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Objective: To investigate epidemiological, clinical and oncological outcomes of patients with laryngeal verrucous carcinomas (LVC). Methods: Two independent authors investigated PubMed, Scopus and Cochrane Library for studies dedicated to epidemiological, clinical and oncological outcomes of patients with LVC. The following outcomes were investigated with PRISMA criteria: age; gender; tobacco/alcohol consumption; HPV infection; anatomical, pathological, therapeutic and survival outcomes. Studies were analyzed for bias through a validated clinical tool. Results: Of the 212 identified articles, 15 retrospective studies and one prospective uncontrolled study met our inclusion criteria. Three studies reported findings from national databases. The males/females ratio is 9/1. Mean age was 60.3 years, which was younger compared to other laryngeal malignancies. The alcohol, cigarette overuse and the HPV status of patients were lacking in most studies. Glottis and supraglottis were the most common anatomical locations, corresponding to 78.7% and 12.4% of cases, respectively. The main therapeutic approaches consisted of surgery, radiotherapy, surgery followed by radiotherapy. Treatments reported 5-year overall survival and disease-specific survival of 86.3 and 90.8, respectively. The 5- and 10-year local control rate were 83.6 and 72.6, respectively. The 10-year disease-specific survival was 80.2. Heterogeneity between studies was found for inclusion criteria, comorbidity data, and treatments. Conclusion: LVC is a rare laryngeal cancer associated with better survival and recurrence outcomes than laryngeal squamous cell carcinoma. The role of radiotherapy in the treatment regimen needs to be investigated in future prospective controlled studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Laryngeal squamous cell carcinoma is a prevalent cancer associated with poor prognosis in advanced stages. Despite advancements in diagnostic tools (e.g., narrow-band imaging), there have been minimal improvements in therapeutic approaches. The potential new frontier lies in the realm of biomarkers. This review aims to outline the current understanding of biomarkers in laryngeal cancer. Specifically, it concentrates on potential biomarkers, including heat shock proteins, metallothioneins, nuclear factor erythroid 2-related factor 2, micro ribonucleic acids, heme oxygenase, and cyclooxygenase-2. This review provides a survey of the existing literature on their role in laryngeal cancer. It also underscores the scarcity of the literature on this subject, highlighting the significant role of biomarkers in formulating more precise therapeutic strategies for individual patients. Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer among head and neck cancers. Despite a lower incidence of laryngeal carcinoma, new diagnostic techniques, and more targeted therapies, the overall survival has not changed significantly in the last decades, leading to a negative prognosis in advanced stages. Recently, several studies have focused on the identification of biomarkers that may play a critical role in the pathogenesis of LSCC. Reviewing the literature on the main databases, this study aims to investigate the role of some biomarkers in LSCC that are correlated with oxidative stress and inflammation: heat shock proteins; metallothioneins; nuclear factor erythroid 2-related factor 2; heme oxygenase; cyclooxygenase-2; and micro ribonucleic acids. This review shows that biomarker expression depends on the type, grade of differentiation, stage, and site of carcinoma. In addition, the role of these biomarkers in LSCC is still little-known and little-studied. However, the study of biomarker expression and the detection of a possible correlation with patients' epidemiological, clinicopathological, and therapeutics data may lead to better awareness and knowledge of the tumor, to the identification of the best therapeutic strategy, and the most proper follow-up protocol tailored for each patient. In conclusion, the achievement of these goals may improve the prognosis of LSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of human papillomavirus (HPV) in the survival of patients with head and neck squamous cell carcinoma (HNSCC) is an important topic. The recognition of additional markers could play a significant role in survival prognosis. Our study aimed to assess the roles of different molecular and immunohistochemical factors in the survival of patients with HNSCC. We analyzed 106 HNSCC samples and confirmed the roles of HPV DNA and p16, p53, and HPV16 E6 and E7 proteins in different subgroups of HNSCC. In addition to p16, the immunohistochemical overexpression of HPV16 E6 protein should be used for patient survival prognosis. The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC. [ABSTRACT FROM AUTHOR]

Background: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. Method: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). Results: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. Conclusion: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers. [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]

Objective: To evaluate the ultrasonography (US) characteristics of pharyngeal/laryngeal masses and the role of US in the assessment of laryngeal squamous cell carcinoma (LSCC).Methods: This study enrolled patients who underwent US for evaluation of pharyngeal/laryngeal masses between 2018 and 2021. Characteristics of pharyngeal/laryngeal masses and subsite invasion in cases of LSCC were evaluated using US.Results: Forty-six patients with pharyngeal (n = 22) /laryngeal (n = 24) masses were enrolled. The pathological results were benign and malignant in 7 (15.2%) and 39 (84.8%) patients, respectively. Malignant masses were significantly associated with US characteristics of heterogeneity (P = 0.002), irregular/speculated margin (P < 0.001), and increased internal vascularity (P = 0.014) compared with benign masses. In patients with LSCC, the detection rate of US for subsites invasion, including that of the anterior commissure, paraglottic space, outer cortex of the thyroid cartilage, cricoid cartilage, and extralaryngeal soft tissue, was similar to that of computed tomography (CT). Although the difference was not statistically significant, US more frequently demonstrated invasion of the inner cortex of the thyroid cartilage than CT (40.9% vs. 22.7%; P = 0.195). US and CT had a concordance rate of 81% (18 of 22 patients) in determining the tumour stage of the lesions.Conclusion: US could facilitate differentiation between benign and malignant masses of the pharynx and larynx in selective patients and has a possible role in the assessment of LSCC. [ABSTRACT FROM AUTHOR]

We present a new oral intake route in a hypopharyngeal cancer patient with severe complications. A 64-year-old man was diagnosed as having T2N0M0 squamous cell carcinoma of the posterior wall of the hypopharynx. He had previously undergone radiotherapy for laryngeal cancer and tricuspid valve replacement surgery, and also had atrial flutter and renal dysfunction. We performed surgery with curative intent. The hypopharynx was primarily closed after tumor resection. Laryngotracheal separation and tracheoesophageal diversion with end-to-end anastomosis of the trachea to the esophagus was performed. After surgery, complete oral feeding was achieved using the new pathway created. The larynx, contradictory to its typical role, can be used as a pathway to the esophagus using our revolutionary technique. [ABSTRACT FROM AUTHOR]

Objectives: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. Methods: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. Results: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). Conclusions: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF. [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]

Purpose: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study.Methods and Materials: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records.Results: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575).Conclusions: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar. [ABSTRACT FROM AUTHOR]

Combined small-cell carcinoma and squamous cell carcinoma of the larynx is an exquisitely rare and underreported primary tumor the head and neck region, with an English literature review revealing only 17 documented cases. There is limited information on how best to treat these patients oncologically, given the low number of reported cases. A subset of the reported cases also detail a unique local spread of this combined carcinoma, further obscuring the clinical picture of these patients. Here, we detail an 18th case, with nodal metastasis of only one component of the primary tumor, and discuss the published literature surrounding this etiology. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma (LSCC) is the main type of laryngeal cancer with poor prognosis. Incidence of LSCC increases every year, posing a great threat to human health. The underlying mechanism needs further study. Neutrophils are the most prevalent type of immune cells, which play vital roles in crosstalk between the microenvironment and cancer cells. In our study, we aim to figure out the complex regulation between neutrophils and LSCC. Our experiments showed that LSCC cells could promote the activation and mobility of neutrophils. And, in return, neutrophils enhanced the proliferation, migration, and invasion of LSCC. The subsequent results showed that IL-17 was highly expressed in neutrophil conditioned medium. Block of IL-17 could effectively inhibit the progression of LSCC induced by neutrophils. What is more, the results showed that IL-17 activated the JAK/STAT3 pathway in LSCC. Inhibition of the JAK/STAT3 pathway could significantly block neutrophil-induced LSCC progression. Our research reveals the complex interaction between neutrophils and LSCC cells, providing new ideas for the treatment of LSCC. [ABSTRACT FROM AUTHOR]

Treatment of squamous cell carcinoma of the supraglottic larynx (SCCSL) in Denmark has changed in several ways from the year 2000 to 2014, including the introduction of IMRT radiation technique and the addition of concurrent chemotherapy (CRT), as well as systematic reduction in waiting times until treatment initiation. Our aim is to investigate the effect of the abovementioned factors on overall survival (OS) and locoregional control (LC) for SCCSL patients. Retrospective cohort study with data from the DAHANCA database. We used the Kaplan–Meier and Cumulative Incidence plots as well as Cox regression analysis. We found a statistically significant improvement of the 5-year OS of 19.3 percentage points (pp). Cox regression found LC was not improved in patients receiving CRT compared to radiotherapy (RT) alone. Introduction of CRT treatment for head and neck cancers in general is known to improve LC. We could not demonstrate this effect for SCCSL specifically, as our results were not statistically significant on this point. OS was significantly improved. [ABSTRACT FROM AUTHOR]

Aim: We aimed to show the immunohistochemical expression of programmed death ligand 1 (PD-L1) in laryngeal squamous cell carcinomas (SCCs). Materials and methods: The study includes 52 laryngeal SCC cases that underwent surgical resection. Immunohistochemical staining of PD-L1 (Clone 22C3) was applied to the sections obtained from paraffin blocks. Combined Positive Score (CPS) was evaluated as described in manuals. Tumor Proportion Score (TPS) was assessed by the percentage of positive tumor cells which were designated as positive if ⩾1% of the tumor cells showed membranous staining. Results: There were 35 cases (67.3%) having CPS < 1 and 17 cases (32.7%) having CPS ⩾ 1. There was no relationship between CPS, TPS, and the clinicopathological data. Conclusion: Further studies with a large number of advanced-stage cases are needed. [ABSTRACT FROM AUTHOR]

Glottic squamous cell carcinoma (SCC) in stages I or II can be treated by transoral CO2 laser microsurgery (TLM) or exclusive radiotherapy (RT). To compare the oncological results of patients treated with TLM, to those treated with RT, in a tertiary hospital. Data from patients diagnosed with glottic SCC in stages I and II between 2004 and 2018 were analyzed. Response to treatment was studied in terms of recurrence, local control and laryngeal preservation. Of 164 patients, 63.41% received treatment with TLM and 36.58% with RT. 26.21% presented a recurrence or progression of the tumor. Both treatments obtained good local control rates (84.15% in the case of TLM and 89.6% in the case of RT) and no significant association was found between tumor recurrence and type of treatment, nor with the involvement of the anterior commissure. However, treatment with RT obtained worse laryngeal preservation rate compared to TLM (81.6% and 100% respectively) (p <.001LR). Conclusions and significance: Both treatments obtained good oncological results. There were no significant differences regarding local control. However, TLM obtained a better laryngeal preservation rate. The involvement of the anterior commissure was not a poor prognosis factor for tumor recurrence. [ABSTRACT FROM AUTHOR]

Background: Incidence of thyroid gland invasion in advanced laryngeal cancers is low. Ipsilateral or total thyroidectomy along with total laryngectomy has been controversial and there has been no consensus over the management of thyroid gland in advanced laryngeal cancers. Objective: To determine the frequency of thyroid gland invasion in locally advanced laryngeal squamous cell carcinoma and the risk factors associated with it. Material and methods: A retrospective review of patients with laryngeal squamous cell carcinoma operated at our center between January 2011 and December 2018 was carried out. Patients undergoing upfront or salvage laryngectomy with or without neck dissection along with hemi or total thyroidectomy were included. Histopathology reports were reviewed to record the involvement of thyroid gland. Results: Invasion of thyroid gland by squamous cell carcinoma larynx was seen in 10 (10.9%) patients out of 92. All of the cases showed direct extension of the tumor. Trans-glottic, subglottic, and tumors with extra laryngeal spread were found to be significantly associated with thyroid gland invasion. Patients with thyroid gland invasion showed higher rate recurrence. Conclusion and significance: Incidence of thyroid gland invasion in squamous cell carcinoma larynx is low, allowing us not to address thyroid routinely in patients undergoing total laryngectomy for laryngeal carcinoma. [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]

Purpose: The early results of a phase 1 study of stereotactic ablative radiation therapy for early-stage glottis cancer were previously reported. However, additional late adverse events occurred in the second arm during the follow-up period. In this study, the dose-limiting toxicities and premature closure of the clinical trial are reported.Methods and Materials: Thirteen patients with cT1-2N0M0 squamous cell carcinoma of the glottis were enrolled between May 2015 and July 2018. Seven patients in the first arm received 59.5 Gy to the gross tumor volume and 47.6 Gy to the remaining larynx, delivered in 17 fractions. The second arm dose was 55 Gy and 40.7 Gy in 11 fractions to the gross tumor volume and the remaining larynx, respectively. Patients were treated according to the simultaneous integrated boost approach with volumetric modulated arc therapy.Results: The median follow-up was 37 months (range, 6-41.4) for the first arm and 14.5 months (range, 4.8-21.5) for the second arm. Maximum acute toxicity was grade 2 laryngeal mucositis for each arm. Maximum chronic toxicity was grade 3 laryngeal inflammation, occurring in 2 patients (33.3%) in the second arm. One patient underwent a laryngomicrosurgical biopsy for a vocal cord ulcer, and another patient underwent supraglottic laryngectomy because of arytenoid cartilage necrosis. In the first arm, chronic toxicity was not observed, except for grade 1 laryngeal edema in 1 patient.Conclusions: The phase 1 dose escalation study was terminated early because of the unexpected dose-limiting toxicities occurring in patients in the second arm. It was concluded that stereotactic ablative radiation therapy is not feasible for early-stage glottic cancer owing to treatment-related toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Early-stage glottic larynx squamous cell carcinoma (GLC) is a relatively common disease with excellent oncologic control, but treatment is associated with acute dysphagia and long-term voice quality changes. This phase 1 study of hypofractionated radiation therapy for early-stage GLC increased the fraction size while reducing the number of fractions until 5-fraction stereotactic ablative radiation therapy (SABR) was delivered.Methods and Materials: Eligible patients had received a diagnosis of stage Tis to T2 GLC. Patients who had undergone prior curative-intent surgery were excluded. The equipotent dose levels were as follows: (1) level 0, 50 Gy in 15 fractions (n = 4); (2) level 1, 45 Gy in 10 fractions (n = 13); and (3) level 2, 42.5 Gy in 5 fractions (SABR level, n = 12). Grade 3 or 4 laryngeal edema, voice, dyspnea, stridor, or cough were the predefined dose-limiting toxicities.Results: Twenty-nine patients were enrolled from November 2013 to March 2017. The median and minimum follow-up times were 39.2 and 13 months, respectively. Two actively smoking patients, 1 treated in level 1 (grade 4 laryngeal edema, grade 3 dysphagia) and 1 treated in level 2 (grade 3 laryngeal necrosis, dysphagia), developed dose-limiting toxicities. The former patient soon developed a local recurrence, and the latter patient recovered. There were a total of 5 local recurrences: 2 in level 0 and 3 in level 1. The Voice Handicap Index results showed robust long-term voice quality with median values of 7 and 0 at 6 and 12 months, respectively.Conclusions: Given the tolerability, excellent voice outcomes, and preliminary efficacy data of 5-fraction glottic larynx SABR, this regimen warrants further study. [ABSTRACT FROM AUTHOR]

Objectives: Laryngeal squamous cell carcinoma (LSCC) can involve different anatomic subunits with peculiar surgical and prognostic implications. Despite conflicting outcomes for the same stage of disease, the current staging system considers different lesions in a single cluster. The aim of this study was to critically discuss clinical and pathologic staging of primary and recurrent advanced LSCC in order to define current staging pitfalls that impede a precise and tailored treatment strategy. Methods: Thirty patients who underwent total laryngectomy in the past 3 years for primary and recurrent advanced squamous cell LSCC were analyzed, comparing endoscopic, imaging, and pathologic findings. Involvement of the different laryngeal subunits, vocal-fold motility, and spreading pattern of the tumor were blindly analyzed. The diagnostic accuracy and differences between clinicoradiologic and pathologic findings were studied with standard statistical analysis. Results: Discordant staging was performed in 10% of patients, and thyroid and arytenoid cartilage were the major diagnostic pitfalls. Microscopic arytenoid involvement was significantly more present in case of vocal-fold fixation (P = .028). Upstaging was influenced by paraglottic and pre-epiglottic space cancer involvement, posterior commissure, subglottic region, arytenoid cartilage, and penetration of thyroid cartilage; on the contrary, involvement of the inner cortex or extralaryngeal spread tended to be down-staged. Radiation-failed tumors less frequently involved the posterior third of the paraglottic space (P = .022) and showed a significantly worse pattern of invasion (P < .001). Conclusions: Even with the most recent technologies, 1 in 10 patients with advanced LSCC in this case series was differently staged on clinical examination, with cartilage involvement representing the main diagnostic pitfall. [ABSTRACT FROM AUTHOR]

Introduction: The concept of neck dissection (ND) in the management armamentarium of head and neck squamous cell carcinoma has evolved throughout the years. Nowadays, ND becomes more functional.Methodology: A retrospective study of 865 patients was performed at Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital to investigate the feasibility of selective ND (SND). All patients with squamous cell carcinoma of the pharynx and larynx who received primary radiation and underwent salvage ND were included in the study.Result: A total of 29 NDs were analyzed. In 17 neck sides, viable metastases were found (58%), whereas in the other 12 specimens there were no viable metastases. In 16 of the 17 necks (94%), the metastases were located either in level II, III, or IV or in a combination of these 3 levels. Level V was involved in only 1 case (6%).Conclusion: It is well justified to perform a salvage SND (levels II, III, and IV) for pharyngeal and laryngeal carcinoma after primary radiation. In carefully selected cases of supraglottic and oropharyngeal carcinoma, a superselective ND also appears as an efficient option. [ABSTRACT FROM AUTHOR]

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]

Objectives:This study aimed to: describe the incidence of thyroid gland involvement in advanced laryngeal cancer, analyse patterns of spread to the thyroid and elucidate predictors of thyroid involvement.Methods:A retrospective review was performed on patients who underwent laryngectomy from 1991 to 2015 as a primary or salvage treatment for squamous cell carcinoma of the larynx, hypopharynx or base of tongue. The incidence of thyroidectomy during total laryngectomy, type of thyroidectomy, incidence of gland involvement, route of spread, and positive predictors of spread were analysed and reported.Results:A total of 188 patients fit the inclusion criteria. Of these, 125 (66 per cent) underwent thyroidectomy. The thyroid was involved in 10 of the 125 patients (8 per cent), 9 by direct extension and 1 by metastasis. Cartilage invasion was a predictor of thyroid gland involvement, with a positive predictive value of 26 per cent.Conclusion:There is a low incidence of thyroid gland involvement in laryngeal carcinoma. Most cases of gland involvement occurred by direct extension. Thyroidectomy during laryngectomy should be considered for advanced stage tumours with cartilage invasion. [ABSTRACT FROM PUBLISHER]

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]

Objectives: This study aimed to evaluate serum cytokine concentrations in healthy individuals and laryngeal squamous cell carcinoma patients. Methods: A total of 59 laryngeal squamous cell carcinoma patients and 44 healthy controls were included. Multiplex analysis of interleukins 2, 4, 5, 6, 10, 12, 13 and 17 and interferon-gamma with respect to the presence of laryngeal carcinoma, tumour-node-metastasis T stage, nodal involvement and larynx subsite was performed. Results: Statistical analysis revealed no difference in serum cytokine levels between patients and healthy controls. The serum interleukin-12 concentration was significantly higher in patients with early (T1-2) than in those with late (T3-4) stage disease and without nodal involvement (p < 0.05). Serum interleukin-10 levels were significantly higher in T3-4 stage than in T1-2 stage patients (p < 0.05). Additionally, serum interleukin 10, 12 and 13 concentrations (p < 0.05) and interleukin-6 concentration (p < 0.01) were significantly higher in patients with T1-2 stage supraglottic vs glottic tumours. Conclusion: Serum cytokines level cannot be used as laryngeal squamous cell carcinoma markers. Progression from T1-2 to T3-4 stage is followed by decreased serum interleukin-12 levels and increased interleukin-10 levels. Nodal involvement is associated with lower serum interleukin-12 levels. In patients with early stage tumours, serum interleukin 6, 10, 12 and 13 concentrations are significantly higher in those with supraglottic vs glottic tumours. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors.Methods and Materials: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy.Results: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT.Conclusions: According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted. [ABSTRACT FROM AUTHOR]

Background:The optimal management of glottic carcinoma involving the anterior commissure is controversial.Method:A retrospective analysis was conducted of 76 patients with glottic squamous cell carcinoma treated by transoral carbon dioxide laser resection by a single surgeon.Results:Sixty-three patients (with tumour stage Tis–T3) were eligible for inclusion. Thirty patients had involvement of the anterior commissure; these patients were significantly more likely to have either uncertain or positive margins (63.3 vs 30.3 per cent, p = 0.012), and were also more likely to receive adjuvant radiotherapy (40 vs 3.2 per cent, p = 0.0005). The overall laryngeal preservation rate was 96.8 per cent; there was no statistically significant difference between those with and without anterior commissure involvement (96.7 and 96.9 per cent respectively).Conclusion:Transoral laser resection with the use of adjuvant radiotherapy in a minority of patients with adverse pathological findings can be recommended for the primary treatment of anterior commissure glottic cancer from an oncological perspective; excellent local control and laryngeal preservation rates can be achieved. [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: Assessment of thyroid cartilage invasion (tumor extension through inner cortex) and thyroid cartilage penetration (tumor involving both the inner and outer cortices of thyroid cartilage) may be challenging with CT (Computed Tomography) and MR imaging (Magnetic Resonance Imaging). Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that provides both anatomic and metabolic information. Quantitative data obtained from PET/CT, also known as PET/CT parameters, include maximum, mean or peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM) and normalized standardized added metabolic activity (NSAM). Our aim was to examine if FDG PET/CT parameters could differentiate thyroid cartilage invasion from penetration.Methods: 50 patients who underwent PET/CT before laryngectomy for squamous cell carcinoma of the larynx, had SUVmax, SUVmean, SUVpeak, TLG, MTV, SAM and NSAM calculated on a dedicated workstation. Univariate and multivariate analysis was performed. ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven thyroid cartilage invasion or penetration.Results: Of the 50 patients, 50% (25/50 patients) had history of prior radiation therapy. Among the previously irradiated group, 24% had thyroid cartilage invasion and penetration. 8% of the patients in this group had thyroid cartilage invasion only. Among the non-irradiated group, 76% had thyroid cartilage invasion and penetration, 8% had thyroid cartilage invasion without penetration. ROC analysis revealed that none of the PET/CT parameters had enough power to predict thyroid cartilage penetration, but TLG, MTV and SAM had enough power to predict thyroid cartilage invasion in non-irradiated patients. TLG, MTV, SAM and NSAM had enough power to predict thyroid cartilage invasion and penetration in irradiated group.Conclusion: TLG, MTV and SAM have enough power to predict thyroid cartilage invasion and penetration in irradiated patients. PET/CT parameters do not have enough potential to differentiate thyroid cartilage invasion from penetration. [ABSTRACT FROM AUTHOR]

In the article we present the case of 42 years old woman with diagnosed squamous cell carcinoma of larynx and inferior pharynx. In 2013 the patient underwent primary concurrent chemoradiotheraphy (CCRT). Due to the recurrence (2015) total laryngectomy (TL) was performed – the operation proved non-radical. The report contains a summary of the relevant literature concerning the available diagnostic methods and surgical and non-surgical managment of advanced laryngeal cancer. [ABSTRACT FROM AUTHOR]

Primary laryngeal non-Hodgkin's lymphomas are very rare constituting 1% of all laryngeal tumors. Of these, the peripheral T-cell lymphomas are extremely rare with <10 case reports in English literature. Laryngeal lymphomas are clinically confused with the more common laryngeal malignancies like squamous cell carcinoma, thus, histopathological examination is mandatory for diagnosing, sub-typing and guiding therapy for these lymphomas. We report a case of rare primary laryngeal peripheral T-cell lymphoma with autopsy findings. [ABSTRACT FROM AUTHOR]

Conclusion: The degree of midline crossing of lateral supraglottic cancer does not significantly change its rate of contralateral cervical metastasis. The rate of occult metastasis is too high to take the risk of contralateral regional recurrence. We support routine bilateral neck dissection even in lateral supraglottic cancers with no or minimal midline crossing. Objectives: Data on the rate of contralateral cervical metastasis of laterally located supraglottic cancer, the effect of its degree of midline crossing on contralateral cervical metastasis, and its treatment are still controversial. Methods: This was a retrospective cohort, chart review involving 305 surgically treated patients with T1-3 squamous cell carcinoma of the supraglottic larynx. In all, 184 patients had bilateral neck dissection; 86 N0 contralateral necks were followed up. Thirty-five patients who needed postoperative radiation therapy because of the primary tumor or ipsilateral neck dissection specimen also received radiation therapy to the contralateral neck. The degree of midline crossing at the epiglottis was measured on a laryngectomy specimen with a ruler and expressed as 'no,' '<5 mm' or '≥5 mm.' Results: The rates of occult and overall contralateral metastasis in our series were 16% and 28%, respectively. There was no statistically significant difference between contralateral neck metastasis and recurrence rates in the neck dissection, follow-up, and irradiation groups according to the degree of midline crossing. [ABSTRACT FROM AUTHOR]

Introduction: A rare case of basaloid squamous cell carcinoma (BSCC) of the larynx, which has not been previously reported, is described. Case Report: A 60-year-old man was presented to the Otolaryngology Department with progressive dyspnoea and dysphagia to solids for over a period of 1 week. Direct laryngoscopy revealed a tumour at the laryngeal aspect of the epiglottis, which prolapsed into the laryngeal inlet each time the patient inspired. This resulted in an inspiratory stridor despite adequate glottic opening and normal mobility of the vocal cords. Conclusion: Therefore, in cases where a ball-valve lesion causes intermittent life-threatening airway obstruction, BSCC of the larynx, though rare, must be considered as a differential diagnosis. [ABSTRACT FROM AUTHOR]

With the growing acceptance of nonsurgical therapies for laryngeal squamous cell carcinomas (LSCCs), it has become important to delineate surgical salvage strategies for disease recurrences. Total laryngectomy is often recommended, but appropriately selected laryngeal recurrences may be treated successfully with partial laryngeal surgery: laryngeal function can be preserved with oncological efficacy. The main available studies dealing with partial laryngeal surgery in recurrent carcinoma were critically reviewed. The most appealing feature of salvage transoral laser surgery (TLS) is the opportunity to make tumor-tailored excisions without any reconstructive limitations and retaining the option to switch to open partial laryngectomy. A recent detailed review of 11 series found a pooled local control rate of 57% after a first TLS procedure. Supracricoid laryngectomy (SCL) seems to achieve good local control rates in selected cases of recurrent supraglottic-glottic carcinoma: one review considering seven series calculated that 85% of the patients treated with salvage SCL after radiotherapy experienced no local recurrence; and total laryngectomy after failure of salvage SCL afforded an overall local control rate of 65%. Neck dissection is mandatory in all cases of local LSCC recurrence with evidence of neck metastases, and routine elective neck dissection is recommended for recurrent supraglottic and transglottic cancers. [ABSTRACT FROM AUTHOR]

The article focuses on the use of orthotopic mouse model to analyze the laryngeal squamous cell carcinoma. It mentions that the animals were monitored through direct laryngoscopy and ultrasound for the survival and growth of tumor. It offers information on the phenotype and malignant behavior that creates its natural biologic behavior as of laryngeal cancer patients.

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]

Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments. Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs. Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice. [ABSTRACT FROM AUTHOR]

Objectives. Metastasis of laryngeal squamous cell carcinoma (SCC) to the intra-abdominal gastrointestinal tract is exceedingly rare. The objectives of this case report are to describe a case involving a perforated metastasis of a laryngeal SCC to the ileum and to review the literature pertaining to other similar cases. Methods. A review of patient’s chart and a review of the English literature involving malignant SCC of the larynx with metastasis to the small bowel. Results. We describe the case of a 58-year-old man who had failed induction chemotherapy and underwent a laryngopharyngectomy with bilateral neck dissection and pectoralis major flap for a T4N2c laryngeal SCC. Subsequently, the patient was treated with postoperative radiation and cituximab. The patient went on to present with symptoms consistent with a ruptured appendix, supported by ultrasound imaging. The patient was taken to the operating room where a right hemicolectomy was performed. Pathological gross examination confirmed a 4 cm transmural perforation in the terminal ileum. Microscopy demonstrated deposits of metastatic squamous cell carcinoma in the surrounding smooth muscle. Metastatic carcinoma was also found in a separate nodule from the abdominal wall. The patient had an uncomplicated post-operative period, and survived several months thereafter. Conclusions. Metastasis of laryngeal SCC to the small bowel with perforation is exceedingly rare, but possible. These patients may be successfully managed with resection. [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]

Over 2,200 cases of carcinoma of the larynx are diagnosed in the UK annually, with an overall 5-year survival rate of 67%. Angiogenesis is vital for the growth and metastasis of solid tumours and the expression of key angiogenesis-related proteins has been shown to be of prognostic significance. In this study we reported the expression of key angiogenesis-related factors, selected from a pilot array study, in a cohort of laryngeal tumours and associated meta-static lymph nodes. Forty patients diagnosed with squamous cell carcinoma of the larynx were recruited. Tissue specimens were obtained intra-operatively, prior to chemo- and/or radiotherapy, from the tumours and secondary lymph nodes. The patient group comprised 32 men and 8 women with a mean age of 68 years (range, 51-89 years). The relative expression of the angiogenesis-related proteins angiogenin, interleukin (IL)-8, tissue inhibitor of metalloproteinases-1 (TIMP-1), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-basic and insulin-like growth factor binding protein 3 (IGFBP3) was determined in the tissue lysates by ELISA. The expression of angiogenin was higher in early-stage compared with late-stage tumours (P=0.034) and the expression of IGFBP3 was higher in tumours compared with the metastatic lymph nodes (P=0.016). No statistically significant differences were recorded for VEGF, FGF, TIMP-1 or IL-8 between tumour stages or primary tumours and lymph nodes. To the best of our knowledge, this study was the first to investigate multiple angiogenic factors in the lysates of laryngeal carcinomas and metastatic nodes and identified angiogenin and IGFBP3 as factors possibly involved in tumour progression. A greater understanding of their function may offer novel prognostic and/or therapeutic options. [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]

J Oral Pathol Med (2013) 42: 154-161 Background: BCL2L12 is a recently identified gene belonging to the BCL2 family, members of which are implicated in head and neck squamous cell carcinoma (HNSCC). We have recently shown that BCL2L12 mRNA expression is an unfavorable prognostic indicator in nasopharyngeal carcinoma (NPC) and that BCL2L12 can be regarded as a novel, useful tissue biomarker for the prediction of NPC patients' short-term relapse. The aim of this study was to analyze the mRNA expression of the novel apoptosis-related gene BCL2L12 in patients with HNSCC. Methods: Total RNA was isolated from 53 malignant tumors originating in larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissue specimens, resected from patients with HNSCC. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification in head and neck tissues was developed using the SYBR® Green chemistry. After preparing cDNA by reverse transcription, relative quantification was performed using the comparative CT () method. Results: BCL2L12 mRNA levels were lower in laryngeal tumors of advanced tumor, node, metastasis (TNM) stage or bigger size and in well-differentiated malignant tongue neoplasms, compared with early-stage laryngeal tumors or poorly differentiated tongue tumors. Interestingly, the BCL2L12 expression showed significant discriminatory value, distinguishing efficiently patients with tongue squamous cell carcinoma (SCC) from non-cancerous population. Conclusions: This is the first study examining the BCL2L12 mRNA expression in HNSCC. Our results suggest that BCL2L12 mRNA expression may serve as a potential prognostic biomarker in tongue and/or larynx SCC, which principally constitute the great majority of HNSCC cases worldwide. [ABSTRACT FROM AUTHOR]

Objective:We present the first reported case of a paraganglioma of the larynx occurring concurrently with squamous cell carcinoma in an irradiated neck.Method:We present a case report and a literature review of paraganglioma of the larynx.Case report:A 78-year-old woman was found to have a mass on the laryngeal surface of the epiglottis and non-functioning larynx, four months after radical radiotherapy for biopsy-proven squamous cell carcinoma. Repeated positron emission tomography computed tomography was highly suggestive of residual malignancy. Given these findings, and the fact that the patient was aspirating, she was treated with total laryngectomy, and was found to have a paraganglioma of the larynx.Conclusion:This is the first report of such a case. Its importance is three-fold in that it demonstrates: the coexistence of paraganglioma and squamous cell carcinoma; the difficulties that can be encountered in the diagnosis; and the use of radiotherapy in the treatment of paraganglioma. [ABSTRACT FROM PUBLISHER]

Background:Spontaneous regression of solid malignancy is extremely rare. It is virtually unheard of in the last half century in the published literature. The overwhelming majority of medical professionals do not know that this phenomenon exists.Case report:This paper reports such a case involving a patient with proven laryngeal squamous cell carcinoma in New Zealand. Whilst waiting for definitive treatment, he was afflicted with prolonged septicaemia secondary to peritonitis from percutaneous endoscopic gastrostomy tube insertion. Following a total laryngectomy, histology of the specimen did not contain any evidence of neoplasia.Conclusion:Based predominantly on work established by Dr William Coley, we believe that a period of prolonged pyrexia preceding definitive surgery contributed to this apparent ‘miracle’. The time may be ripe to further debate on whether the medical profession should consider pyrexia therapy as a last resort treatment for patients deemed incurable by conventional methods. [ABSTRACT FROM PUBLISHER]

Objective: PTEN (phosphatase and tensin homologue deleted on chromosome 10), also referred to as MMAC1 (mutated in multiple advanced cancers) gene was recently identified as a putative tumor suppressor in a variety of malignant tumors. PTEN expression has been investigated in some squamous cell carcinomas (SCC) of head and neck. However, there is only little knowledge about laryngeal malignancies. Therefore, we examined PTEN product protein immunohistochemically in 30 consecutive laryngeal specimens from patients with laryngeal SCC and compared the results according to the clinicopathologic characteristics of the patients.Method: Surgical resection specimens of patients with laryngeal SCC were stained for PTEN protein using a primary rabbit polyclonal anti-PTEN antibody. Standard avidin-biotin immunohistochemical analysis was used to process the sections. The extent and intensity of PTEN staining in the specimens were compared according to the age and sex of the patients and localization, differentiation, size and stage of the tumor.Results: Out of 30 tumoral specimens (23 glottic and 7 supraglottic) 22 showed decreased PTEN staining intensity compared to the adjacent normal tissue. The extent of cytoplasmic PTEN staining was significantly less in supraglottic tumors (p < 0.05). When characteristics of the patients were analyzed according to the extent of cytoplasmic PTEN staining no difference was observed according to age, sex, measure, differentiation, T or N status.Conclusion: A significant decrease in the extent of PTEN staining was observed in supraglottic SCC. It could be worthwhile to test if PTEN expression is diminished in patients with more aggressive laryngeal tumors, with special attention to tumor localization in larger series. [ABSTRACT FROM AUTHOR]

Objectives: The study was intended to compare the outcomes for T1-T2N0M0 glottic squamous cell carcinoma with anterior commissure involvement who had undergone partial laryngectomy (PL) or radiotherapy (RT).Materials and Methods: We retrospectively analyzed 256 patients who were treated by RT (n = 70) or PL (n = 186). Patients received prophylactic irradiation of the neck in RT group whereas PL was not associated with lymphadenectomy. Propensity score matching (PSM) was used to eliminate the baseline variations.Results: The average age of the RT group (67 years) was significantly higher than that of the PL (59 years). Local recurrence was noted in 14 patients of the RT group and 22 of the PL. While regional recurrence was noted in only 1 patient of the RT group and 23 of the PL. After PSM, the 5-year overall survival (82.8% vs. 83.9%, p = 0.302), 5-year cancer-specific survival (88.3% vs. 89.7%, p = 0.793), 5-year local relapse-free survival (79.3% vs. 84.5%, p = 0.127) were not significantly different between two groups. However, 5-year regional relapse-free survival in the RT group was significantly better than that in the PL (100% vs. 87.1%, p = 0.014). In the PL group, infection, granuloma, laryngeal stenosis, chylous leakage, and pharyngeal fistula were reported in six, 11, 12, one, and two patients, respectively.Conclusions: RT resulted in comparable rates of survival, local control, and larynx preservation compared to PL. However, RT was associated with higher regional control rate. The complication rates were extremely low in RT group. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of the immune response to cancer is of increasing importance, with a determining role in the response to the treatments and prognosis of patients. In this work, we studied whether the immune response (local and systemic) can influence the treatment response and prognosis of patients with laryngeal and hypopharyngeal carcinoma receiving induction chemotherapy (ICT). We observed that the relationship between neutrophils and lymphocytes (NLR) in peripheral blood and PD-L1 expression in the tumor is related to ICT response and patient prognosis. The identification of new biomarkers related to the immune response may allow a better selection of treatments and the identification of potential therapeutic targets. Our goal was to assess the correlation of immune parameters with the response to induction chemotherapy (ICT) in head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment biopsies from 64 patients with HNSCC that received ICT were assessed for PD-L1 protein expression and density of CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). In addition, the neutrophil-to-lymphocyte ratio (NLR) was calculated from pretreatment whole blood counts. In total, 55% of cases exhibited PD-L1 combined proportion score (CPS) positivity (≥1% stained cells). PD-L1 CPS positivity correlated with a high density of both CD8+ (p = 0.01) and FOXP3+ (p < 0.001) TILs. There was no correlation between PD-L1 expression or TIL density and NLR values. In univariate analyses, the absence of PD-L1 CPS expression (p = 0.042) and a high NLR (p = 0.034) were significantly correlated with response to ICT. Neither CD8+ TIL (p = 0.99) nor FOXP3+ TIL densities (p = 0.71) were associated with response to ICT. In multivariate analysis, only a high NLR was associated with response to ICT (HR = 4.06, 95% CI = 1.06–15.5, p = 0.04). In addition, a high NLR was also independently associated with lower disease-specific (p = 0.03) and overall survival rates (p = 0.04), particularly in the subset of patients who received definitive surgical treatment. These results suggest that NLR could emerge as a predictive biomarker of response to ICT. [ABSTRACT FROM AUTHOR]

Simple Summary: Organ preservation protocols have become first line therapy for the majority of advanced laryngeal cancers. Unfortunately, up to one third of patients will develop recurrent disease requiring salvage surgery. These tumors tend to display aggressive features when compared to primary disease. The aim of this study is to identify genomic alterations associated with poor prognosis in the recurrent setting to guide precision therapy and identify potential targetable pathways. Here we show that mutations in the oxidation pathway, specifically the KEAP1-NFR2 pathway, predict survival in a cohort of patients undergoing salvage laryngectomy. Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1–9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort. [ABSTRACT FROM AUTHOR]