ABSTRACT FROM AUTHOR]

Objectives: To assess five-year local control and ultimate local control rates of patients treated for locally advanced T3–4 glottic carcinoma with surgery only, radiotherapy only, or surgery plus radiotherapy. Cancer-specific survival, overall survival and rates of malignancy development were also assessed. Methods: A retrospective review was conducted on patients from 1967 to 2015, with analysis of local control, ultimate local control, overall survival and cancer-specific survival performed using Kaplan–Meier and Cox regression. Results: Of 169 eligible patients, the majority (59 per cent) were treated with surgery plus radiotherapy, with laryngectomy being the most common surgical procedure. Local control and ultimate local control rates were higher with surgery only (94.1 per cent) and surgery plus radiotherapy (87.9 and 86.8 per cent respectively), compared to radiotherapy only (46.8 and 52.4 per cent) (both p < 0.001). Cancer-specific survival, overall survival and malignancy development did not differ between groups. Conclusion: Surgery, with or without radiotherapy, offers significantly higher five-year local control and ultimate local control for patients with advanced glottic carcinoma, compared to radiotherapy only. [ABSTRACT FROM AUTHOR]

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer.Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015.Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p=0.004). In multivariate analysis, age <70years (p=0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p=0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer.Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis. [ABSTRACT FROM AUTHOR]

Background:The expression and function of androgen receptors (AR) and estrogen receptor alpha (ER-ɑ) in laryngeal squamous cell carcinoma (LSCC) have remained controversial for decades. Prolactin receptor (PRLR) is a sex-related hormone, that has been rarely documented in terms of expression or function compared with data on other hormone receptors in laryngeal carcinoma. Methods:This study reports on immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis of tumour tissue and adjacent normal tissue in 96 patients with LSCC (82 males and 14 females). The expression levels of the receptors were related to clinicopathologic parameters and survival data. Results:At both protein and mRNA levels, the expression level of AR, ER-ɑ, and PRLR was much higher in LSCC than in adjacent normal tissues (p < .05). Among them, higher PRLR expression in tumour tissues tended to have a significantly poorer survival rate (p = .03) for patients with LSCC. Furthermore, higher expression of ER-ɑ in tumours was correlated with higher expression level of PRLR (r = .823,p = .03). Conclusion:The findings of this study indicate that the sex-related hormone receptors play an important role in the development of LSCC. The PRLR represents a novel prognosticator, because of its negative effect on survival and its interaction with ER-ɑ. [ABSTRACT FROM PUBLISHER]

Background: Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients.Methods: In an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693-704, 2006).Results: The evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82-1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04-3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21-45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP.Conclusions: T4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma of the head and neck (HNSCC) represents an array of disease processes with a generally unfavorable prognosis. Inflammation plays an important role in tumor development and response to therapy. We performed a retrospective analysis of HNSCC patients to explore the relationship of the lymphocyte and neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR) overall survival (OS), cancer-specific survival (CSS), local control (LC) and distant control (DC).Materials/methods: All patients received definitive treatment for cancers of the oropharynx or larynx between 2006-2015. Neutrophil and lymphocyte counts were collected pre-, during-, and post-treatment. The correlations of patient, tumor, and biological factors to OS, CSS, LC and DC were assessed.Results: 196 patients met our inclusion criteria; 171 patients were Stage III or IV. Median follow-up was 2.7 years. A higher neutrophil count at all treatment time points was predictive of poor OS with the pre-treatment neutrophil count and overall neutrophil nadir additionally predictive of DC. Higher pre-treatment and overall NLR correlated to worse OS and DC, respectively.Conclusion: A higher pre-treatment neutrophil count correlates to poor OS, CSS and DC. Lymphocyte counts were not found to impact survival or tumor control. Higher pre-treatment NLR is prognostic of poor OS. [ABSTRACT FROM AUTHOR]

Introduction: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes.Materials and Methods: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test.Results: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%.Conclusion: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age. [ABSTRACT FROM AUTHOR]

Objective: Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC).Methods: We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count.Results: By defining the platelet count 250.05×109/L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n=378, 45.9%), and those with a low platelet count (n=446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P=0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P=0.085).Conclusion: Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs).Methods: This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS).Results: The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS.Conclusions: For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy of concurrent chemoradiotherapy (CCRT) with daily low-dose cisplatin (CDDP) plus weekly docetaxel (DTX) for patients with T2N0 glottic cancer.Methods: Between January 2004 and December 2013, 62 treatment-naive patients with histologically proven T2N0 glottic cancer were treated with concurrent chemoradiotherapy. Radiation therapy (RT; 2 Gy daily fractions up to a total dose of 66 Gy) was administered in combination with daily low-dose CDDP (6 mg/m2, five times a week), plus weekly DTX (10 mg/m2) for up to 4 weeks from the commencement of RT.Results: Median duration of follow-up was 70 months. The actuarial 3-year and 5-year overall survival rates were 95% and 93%. The 3-year and 5-year cause-specific survival rates were both 100%. The actuarial 3-year and 5-year local control rates were 94% and 94%, respectively. Hematologic toxicity (neutoropenia of severity ≥ Grade 3) was observed in 8% of the patients, and non-hematologic toxicity (radiation mucositis of severity ≥ Grade 3) developed in one patient (2%). Radiation dermatitis of severity ≥ Grade 3 and laryngeal necrosis developed in one patient.Conclusion: CCRT with weekly DTX and low-dose CDDP appears to be a practical and safe modality and is expected to improve local control.Trial Registration: UMIN000025046 . Registered 1 October 2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the contribution of SHISA3 promoter methylation to laryngeal squamous cell carcinoma (LSCC). SHISA3 promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of the SHISA3 promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase in SHISA3 methylation in LSCC tissues compared with corresponding nontumor tissues P=4.58E-12. The qRT-PCR results show a significant association between SHISA3 methylation and expression in LSCC P=1.67E-03. In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest that SHISA3 promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rank P = 0.024; HR = 2.71; 95% CI = 1.024–7.177; P = 0.047). The results indicate that SHISA3 promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC. [ABSTRACT FROM AUTHOR]

Objective: After horizontal supraglottic partial laryngectomy, patients have an increased risk of dysphagia as they are not able to close the laryngeal entrance during swallowing, especially if the surgical defect of the tongue base has increased. There is no investigation that studies risk factors for impaired swallow function, or that predicts postoperative swallow outcomes based on radiologically determined tumor dimensions. The present study investigated the impact of the tongue base tumor extension (determined by CT scan in patients undergoing partial laryngectomy) on the recovery rate of swallow function. Methods: The retrospective study in a tertiary hospital between 2000 and 2015 included all patients who underwent open horizontal supraglottic partial laryngectomy due to oropharyngeal cancer of the tongue base, or supraglottic laryngeal cancer with tongue base infiltration. All clinicopathological data were collected. The dimension of tongue base infiltration was measured using CT scan. Swallow function was recorded by Fiberoptic Endoscopic Evaluation of Swallowing and determined by evaluating both the duration until nasogastric tube removal and changing of the cuffed tracheostomy tube for an uncuffed speech cannula. Results: The study included 26 patients (44-76 years, median 59 years). The clinical tumor (cT) classification included cT2 and cT3, while the pathologic tumor (pT) classification included pT2 and pT3 in 90% and pT1 and pT4 in 10% respectively. The duration until using the speech cannula was not associated with clinicopathological data, including the investigated radiologic tumor dimensions (biggest tumor diameter, tongue base infiltration depth, width, height, area and volume). The duration until nasogastric tube removal was significantly associated with the tongue base infiltration width (p=0.012), height (p=0.026) and area (p<0.0001). The patients were divided into two groups according to the median tongue base infiltration area estimated as 6.20cm(2). In patients <6.20cm(2), 50% of the nasogastric tubes were removed after 4 days (95% CI 0-8.6 days) and in patients ≥6.20cm(2), 50% were removed after 22 days (95% CI 6.8-37.2 days; p<0.0001). Conclusion: The postoperative swallow function after open horizontal supraglottic partial laryngectomy depends on the tumor extension of the tongue base. The tongue base infiltration area is a useful tool for surgical planning as it can be used to predict postoperative swallow function. In foreseeably permanent dysphagia, as well as permanent and necessary tracheotomy tube cuffs after organ-preserving surgery, alternative therapy methods should be particularly preferred as the primary chemoradiation. [ABSTRACT FROM AUTHOR]

Objective:To evaluate the clinical and histopathological factors affecting the prognosis of patients with squamous cell locoregional advanced laryngeal cancer.Methods:A retrospective chart review was conducted of 121 patients with locoregional advanced laryngeal cancer, primarily treated with surgery from 2007 to 2011. Disease-free survival and overall survival rates were analysed as oncological outcomes. Prognostic variables, namely gender, pharyngeal invasion, pathological assessment of tumour and nodal stage, adjuvant therapy, margin status, nodal extracapsular extension, tumour differentiation, lymphovascular and perineural invasion, and predominant growth pattern, were also analysed.Results:One-year and three-year disease-free survival rates were 81.3 per cent and 63.5 per cent, respectively. One-year and three-year overall survival rates were 88.3 per cent and 61.4 per cent, respectively. Multivariate analysis showed that nodal extracapsular extension (p < 0.05) and an infiltrative growth pattern (p < 0.05) were associated with disease progression. Nodal extracapsular extension (p < 0.05) was associated with higher mortality.Conclusion:Nodal extracapsular extension and an infiltrative growth pattern were the main prognostic factors in locoregional advanced laryngeal cancer. The presence of pharyngeal invasion, pathologically confirmed node-positive stage 2–3 disease, close or microscopic positive margins, and lymphovascular and perineural invasion have a negative impact on prognosis. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have demonstrated that aberrant Kif2a expression is associated with tumor aggressiveness and poor prognosis in various human cancers. However, the clinicopathological significance of Kif2a in laryngeal squamous cell carcinoma (LSCC) is unknown. The aim of this study is to analyze the prognostic significance of Kif2a, alone and in combination with Ki67 protein expression, in LSCC patients.Methods: We examined the expression status of Kif2a and Ki67 protein in 165 laryngeal tissues (137 primary tumors and 28 cases of matched normal surgical margins) by immunohistochemistry (IHC) analysis using tissue microarrays.Results: We found that expression correlated with clinical parameters and overall survival (OS). Our results revealed that Kif2a and Ki67 protein expression was significantly higher in cancerous tissues compared to normal surgical margins. High Kif2a protein expression (Kif2a+) was significantly associated with tumor stage (P=0.026) and cervical lymph node metastasis (P=0.034). A significant correlation between Kif2a and Ki67 protein expression was observed (P=0.040). Multivariate analysis revealed that patients with Kif2a+ (hazard ratio [HR] 3.640, 95% confidence interval [CI] 1.253-10.570; P=0.018) and high Ki67 (Ki67+) expression (HR 3.086, 95%CI 1.016-9.371; P=0.047) had poor OS.Conclusion: We speculate that Kif2a and Ki67 can be used as prognostic markers for LSCC patients. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study. In vitro studies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P<0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test, P<0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression. In vitro studies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression. [ABSTRACT FROM AUTHOR]

ConclusionsSampling surgical margins in trans-oral laser microsurgery for early glottic squamous cell carcinoma (SCC) may allow for increased local control rate, although with no difference in local control by endoscopic treatment alone.ObjectiveTo further delineate the role of routinely sampling separate surgical margins, in patients with early glottic SCC undergoing endoscopic laser resection.MethodsA retrospective case control study. One hundres and two early glottic cancer patients staged Tis-T2 underwent endoscopic laser surgery with curative intent as the primary treatment. Separate margins from the surgical bed were sampled following complete tumor resection in 64 patients; in 38 patients no margins were sampled.ResultsMargin sampling showed a tendency towards reduced risk for local recurrence, adjusted HR = 0.439 (p-value = 0.096). However, there was no difference in local control by endoscopic treatment alone. The patients with sampled margins were further divided based on margins’ status: 39 (61%) had negative margins, and 25 (39%) had positive margins. Compared with negative margins, patients with positive margins showed increased risk for recurrence, adjusted HR = 8.492 (p = 0.008). When margins were not sampled the risk for local recurrence was increased compared to negative margins (adjusted HR = 7.875,p-value = 0.008), and relatively comparable to what was observed when sampled margins were positive (adjusted HR = 0.927,p-value = 0.88). [ABSTRACT FROM PUBLISHER]

ConclusionThe Th17 cell frequency in peripheral blood and levels of IL-17 showed significant differences between patients with laryngeal squamous cell carcinoma and those with vocal cords polyps. Serum levels of IL-17 were correlated with laryngocarcinoma staging.ObjectivesTo investigate associations among the frequency of Th17 cells, levels of IL-17, and laryngeal squamous cell carcinoma.MethodEighty in-patients with laryngeal squamous cell carcinoma and 114 in-patients with polypus of the vocal cord were enrolled. Th17 cell frequencies in peripheral blood and serum levels of IL-17 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The tissue expression levels of IL-17 mRNA transcripts and protein were measured using quantitative RT-PCR or immunohistochemical detection, respectively.ResultsTh17 cell frequencies in peripheral blood and serum concentrations of IL-17 were significantly higher in patients with laryngocarcinoma compared with those in patients with polyps (p < 0.01 for both Th17 cells and IL-17 levels). Serum concentrations of IL-17 were significantly higher in patients with advanced laryngocarcinoma than in patients with early laryngocarcinoma (p < 0.01). The mRNA and protein levels of IL-17 were significantly higher in laryngocarcinoma tissues than in adjacent normal tissues (p < 0.01 for mRNA levels,p < 0.05 for protein levels). [ABSTRACT FROM PUBLISHER]

Conclusion The melanoma-associated antigens A1, -A9, -A11 (MAGE-A1, -A9, -A11) are relatively tumor-specific in laryngeal squamous cell carcinoma (LSCC), and could be ideal antigens for LSCC immunotherapy. In addition, MAGE-A9 probably is a poor prognostic marker for LSCC patients. Objective The MAGE-A family belongs to Cancer/testis antigens (CTA). However, the expression pattern of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC is still unclear. This study aims to evaluate the expression and possible prognostic role of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC patients. Methods The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC specimens was investigated by immunohistochemistry, and the association of their expression and the clinical parameters and the survival of LSCC patients were analyzed by chi-square test, Kaplan-Meier survival and Cox regression analysis. Results The expression rates of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC were 54.7%, 46.2%, and 51.9%, respectively. The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC was correlated with clinical stage, lymph node metastasis, and tumor size. The overall survival of LSCC patients with positive MAGE-A1, MAGE-A9, or MAGE-A11 expression was lower than the patients without MAGE-A1, MAGE-A9, or MAGE-A11 expression. Cox's multivariable analysis showed that MAGE-A9 expression was an independently poor prognostic factor for LSCC patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report the post-surgical and oncologic outcomes of patients who underwent supracricoid partial laryngectomy (SCPL). Methods: 90 patients who underwent SCPL between 1994 and 2014 were reviewed. 45 patients underwent cricohyoidopexy (CHP) and 45 patients cricohyoidoepiglottopexy (CHEP). Median nasogastric (NG) tube removal time, decannulation time, overall survival, disease-free survival and local control rates were calculated. The effect of the type of surgery on functional and oncologic outcomes were assessed. Results: Median NG tube removal time was 16.5 days (IQR = 10) and 14 days (IQR = 9) in CHP and CHEP patients, respectively (p > 0.05). Median decannulation time was 30 days (IQR = 26) and 19 days (IQR = 15) in CHP and CHEP patients, respectively (p < 0.05). Resection of one arytenoid significantly increased NG tube removal time. Median follow-up time was 55 months. There were 15 oncologic failures and the median time interval for tumor recurrence was 9 months. Five-year overall survival rate was 80.4%. The 3- and 5-year disease-free specific survival rates were 81.7 and 76.7%, respectively. Conclusions: Given the more extensive surgery applied for CHP, functional outcomes were better in patients with CHEP. Resection of an arytenoid had a negative outcome on swallowing. [ABSTRACT FROM AUTHOR]

Background: The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. Methods: The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. Results: In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site-specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. Conclusions: The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. [ABSTRACT FROM AUTHOR]

Study Objective: To assess whether the use of intraoperative opioids is associated with poor recurrence-free survival (RFS) and overall survival (OS) after lung cancer surgery.Design: Retrospective study.Setting: Academic hospital.Subjects: Patients with laryngeal primary or recurrent laryngeal squamous cell carcinoma who had surgery.Interventions: Intravenous opioids (remifentanil, fentanyl, sufentanil, and hydromorphone).Measurements: Univariate and multicovariate Cox proportional hazards models were applied to assess the effects of covariates of interest on OS and RFS.Main Results: A total of 195 patients were included. All received opioids intraoperatively. The multivariate analysis demonstrated that age (hazard ratio [HR], 1.03; P = .005), negative margin status (HR, 0.163; P = .001], postoperative chemotherapy (HR, 7.38; P < .001), and concurrent chemotherapy and radiation (HR, 3.11; P < .001) treatment and fentanyl equivalent use (HR, 1.001; P = .02) were all predictor factors for 3- and 5-year RFS. The same variables were predictor factors for OS (age: HR, 1.03 [P = .003]; negative margin status: HR, 0.14 [P = .001]; postoperative chemotherapy: HR, 4 [P < .0001]; and fentanyl equivalent use: HR, 1.001 [P = .02]).Conclusions: Our study demonstrates a very weak association between the use of intraoperative opioids and cancer recurrence after laryngeal squamous cell carcinoma surgery. [ABSTRACT FROM AUTHOR]

Objective:This study aimed to assess the influence of supra- and subglottic extensions and vocal fold mobility on outcome in a large monocentric cohort of 148 patients treated for tumour–node–metastasis stage T2N0 glottic carcinomas.Methods:In all, 107 glottic carcinoma patients had normal vocal fold mobility (T2aN0), and 41 had impaired vocal fold mobility (T2bN0). Treatment decisions were made by a multidisciplinary team.Results:Vocal fold mobility was associated with overall survival, disease-free survival, local control, larynx preservation and laryngectomy-free survival. For patients with T2a lesions, local control, laryngectomy-free survival and disease-free survival improved after surgery but overall survival did not. For patients with T2b lesions, local control, laryngectomy-free survival, disease-free survival and overall survival were all higher after surgery than after radiotherapy.Conclusion:This study highlights for the first time the importance of vocal fold mobility in treatment outcomes and is the first to assess its influence on survival. Updated tumour–node–metastasis classifications should consider the distinction between T2a and T2b lesions. [ABSTRACT FROM PUBLISHER]

Objective: This study aimed to investigate the expression of Notch1 in human laryngeal squamous cell carcinoma (LSCC) tissues and its relationship to clinicopathologic characteristics as well as their prognostic value in LSCC. Methods: Samples from 106 patients with LSCC were analyzed for Notch1 expression by immunohistochemical staining. The relationship between Notch1 expression and clinicopathologic parameters was subsequently analyzed. Univariate analysis and multivariate analysis of patient survival were examined using the Kaplan-Meier method and Cox proportional hazards model, respectively. Results: We found that Notch1 had positive expression in 71 of 106 cases of LSCC (66.98%), which was obviously higher than laryngeal normal tissues (P < .01) and significantly correlated with the clinical stage, lymph node metastasis, and histological grade (all Ps < .05). Univariate analysis revealed that Notch1 expression tended to show an unfavorable influence on overall survival (OS) and disease-free survival (DFS) (both Ps < .01). Multivariate analysis demonstrated that Notch1 was an independent prognostic factor for patients with LSCC (P < .05). Conclusion: These results reveal that Notch1 expression is a potential prognostic factor for malignant progression, metastasis, and survival of LSCC patients. Furthermore, it has been demonstrated that high expression of Notch1 was associated with unfavorable OS and DFS in LSCC patients. [ABSTRACT FROM AUTHOR]

Conclusions: Increased expression of Dicer may be a prognostic biomarker for patients with laryngeal squamous cell carcinoma (LSCC). Objectives: Recent studies have shown that many microRNAs (miRNAs) play an important role in the development and progression of human cancers. Dicer, one of the most important enzymes of the miRNA machinery, performs the final step of biogenesis of miRNAs. This study aimed to investigate the impact of Dicer expression on patient survival in human LSCC. Methods: We detected the expression of Dicer in larynx tissue specimens from 76 LSCC samples and 26 polyps by immunohistochemistry. The clinicopathological and prognostic significance of Dicer expression was investigated in LSCC. Results: Our data showed that the expression of Dicer was significantly higher in the LSCC than in the polyp tissue specimens. Moreover, the expression level of Dicer was significantly associated with the pTNM stage and tumor lymph node metastasis. Kaplan-Meier survival analyses revealed a strong association between tumor Dicer expression and the survival of the patients with LSCC. [ABSTRACT FROM AUTHOR]

Background Management of advanced laryngeal cancer is complex and ideal strategy is yet to be defined. This study evaluates the experience of a single head and neck oncologic centre in the management of T4 laryngeal cancer. Methods Retrospective assessment of cases primarily treated for T4a squamous cell carcinoma of the larynx, between 1980 and 2007, at a tertiary referral center. Results A total of 384 cases were studied. Five-year disease specific survival was 56.2% and local control 87.4%. Regional and distal control estimates were 90.3% and 88.3% respectively. Prognosis was significantly superior for cases treated with primary surgery compared to cases solely managed with non-surgical modalities. Positive surgical margins and regional disease worsened prognosis. Conclusion This study suggests that primary surgery remains a key element in the treatment of advanced laryngeal cancer. The need for well-designed, prospective, randomised studies in order to further evaluate the remaining role of primary surgery in the modern management of locally advanced laryngeal lesions is emphasized. [ABSTRACT FROM AUTHOR]

The aim of this study was an immunohistochemical assessment of the basement membrane antigen collagen IV (Col IV) in squamous cell carcinomas of the larynx and their respective nodal metastases. Forty radical laryngectomy specimens from 2009 to 2011 were randomly selected for this study. Tumor blocks were immunostained using the monoclonal antibody CIV 22 (Dako, Denmark). Col IV was evaluated using a semiquantitative morphometric method and graded according to its quantity and continuity. Col IV expression and epithelium-stroma interface (TESI) showed high significant differences between surface and deepness of larynx tumors. As for TESI, there was a strong relation between tumors with and without lymph node metastases. There was no correlation between desmoplasia and TESI disarrangement, but the latter had a high significant relation with histological grade. Col IV expression was independent of histological grading of the tumor. The results of the present study show an alterated distribution of collagen type IV with a significant loss in all cases of laryngeal cancer, reflecting tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Conclusions: Immunoglobulin (Ig) M is overexpressed in laryngeal squamous cell carcinoma (LSCC), and its expression has an independent protective impact on disease-free survival in LSCC. Objective: A number of studies have reported on the ectopic expression of Ig in cancer cells, yet there has been a lack of understanding of its clinical and prognostic significance. This study aimed to investigate the expression of IgM in resected specimens of LSCC and to evaluate its clinical significance and prognostic value. Methods: Immunohistochemistry (IHC) and Western blotting were used to detect the expression of IgM in LSCC and normal laryngeal tissues. The serum level of IgM was also analyzed by immunoturbidimetric assay. Results: IHC and Western blot studies demonstrated that IgM was overexpressed in LSCC specimens ( p < 0.001), while the serum level of IgM in patients with LSCC was not different from healthy controls. Chi-squared analysis revealed that the expression level of IgM was negatively correlated with regional lymph node metastasis and tumor stage ( p = 0.011 and 0.025, respectively). Univariate analysis showed that IgM expression was significantly correlated with enhanced disease-free survival (DFS) ( p = 0.004). In multivariate analysis, IgM retained its independent prognostic value for DFS ( p = 0.048, HR = 0.506, 95% CI = 0.257-0.995). [ABSTRACT FROM AUTHOR]

Conclusions: Nuclear nm23-H1 expression may be useful in identifying elderly patients operated for laryngeal squamous cell carcinoma (LSCC) at higher risk of recurrence. Further studies are needed to clarify the biological role of nm23-H1 in elderly patients with LSCC and to determine how to restore nm23-H1 loss of expression/function. Objectives: Nowadays more than 50% of cancer cases are elderly patients and this percentage is expected to be 70% by 2030. Despite advances in LSCC diagnosis and treatment, patient survival has not improved in the last two decades. Novel, effective strategies should rely also on receptor-mediated LSCC-targeted therapy. nm23-H1 protein is related to the tumor cells' metastatic potential, and low nm23-H1 expression in carcinomas often correlates with a poor prognosis. Methods: Immunohistochemistry and image analysis were used to investigate the prognostic value of nm23-H1 expression and subcellular localization in a series of 54 elderly patients consecutively undergoing primary surgery for LSCC. Results: On univariate analysis, the disease recurrence rate correlated inversely with nuclear nm23-H1 expression ( p = 0.014), and disease-free survival (DFS) was longer in patients whose nuclear nm23-H1 levels were ≥2.0% ( p = 0.022). On multivariate analysis, nuclear nm23-H1 expression (hazard ratio (HR) 2.77, p = 0.022) and N stage (HR 3.49, p = 0.007) were prognostically significant in terms of DFS. [ABSTRACT FROM AUTHOR]

Objective: Tumor-associated tissue eosinophilia (TATE) has been noted in human cancers, sometimes with different results regarding their association with clinical outcome. In this study, the association between TATE and prognostic parameters of supraglottic laryngeal cancer was analyzed. Materials and methods: Sixty-two patients with diagnosis of supraglottic laryngeal squamous cell carcinoma and who treated surgically in our center were evaluated. The cases were divided into 3 categories according to the average number of eosinophils per high-power field (400x): 0 (negative), 1-5 (grade 1+), more than 5 (grade 2+). Results: We found 24 TATE-negative (38.7%) and 38 TATE-positive (61.3%) cases. There was not any statistically significant correlation between TATE and tumor differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages, T stages (p>0.05). As expected, vascular invasion correlated with lymph node metastasis (p=0.001). Conclusion: The results of this study showed that TATE has no correlation with prognostic parameters such as histologic differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages and T stages in supraglottic laryngeal squamous cell carcinoma. The data suggest that stromal eosinophilic infiltration is not useful for determining biological aggressiveness in supraglottic laryngeal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. Materials and methods: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50–55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. Results: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. Conclusions: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker. [Copyright &y& Elsevier]

Objective:This study aimed to investigate the relationship between focal adhesion kinase expression and clinicopathological factors, cell apoptosis and proliferation, and overall survival, in laryngeal squamous cell carcinoma.Methods:Immunohistochemical staining was used to detect the expression of focal adhesion kinase and proliferating cell nuclear antigen in tissue samples. Apoptotic cells were assessed using the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (‘TUNEL’) method.Results:The proportion of focal adhesion kinase expression was 73.26 per cent in tumour tissues, significantly greater than in normal tissues (p < 0.05), and was significantly related to laryngeal cancer clinical stage, lymph node metastasis and overall survival (p < 0.05). In the tumour cases assessed, up-regulation of focal adhesion kinase expression was significantly associated with decreased cell apoptosis and increased proliferation (p < 0.05).Conclusion:These findings suggest that focal adhesion kinase may affect laryngeal squamous cell carcinoma progression through regulation of cell apoptosis and proliferation. Focal adhesion kinase expression is a major prognostic factor in laryngeal cancer patients. [ABSTRACT FROM PUBLISHER]

Angiogenesis is a hallmark of cancer, fundamental to its growth. The 'angiogenic switch' occurs when pro-angiogenic factors are not balanced by anti-angiogenic factors. A correlation between angiogenic properties and oncological prognosis (for laryngeal squamous cell carcinoma (LSCC) too) was first hypothesized in the 1990s. An exhaustive literature review was performed to investigate available data on angiogenesis markers and their biological role and therapeutic potential in LSCC. The prognostic significance of microvascular density in LSCC was investigated with endothelial targets, e.g. CD105, CD34, and CD31. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF receptor 2, angiogenin, hypoxia-inducible factor 1, and other biological markers were also studied. Only anti-EGFR therapy has been approved by the USFood and Drug Administration (FDA) for head and neck carcinoma in recent years, while several agents interfering with VEGF and its receptors are being studied. Experimental findings indicate that anti-CD105 monoclonal antibodies efficiently inhibit tumor angiogenesis. There are two main ways to approach the vascular profile of solid malignancies: by inhibiting new vessel formation (anti-angiogenic therapy) or selectively damaging neoplastic vessels (vascular targeting therapy). In advanced LSCC, both these strategies seem promising and warrant further preclinical and clinical investigation. [ABSTRACT FROM AUTHOR]