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Background: Narrow-band imaging is an advanced endoscopic technology used to detect changes on the laryngeal tissue surface, employing a comparative approach alongside white-light endoscopy to facilitate histopathological examination. Objective: This study aimed to assess the utility and advantages of NBI (narrow-band imaging) in identifying malignant laryngeal lesions through a comparative analysis with histopathological examination. Methods: We conducted a systematic literature review, utilizing databases such as PubMed, the CNKI database, and Embase for our research. Results: We analyzed the articles by reviewing their titles and abstracts, selecting those we considered relevant based on determined criteria; in the final phase, we examined the relevant studies according to the specific eligibility criteria. Conclusions: Narrow-band imaging is an advanced endoscopic technology that demonstrates its efficacy as a tool for diagnosing malignant laryngeal lesions and comparing them to premalignant lesions. The European Society of Laryngology has implemented a standardized classification system for laryngeal lesions to enhance data correlation and organization. [ABSTRACT FROM AUTHOR]

Background: Narrow-band imaging is an advanced endoscopic technology used to detect changes on the laryngeal tissue surface, employing a comparative approach alongside white-light endoscopy to facilitate histopathological examination. Objective: This study aimed to assess the utility and advantages of NBI (narrow-band imaging) in identifying malignant laryngeal lesions through a comparative analysis with histopathological examination. Methods: We conducted a systematic literature review, utilizing databases such as PubMed, the CNKI database, and Embase for our research. Results: We analyzed the articles by reviewing their titles and abstracts, selecting those we considered relevant based on determined criteria; in the final phase, we examined the relevant studies according to the specific eligibility criteria. Conclusions: Narrow-band imaging is an advanced endoscopic technology that demonstrates its efficacy as a tool for diagnosing malignant laryngeal lesions and comparing them to premalignant lesions. The European Society of Laryngology has implemented a standardized classification system for laryngeal lesions to enhance data correlation and organization.

Background: Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. Materials and methods: In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. Results: The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801). Conclusion: Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC. [ABSTRACT FROM AUTHOR]

Objective:Complete en bloc supraglottic tumor excision with transoral laser microsurgery (TLM) can be achieved with good postoperative outcomes. We report surgical feasibility and the postsurgical outcomes of en bloc resection of supraglottic laryngeal squamous cell carcinomas (LSCC) with TLM.Methods:Seventeen patients who underwent TLM for supraglottic laryngeal cancer were included in the study. Demographic and pathological data, clinic and follow-up outcomes of the patients were reviewed and analyzed.Results:Type 1 TLM was performed in three patients, type 2a in one patient, type 3b in 12 patients, and type 4b in one patient. Negative surgical margins were achieved in all of the cases. Re-excision or any adjuvant treatment for positive resection margins was not required in any of the cases. Eight patients received adjuvant radiotherapy due to lymph node metastasis. Mean follow-up time was 33.8±15.7 months (range: 10–65 months). None of the patients had recurrence or distant metastasis.Conclusion:The transoral approach with the use of CO2 laser and microscopy offers complete tumor excision for treating supraglottic LSCC. The three-dimensional structure of the supraglottis can be achieved with adequate exposure. En bloc resection is possible with safe margins.

Introduction Management of the thyroid gland during laryngectomy has been controversial. The primary tumor may invade the thyroid gland by direct invasion or lymphovascular spread. Hypothyroidism and hypoparathyroidism are potential risks when lobectomy or total thyroidectomy are performed simultaneously. Objective To report the frequency of thyroid gland involvement by primary laryngeal squamous cell carcinoma in patients undergoing laryngectomy and to identify possible risk factors for thyroid gland involvement so that judicious excision of thyroid gland can be attained. Methods We performed a retrospective review of 9 years. Data was collected from medical records of patients dated from December 2009 to October 2018. All patients with laryngeal cancer who underwent laryngectomy with lobectomy or total thyroidectomy were included in the present study. Results We reviewed 151 laryngectomy records. A total of 130 surgeries included the thyroid gland with the excised specimen and were available for analysis. There were 124 males and 6 females. The mean age was 59.4 years old. The glottis was the most common subsite involved, in 70 patients, followed by 38 transglottic, 16 supraglottic and 03 subglottic tumors. On histology, 12 out of 130 excised thyroid glands were involved by squamous cell carcinoma. Only subglottic involvement (p=0.01) was significantly associated with thyroid gland invasion (TGI). Type of laryngectomy, subsite of the primary tumor, thyroid cartilage involvement, neck nodal metastases, and perineural and lymphatic invasion by the primary tumor were not associated with TGI. Conclusion Only subglottic involvement is associated with TGI; therefore, preoperative and intraoperative assessment is necessary prior to considering excision of the thyroid gland. [ABSTRACT FROM AUTHOR]

Introduction Management of the thyroid gland during laryngectomy has been controversial. The primary tumor may invade the thyroid gland by direct invasion or lymphovascular spread. Hypothyroidism and hypoparathyroidism are potential risks when lobectomy or total thyroidectomy are performed simultaneously. Objective To report the frequency of thyroid gland involvement by primary laryngeal squamous cell carcinoma in patients undergoing laryngectomy and to identify possible risk factors for thyroid gland involvement so that judicious excision of thyroid gland can be attained. Methods We performed a retrospective review of 9 years. Data was collected from medical records of patients dated from December 2009 to October 2018. All patients with laryngeal cancer who underwent laryngectomy with lobectomy or total thyroidectomy were included in the present study. Results We reviewed 151 laryngectomy records. A total of 130 surgeries included the thyroid gland with the excised specimen and were available for analysis. There were 124 males and 6 females. The mean age was 59.4 years old. The glottis was the most common subsite involved, in 70 patients, followed by 38 transglottic, 16 supraglottic and 03 subglottic tumors. On histology, 12 out of 130 excised thyroid glands were involved by squamous cell carcinoma. Only subglottic involvement (p = 0.01) was significantly associated with thyroid gland invasion (TGI). Type of laryngectomy, subsite of the primary tumor, thyroid cartilage involvement, neck nodal metastases, and perineural and lymphatic invasion by the primary tumor were not associated with TGI. Conclusion Only subglottic involvement is associated with TGI; therefore, preoperative and intraoperative assessment is necessary prior to considering excision of the thyroid gland.

Objective: Complete en bloc supraglottic tumor excision with transoral laser microsurgery (TLM) can be achieved with good postoperative outcomes. We report surgical feasibility and the postsurgical outcomes of en bloc resection of supraglottic laryngeal squamous cell carcinomas (LSCC) with TLM. Methods: Seventeen patients who underwent TLM for supraglottic laryngeal cancer were included in the study. Demographic and pathological data, clinic and follow-up outcomes of the patients were reviewed and analyzed. Results: Type 1 TLM was performed in three patients, type 2a in one patient, type 3b in 12 patients, and type 4b in one patient. Negative surgical margins were achieved in all of the cases. Re-excision or any adjuvant treatment for positive resection margins was not required in any of the cases. Eight patients received adjuvant radiotherapy due to lymph node metastasis. Mean followup time was 33.8±15.7 months (range: 10–65 months). None of the patients had recurrence or distant metastasis. Conclusion: The transoral approach with the use of CO2 laser and microscopy offers complete tumor excision for treating supraglottic LSCC. The three-dimensional structure of the supraglottis can be achieved with adequate exposure. En bloc resection is possible with safe margins. [ABSTRACT FROM AUTHOR]

Shuting Yu,1 Yingying Zhu,1 Xiaohua Shi,2 Ke Hu,3 Chunmei Bai,4 Wenwen Diao,1 Xiaoli Zhu,1 Zhiqiang Gao,1 Xingming Chen1 1Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Radiotherapy, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xingming Chen Tel +86 13901077778Email xingming.chen@hotmail.comPurpose: To date, no guidelines have been proposed for the ideal treatment of postoperative larynx squamous cell carcinoma (LSCC) patients with lymphovascular invasion due to a lack of similar studies. The present study was conducted to compare the survival and toxicity in LSCC patients with lymphovascular invasion receiving either postoperative radiotherapy (PORT) or postoperative chemoradiotherapy (POCRT). The results can be applied for more appropriate treatment of these patients.Patients and Methods: Three hundred eighty-eight eligible LSCC patients with lymphovascular invasion were enrolled in this retrospective study. Survival and treatment-related toxicities were compared in the POCRT and PORT group using propensity score matching (PSM) methodology (1:1).Results: Five-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of all patients were 48.7%, 58.2%, and 56.0%, respectively. Significantly, higher RFS rates (P=0.040) were found in the POCRT group than the PORT group in the PSM cohort. In the multivariate analysis, higher OS, DSS, and RFS rates were observed in the POCRT group than the PORT group (P=0.049, 0.024, and 0.011 respectively). Patients in the POCRT group presented more acute toxicities than those in the PORT group such as hematological toxicities (25.0% vs 0.9%, P< 0.001) and mucositis (35.0% vs 19.1%, P=0.002).Conclusion: In the context of no ideal treatment for LSCC patients with lymphovascular invasion, the present study proposes POCRT as a preferable modality compared with PORT, as POCRT was associated with higher RFS rates. Higher RFS, DFS, and OS rates were also observed in the POCRT group in the multivariate analysis.Keywords: head and neck carcinoma, larynx carcinoma, lymphovascular invasion, propensity score, chemoradiotherapy, survival

Objective: To investigate the expressions of MAPK10, c-Jun and Itga6 in laryngeal carcinoma and its influence on the sensitivity to docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy. Methods: Fifty-seven patients with supraglottic squamous cell carcinoma, who were treated by two cycles of TPF induction chemotherapy in our hospital, were enrolled in this study and divided into groups by chemotherapy resistance or chemotherapy sensitivity. The expressions of mRNA and protein of MAPK10, c-Jun and Itga6 in tumor tissues were evaluated by immunohistochemistry. The consistency of mRNA and protein expressions was tested, and the relation with the clinicopathological features was analyzed. Results: The positive rates of MAPK10 andc-Jun in the tumor tissues of the sensitive group were significantly higher than those of there assistant group, which was 90.48% and 100.00%, respectively. The expression rate of Itga6 was significantly higher in the resistant group, which was 83.33% (P 0.05). However, the expressions of MAPK10 and c-Jun were negatively correlated withclinical stage and pathological grading (P

Objective:The aim of this study was to prospectively evaluate and compare the outcomes in patients undergoing pharyngeal closure with the linear stapler and suture techniques after total laryngectomy.Methods:Forty-one patients who needed total laryngectomy for laryngeal cancer were enrolled in the study. Patients were randomized into two groups according to the pharyngeal closure technique: the linear stapler group (Group A) and the suture closure group (Group B). Rate of pharyngocutaneous fistula (PCF), nasogastric tube (NGT) removal time and pharyngeal closure time were analyzed and compared between the two groups.Results:PCF developed in three patients in Group A (14.3%) and in seven patients in Group B (35%). Although the rate of PCF was lower in Group A, this did not represent a statistical difference (p:0.129). Median NGT removal time was 12 days (IQR=3) and 19.5 days (IQR=1) in Groups A and B, respectively. Median NGT removal time was not statistically different between the two groups (p:0.642). All patients were able to swallow liquids and solids without difficulty. Median pharyngeal closure time was 3 minutes (IQR=1) and 37.5 minutes (IQR=9) in Groups A and B, respectively. Median pharyngeal closure time was significantly lower in Group A (p:0.00).Conclusion:The linear stapler technique in total laryngectomy is a reliable, safe, easy-to-apply and time-saving method. Closure with linear stapler significantly reduces pharyngeal closure time without adverse effect on NGT removal times and PCF rates.

Introduction: Viral diseases can have roles in oral cavity and larynx carcinoma. However, the relationship between HPV, herpetic infection and these cancers is not clear. Materials & methods: DNA of tissues from oral and larynx carcinoma was extracted and the presence of HPV, HSV-1, HSV-2, EBV, CMV and Varicella Zoster virus was detected. Results: We detected five HSV-1 in oral cavity cancer and two HSV-1 in larynx carcinoma. Also, four and two HPV-positive in oral cavity and larynx carcinoma were found, respectively. There were five HPV type 18 and one HPV type 31. None of our samples were infected with EBV, CMV, HSV-2 and Varicella Zoster virus. Conclusion: A higher prevalence of HPV and HSV-1 in cancerous tissues in comparison with normal ones was detected. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the increasing incidence of laryngeal squamous cell carcinoma (LSCC) in Algeria, scarce information is available on the importance of the preventable etiological factors which may drive the disease. Remarkably, a significant number of cases occur in nonsmoker and nondrinker patients; hence, suggesting that alternative risk factors, like Human papillomavirus (HPV), might be etiologically involved. To gain more insight on the risk factors associated with the disease in the country, we evaluated the etiological fraction of HPV in comparison to tobacco and alcohol intake in LSCC patients. Methods To evaluate the etiopathologic fraction (EF) for HPV compared to history of tobacco and alcohol in LSCC, HPV DNA presence in 46 invasive and 3 non-invasive formalin-fixed paraffin-embedded laryngeal tumors was screened using the SPF10-DEIA-LiPA25 Assay. Demographic data and information related to exposure to the risk factors were gathered through interviewer-assisted questionnaires. Results We observed that 40.8% of all LSCC cases were associated with smoking, 40.8% had combined tobacco and alcohol exposure history, and 14.3% did not show prior exposure to either risk factor. 1 out of 3 in-situ carcinoma cases was positive for HPV-6. HPV prevalence was null in the invasive tumors. HPV DNA was detected in 2.38% for all studied cases. 10.2% of LSCC patients did not associate with any of the studied risk factors. Conclusion Here we show that HPV etiological fraction in LSCC Algerian patients is low and smoking and alcohol remain the principal etiopathologic risk for LSCC burden in Algeria.

The purpose of the present work aimed at exploring the potential biochemical components and biological activities of an organic extract of the white truffle Tirmania nivea collected from the Iraqi desert, then test the organic extract against the Cytotoxicity on Human Larynx carcinoma cells and selected strains of pathogenic bacteria. Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry GC/MSS were used to analyze mycochemical compositions. The antibacterial activity and Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) was investigated using a disk diffusion agar method. The truffle extract's cytotoxicity effect against the larynx cell line (Hep-2) was assessed by the MTT assay (in vitro). FTIR results provided the presence of phenol, carboxylic acid, and alkane's functional group, The GC-MS analysis of T. nivea disclose the existence of nineteen compounds that can contribute to the pharmaceutical properties of the truffle. As for antibacterial activity result, A growth inhibition activity of truffle extract at (18-40 mm inhibition zones) against the tested pathogenic bacterial strains was detected, which minimum inhibitory concentration values ranged from 3.12 to 6.25 mg/mL for Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) Respectively. The results of cytotoxicity shown that the organic truffle extract exhibited a high inhibitory rate (52.685%) against cell line (Hep-2) at a concentration of 1.56 μg/mL. In this work, the results showed that the organic extracts of T. nivea are very promising as cancer cytotoxicity and antibacterial agent for future medical applications. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) have been associated with a subset of head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to determine the prevalence of HPV DNA in archived formalin‐fixed paraffin‐embedded tissue from patients with histologically confirmed HNSCCs in a South African cohort. A nested PCR was used for the detection of HPV DNA targeting the L1 gene. Positive samples were confirmed using an in‐house hemi‐nested PCR targeting the E6 gene and genotyped by sequence determination of amplicons. HPV DNA was detected in 57/780 (7.3%) samples, with the highest prevalence being in the sinonasal tract (16.0%) and oropharynx (10.8%). HPV16 was the most frequently detected type, being found in 26/57 (45.6%) positive samples. The prevalence of HPV DNA in HNSCCs found in this study was lower than that found in developed countries [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to prospectively evaluate and compare the outcomes in patients undergoing pharyngeal closure with the linear stapler and suture techniques after total laryngectomy. Methods: Forty-one patients who needed total laryngectomy for laryngeal cancer were enrolled in the study. Patients were randomized into two groups according to the pharyngeal closure technique: the linear stapler group (Group A) and the suture closure group (Group B). Rate of pharyngocutaneous fistula (PCF), nasogastric tube (NGT) removal time and pharyngeal closure time were analyzed and compared between the two groups. Results: PCF developed in three patients in Group A (14.3%) and in seven patients in Group B (35%). Although the rate of PCF was lower in Group A, this did not represent a statistical difference (p:0.129). Median NGT removal time was 12 days (IQR=3) and 19.5 days (IQR=1) in Groups A and B, respectively. Median NGT removal time was not statistically different between the two groups (p:0.642). All patients were able to swallow liquids and solids without difficulty. Median pharyngeal closure time was 3 minutes (IQR=1) and 37.5 minutes (IQR=9) in Groups A and B, respectively. Median pharyngeal closure time was significantly lower in Group A (p:0.00). Conclusion: The linear stapler technique in total laryngectomy is a reliable, safe, easy-to-apply and time-saving method. Closure with linear stapler significantly reduces pharyngeal closure time without adverse effect on NGT removal times and PCF rates. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to investigate if the flattening filter free (FFF) irradiation mode of a linear accelerator (linac) is advantageous as compared to the flat beam (FF) irradiation mode in intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for carcinoma of the hypopharynx / larynx. Methods Four treatment plans were created for each of 10 patients for an Elekta Synergy linac with Agility collimating device, a dual arc VMAT and a nine field step and shoot IMRT each with and without flattening filter. Plan quality was compared considering target coverage and dose to the organs at risk. All plans were verified by a 2D–ionization-chamber-array and delivery times were compared. Peripheral point doses were determined as a measure of second cancer risk. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Results Plan quality was similar for all four treatment plans without statistically significant differences of clinical relevance. The clinical goals were met in all plans for the PTV-SIB (V95% > 95%), the spinal cord (D1ccm

Here we report a 60 year aged male presented with complaints of right neck swelling of 3 months duration, swelling was initially small in size and gradually increasing. On examination right level II, hard mobile lymph node was palpable measuring 4 × 4 cm in size, oral cavity and oropharynx was normal. Computed tomography of face neck showed moderately enhancing soft tissue mass of 2 × 3 cm in the supra glottis and left level II cervical lymphadenopathy of size 5 × 5 cm with infiltrating into left sternomastoid muscle. Direct laryngoscopy revealed an ulcero proliferative growth in the supra glottis extending into vallaculla biopsy from the growth showed small round cells with scant amount of cytoplasm with hyperchromatic nucleus, atypical mitosis and at places rosettoid arrangement was seen. Immunohistochemistry with pancytokeratin, CD 56 and synaptophysin were positive, LCA was negative and Ki 67 was >70 %, features consisted with neuroendocrine carcinoma small cell type. Computed tomography of chest, abdomen and pelvis was normal. Finally it was labeled as localized neuro endocrine carcinoma small cell type of larynx (supraglottis). This patient treated with external beam radiotherapy 70 Gy in 35 fractions @ 2 Gy per fraction over 7 weeks along with concurrent chemotherapy with weekly cisplatin followed by adjuvant chemotherapy with Cisplatin and Etoposide for six cycles. [ABSTRACT FROM AUTHOR]

Introduction: Novel endoscopic technique - Narrow Band Imaging (NBI) seems to be a promising method for an early detection of neoplastic lesions of the upper aerodigestive tract. Compared to white light endoscopy, NBI improves the visualisation of the mucosal and submucosal microvascular patterns of observed pathologies. The aim of the study was to evaluate the diagnostic value of biopsy and NBI in patients with cancer of the larynx and hypopharynx. Material and methods: The study was conducted in 100 adult subjects hospitalized in the Clinic of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics of Military Medical Academy University Teaching Hospital in Lodz, who were planned for surgical procedures for excision or surgical biopsy of pathological lesions of the hypopharynx or larynx. The following examinations were performed: subjective and objective, otorhinolaryngological, NBI endoscopy and histopathological assessment of suspicious lesions. The microvascular pattern of observed lesions was assessed according to the Ni scale criteria. The next stage of the study was to compare the endoscopic examination results (type of vascular pattern according to the Ni scale) with the histopathological result. The obtained results were subjected to statistical analysis. Results: The sensitivity of NBI endoscopy in detection of malignant neoplasms in patients with hypopharynx and larynx lesions is 90.48%, specificity - 91.14%, positive predictive value - 73.08%, negative predictive value - 97.30%. Conclusions: NBI endoscopy is a modern imaging method, increasing the diagnostic potential of endoscopy in the early detection of malignant lesions within the hypopharynx and larynx. [ABSTRACT FROM AUTHOR]

Highlights • Cervical osteomyelitis is a serious but rarely reported complication following the treatment of pharyngeal cancer. • Cervical pain was the first sign to appear, sometimes 1 year before any other sign. • Cervical pain, fever, and/or neurological signs should lead to early imaging to confirm the diagnosis. • Early diagnosis and management improve the prognosis. Abstract Background Cervical osteomyelitis following the treatment of pharyngeal cancer with laryngectomy and chemoradiotherapy is poorly reported. Methods Six cases of cervical osteomyelitis occurring over a 1-year period are described herein. These are reviewed alongside four cases reported previously in the literature. Results Among the total 10 cases, the average age of the patients was 58.7 years. The period between laryngectomy and the diagnosis of cervical osteomyelitis was on average 3 years and 1 month and the male to female sex ratio was 9:1. Two patients had a history of cervical fistula with an esophageal prosthesis, one had a spontaneous cervical fistula, one had a pharyngeal cutaneous fistula, and one had an esophageal prosthesis without any fistula. At the time of diagnosis, seven had a history of cervical pain (70%) and nine had a neurological deficit (90%). Seven patients (70%) underwent surgery; one (10%) was contraindicated for a general anesthetic and two (20%) died before any intervention. The indication for surgery was a neurological deficit for six patients (60%) and the requirement for lavage and debridement for two patients (20%). The average length of antimicrobial treatment was 12.7 weeks. The outcome was favorable for six patients. Four patients died. Conclusions Cervical osteomyelitis is a serious but rarely reported complication following the treatment of pharyngeal cancer with chemoradiotherapy and laryngectomy. Cervical pain was the first sign to appear, sometimes 1 year before any other sign. Physicians should be aware of this dreaded complication, which is probably underdiagnosed and is related to an increased mortality rate. [ABSTRACT FROM AUTHOR]

Background: Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse. Objective: To evaluate prognostic factors of local relapse and local control with TLM (LC‐TLM). Methods: Local relapse and LC‐TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed. Results: Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64‐27.03; P < .001), paraglottic involvement (2.42, CI: 1.41‐4.15; P = .001), anterior commissure involvement (2.12, CI: 1.43‐3.14; P < .001), grade of differentiation (1.74, CI: 1.18‐2.57; P = .005), and alcohol consumption (1.4, CI: 0.99‐1.98; P = .057). Local relapse tended to inversely correlate with experience (0.73, CI: 0.51‐1.03; P = .078). The most important factors for local relapse were previous radiotherapy failure and anterior commissure involvement. LC‐TLM inversely correlated with previous radiotherapy failure (0.09, CI: 0.03‐0.28; P < .001), paraglottic involvement (0.25, CI: 0.14‐0.43; P < .001), anterior commissure involvement (0.49, CI: 0.32‐0.77; P = .007), margins (0.56, CI: 0.30‐1.04; P = .068), and differentiation (0.68, CI: 0.44‐1.05; P = .087). LC‐TLM correlated with experience (1.71, CI: 1.13‐2.55; P = .010). The most important factors for LC‐TLM were previous radiotherapy failure and paraglottic involvement. Conclusion: Previous radiotherapy failure is the most important factor for local relapse and LC‐TLM. In primary treatments, anterior commissure involvement and paraglottic involvement are the most important factors for local relapse and LC‐TLM, respectively. [ABSTRACT FROM AUTHOR]

Larynx cancer in young pregnant women is very uncommon. The treatment modalities traditionally used for larynx cancer management may present high risk either for the mother or the fetus. A rational therapeutic approach (flexible endoscopic laser surgery), that allows avoiding the risk of radiation therapy and general anesthesia, is presented. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms of the larynx are rare but are the most common nonsquamous tumors of this organ. There are 4 different types of laryngeal neuroendocrine tumors composed of paraganglioma, typical carcinoid, atypical carcinoid tumor, and small cell neuroendocrine carcinoma. Carcinoids and small cell neuroendocrine carcinomas are epithelial neoplasms, whereas paragangliomas are of neural origin. Diagnosis is based primarily on light microscopy and confirmed by immunohistochemistry and electron microscopy. Precise diagnosis is essential because the natural history, treatment, and prognosis vary widely for the different neoplastic categories. Typical carcinoids are very rare and are treated by wide local excision, usually partial laryngectomy, without elective neck dissection. Atypical carcinoid tumors are more common and more aggressive. They are treated by partial or total laryngectomy with elective or therapeutic neck dissection. Adjuvant chemo/radiotherapy may be of benefit in some cases. Small cell neuroendocrine carcinomas are highly aggressive and should be considered disseminated at initial diagnosis. The treatment is by irradiation and chemotherapy as surgery has proven to be of a little benefit. Paragangliomas are treated by local excision or partial laryngectomy.

OBJECTIVE: Larynx carcinoma is a common head-neck malignant tumor. Recent investigations showed the involvement of microRNA (miR) in regulation of multiple tumors. miR-140-5p showed decreased expression in various cancers, but without knowledge regarding its expression in larynx carcinoma and effects on cell invasion and angiogenesis. MATERIALS AND METHODS: Real-time quantitative PCR was firstly employed to measure miR- 140-5p expression in larynx carcinoma and controlled tumor adjacent tissues. In larynx cancer cell line, agomir or antagomir of miR-140-5p was applied to up-regulate or down-regulate miR-140-5p, respectively. Western blot was used to evaluate vascular endothelial growth factor A (VEGF-A) expression, and cell proliferation was modified by 3-(4,5-dimethyl- 2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) approach. Transwell approach was used to measure cell invasion, and angiogenesis assay was used to detect the effect on angiogenesis. Luciferase report assay (LRA) measured targeting binding between miR-140-5p and VEGF-A. RESULTS: Comparing to tumor adjacent tissues, larynx carcinoma cells showed significantly decreased miR-140-5p expression. Agomir up-regulated miR-140-5p expression and weakened proliferation and invasion potency, and inhibited angiogenesis. Antagomir down-regulated miR-140-5p and presented the opposite results. Finally, LRA confirmed direct binding between miR-140-5p and VEGF-A. CONCLUSIONS: MiR-140-5p can target VEGF-A in larynx carcinoma cell line to inhibit cell invasion and angiogenesis. MiR-140-5p thus may work as the direct molecular target of larynx carcinoma. [ABSTRACT FROM AUTHOR]

Laryngeal neoplasm contributes to 30-40% of carcinomas of the head and neck. Mast cells are normal connective tissue residents, well represented in the respiratory tract. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. The aim of this study was to evaluate the correlation between mast cell density, microvascular density, histopathological type and histological grade. Our study included 38 laryngeal carcinomas as follows: adenoid cystic carcinoma (2 cases), malignant papilloma (2 cases) and squamous cell carcinoma (34 cases). The combined technique of CD 34-alcian blue safranin (ABS) was used to identify microvessel and mast cell density, which was quantified by the hot spot method. A significant correlation was found between both mast cell and microvascular density, and G1/G2 histological grade (p=0.002 and p=0.004, respectively). Squamous cell carcinoma was significantly correlated with mast cell density (p=0.003), but not with microvascular density (p=0.454).

Background: The aim of this study was to investigate if the flattening filter free (FFF) irradiation mode of a linear accelerator (linac) is advantageous as compared to the flat beam (FF) irradiation mode in intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for carcinoma of the hypopharynx / larynx.Methods: Four treatment plans were created for each of 10 patients for an Elekta Synergy linac with Agility collimating device, a dual arc VMAT and a nine field step and shoot IMRT each with and without flattening filter. Plan quality was compared considering target coverage and dose to the organs at risk. All plans were verified by a 2D-ionization-chamber-array and delivery times were compared. Peripheral point doses were determined as a measure of second cancer risk. The Wilcoxon test was used for statistical analysis with a significance level of 0.05.Results: Plan quality was similar for all four treatment plans without statistically significant differences of clinical relevance. The clinical goals were met in all plans for the PTV-SIB (V95% > 95%), the spinal cord (D1ccm < 45 Gy) and the brain stem (D1ccm < 48 Gy). For the parotids, the goal of D50% < 30 Gy was met in 70% and 60% of the plans for the left and right parotid respectively, and the V95% of the SIB reached an average of 94%. Delivery times were similar for FF and FFF and significantly decreased by around 70% for VMAT as compared to IMRT. Peripheral doses were significantly reduced by 18% in FFF mode as compared to FF and by 26% for VMAT as compared to IMRT. Lowest peripheral doses were found for VMAT FFF, followed by VMAT FF.Conclusions: The FFF mode of a linear accelerator is advantageous for the treatment of hypopharynx/larynx carcinoma only with respect to reduction of second cancer induction in peripheral organs for the combination of Elekta Synergy linacs and Oncentra® External Beam v4.5 treatment planning system. This might be of interest in a therapy with curative intent. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the potential prognostic roles of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width (RDW) in patients with laryngeal squamous cell carcinoma (LSCC). 81 patients who underwent surgery for the larynx carcinoma were enrolled in the study. NLR, PLR and RDW were used as outcome measures. Local recurrence was detected in 30 (37.0 %) patients and neck lymph node metastasis was detected 6 (7.4 %) patients during follow-up period. Mortality was seen in 7 (8.6 %) patients. The mean PLR in the T1 and T2 stage tumors were significantly lower than the T4 stage. The mean RDW and PLR were significantly higher in the exitus group than the survivor group. The mean NLR in the patients with local recurrence was significantly higher than the non-recurrent patients. Progression-free survival (PFS) was lower in patients with high NLR. When analyzed by the Cox regression analysis of factors affecting the local recurrence, NLR was found to significantly affect the recurrence. According to ROC analysis for mortality, NLR was not found to be a prognostic factor, although the PLR and RDW were significant prognostic factors. According to Cox regression analysis, a high PLR increases mortality 4.2 times and a high RDW 4.6 times. Although in univariate analysis MCV, RDW and tumor grade were predictors of mortality, RDW and tumor grade independent predictors were found. Further studies involving large patient groups are required. [ABSTRACT FROM AUTHOR]

Open partial laryngectomies still play an important role in contemporary conservative management of laryngeal cancer. A comprehensive and systematic classification of open partial horizontal laryngectomies (OPHLs) was presented by the European Laryngological Society working committee in 2014. The aim of this video is to show the main surgical steps in OPHL using a cadaveric dissection and to explain the modular approach for removal of laryngeal tumors. [ABSTRACT FROM AUTHOR]

Objectives:Surgery is the first choice at the surgical treatment of laryngeal carcinoma. It is advised in the literature to perform thyroidectomy in addition to laryngectomy if the primary tumor advances to subglottic region or invades extralaryngeal tissues. But, hypothyroidism may be established especially after radiotheraphy. We aimed to evaluate thyroidectomy indications during laryngeal surgery under the guidance of literature.Methods:Invasion of thyroid gland from the primary tumor has been examined from the medical records of 44 patients who had been operated because of laryngeal carcinoma at Haydarpafla Numune Education and Training Hospital between February 2002 and February 2007.Results:Only, 1 patient had thyroid gland invasion. The TNM status of the patient was T4aN3, stage 4b with a 10 mm subglottic extension.Conclusion: Thyroidectomy must be performed during laryngeal surgery only at the specific cases carrying the criteria of having subglottic and transglottic extension of the primary tumor, having thyroid gland mass with the palpation, and the tumors invading thyroid cartilage.

Background: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. Methods: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. Results: ALDH1 expression was detected in 17.5 % (10/57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1−. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 + group versus 48.9 % for ALDH1− patients ( p = 0.034). Conclusion: The patients in this study with ALDH1 + tumours had better outcomes than their counterparts with ALDH1− tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed. [ABSTRACT FROM AUTHOR]

Objective: In laryngeal cancer the most suspected regions of invasion are preepiglottic space (PES), anterior commissure (AC), thyroid cartilage (TC), subglottic region (SR) and extralaryngeal spread (ELS). The objective of this study is to compare the results of preoperative computed tomography (CT) with postoperative histopathologic analysis in these critical regions for the total or partial laryngectomy. Methods: Eighty-nine patients, who had undergone total laryngectomy with a diagnosis of laryngeal cancer reported that squamous cell cancer (SCC) between 2005 and 2013, were reviewed retrospectively. All the patients, after the first application done total laryngectomy before flexible laryngoscopy, computed tomography for the neck and endoscopic biopsy with direct laryngoscopy. Histopathological results of PES, AC, TC, ELS and SR invasion are compared to preoperative CT findings and determined of specificity, sensitivity, false negative and false positive results and rate of accuracy. Results: All the patients were male, median age was 67 (range: 48 to 81) years. Fifty-six patients were in T4 and 33 patients in T3 stage. Compared to results between positive CT findings and negative histopathological examination; PES invasion in 41 patients/ 5 patients, AC invasion was found in 38/ 15 patients, TC invasion in 28/16 patients, SR invasion in 49/ 9 patients and ELS invasion in 25 /7 patients. Accuracy rate of computed tomography in these regions are 85%, 64%, 76%, 79%, and 83%, respectively. All the results especially thyroid cartilage invasion were statistically significant. Conclusion: In all regions invasion, CT has a low diagnostic reliability in high-grade laryngeal cancer in our study. We suggested that histopathological results are the gold standard intraoperatively for determining total or partial laryngectomy. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Epithelial-to-mesenchymal transition (EMT) consists of a rapid and reversible change in the cellular phenotype toward the mesenchymal cell phenotype that facilitates cell migration and invasion of the tumor into surrounding tissues followed by metastasis. In the present study, we sought to determine the clinical significance of E-cadherin, N-cadherin, β-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin in a cohort of patients with stage I to IVA laryngeal squamous cell carcinoma (LSCC) treated with surgery with or without adjuvant therapy using immunohistochemical analyses.Study Design: Individual retrospective cohort study.Methods: E-cadherin, N-cadherin, β-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated in a cohort of 82 patients with stages I to IVA LSCC. The Fisher exact test was used for categorical variables, and the Mann-Whitney test where appropriate for continuous variables. Survival comparisons was performed using the log-rank test. A multivariate analysis using the Cox proportional hazards model was performed and considered all EMT markers.Results: In multivariate analysis, T stage was an independent risk factor for adverse disease-specific survival (DSS) and overall survival (OS) (P = .025 and .019, respectively). Cytoplasmic β-catenin overexpression was independently associated with a longer DSS (P = .0007), and E-cadherin overexpression was found to be an independent risk factor for poor OS (P = .030).Conclusions: E-cadherin and β-catenin pathways could represent future therapeutic targets in the treatment of LSCC. However, validation of our results in prospective cohorts of patients with LSCCs is required before their clinical implementation.Level Of Evidence: NA. [ABSTRACT FROM AUTHOR]

We studied the expression of p16 in a series of HPV-negative laryngeal squamous cell carcinomas and assessed its association with prognosis. Forty-five patients with laryngeal carcinoma were included in the study. Clinicopathological features and prognosis were reviewed. p16 protein expression was analysed through immunohistochemistry. We analysed messenger RNA (mRNA) in 25 cases through quantitative reverse transcription polymerase chain reaction. HPV status was assessed by PCR using three different protocols based on MY09/11 and GP5/6 primers. Four out of 45 (9 %) cases overexpressed p16 protein and showed a tendency to worse survival that was significant for stages I-III (log-rank p value = 0.001). Expression of p16 mRNA was high in 12 out of 25 (48 %) cases using an arbitrary cut-off level. All tumours were HPV negative with all three detection methods. A CDKN2A mutation was found in eight cases. One case with a missense and one with a frameshift mutation showed p16 protein expression by immunohistochemistry. Six out of seven (86 %) mutated but only 6 out of 18 (33 %) non-mutated cases presented p16 mRNA overexpression ( p = 0.03). Our findings suggest that p16 overexpression, both at protein and mRNA levels, may reflect CDKN2A genetic alterations in HPV-negative laryngeal squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

The molecular mechanism underlying cancer invasiveness and metastasis of larynx carcinoma remains elusive. Here we reported a strong correlation between phosphorylated epidermal growth factor receptor (EGFR) and matrix metalloproteinase-7 (MMP7) levels in larynx carcinoma patients. To examine whether a causal link exists, we used a human larynx carcinoma line, Hep-2, to study the molecular basis of EGFR signaling and MMP7 activation. We found that EGF-induced EGFR phosphorylation in Hep-2 cells resulted in activation of MMP7 and, consequently, an increase in cancer invasiveness. An EGFR inhibitor efficiently blocked this EGF-induced activation of MMP7. Moreover, an inhibitor for PI3 kinase (PI3K)/Akt, but not an inhibitor for mitogen-activated protein kinase (MAPK) or an inhibitor for c-Jun N-terminal kinase (JNK), significantly inhibited the EGF-induced activation of MMP7, suggesting that PI3K/Akt signaling cascades may be responsible for EGF-activated MMP7. Further dissection of the pathway revealed that nuclear exclusion of Akt downstream target, FoxO1, was induced by EGF-induced Akt activation and could be inhibited by either the EGFR inhibitor or by the PI3K/Akt inhibitor. Expression of a constitutive nuclear form of FoxO1 significantly inhibited MMP7 activation induced by EGF. Taken together, these findings suggest that EGF/EGFR signaling activates downstream PI3K/Akt to induce FoxO1 nuclear exclusion, which activates MMP7 to promote larynx carcinoma metastasis. Thus, Akt and FoxO1 appear to be promising therapeutic targets for preventing the metastasis of larynx carcinoma. [ABSTRACT FROM AUTHOR]

Cancer neovascularization plays a key role in the metastasis of larynx carcinoma. However, the molecular mechanism for the neovascularization control in larynx carcinoma is poorly understood. Since placental growth factor (PLGF) has been reported to be involved in pathological angiogenesis, and since matrix metalloproteinases (MMPs) are essential for extracellular matrix degradation during neovascularization, here we were prompted to examine whether PLGF and MMPs may play a coordinate role in the metastasis of larynx carcinoma. Our data showed that the expression of PLGF and MMP3 strongly correlated in the larynx carcinoma in the patients, and significant higher levels of PLGF and MMP3 were detected in the larynx carcinoma from the patients with metastasis of the primary cancer. Thus, we used a human larynx carcinoma cell line, Hep-2, to examine whether expression of PLGF and MMP3 may affect each other. We found that overexpression of PLGF in Hep-2 cells increased expression of MMP3, while inhibition of PLGF in Hep-2 cells decreased expression of MMP3. However, neither overexpression, nor inhibition of MMP3 in Hep-2 cells affected the expression level of PLGF. These data suggest that PLGF may function upstream of MMP3 in larynx carcinoma cells. We then analyzed how PLGF affected MMP3. Application of a specific ERK1/2 inhibitor to PLGF-overexpressing Hep-2 cells substantially abolished the effect of PLGF on MMP3 activation, suggesting that PLGF may increase expression of MMP3 via ERK/MAPK signaling pathway. Since anti-PLGF was recently applied in clinical trials to inhibit cancer-related angiogenesis, here our data further demonstrate that inhibition of cancer neovascularization by anti-PLGF is mediated not only by direct effect on endothelial growth and capillary permeability, but also by indirect effect via MMP3 on the extracellular matrix degradation in larynx carcinoma. [ABSTRACT FROM AUTHOR]

The abnormal expression of microRNAs (miRNAs) plays a key role in tumorigenesis. In order to identify potential miRNA biomarkers for early diagnosis of larynx carcinoma, we employed a miRNA microarray technique and applied bioinformatic algorithms to characterize miRNA classifiers in early larynx carcinoma and normal esophageal mucosa tissue samples from 69 patients who were selected retrospectively for this study. We identified 47 miRNAs that were significantly differentially expressed in primary larynx tumor tissues compared to normal tissues using a SAM algorithm. Of these, 30 were up-regulated and 17 down-regulated in early larynx cancer, including hsa-miR-657, which was overexpressed, and hsa-miR-1287, which was underexpressed. These two candidate miRNA biomarkers were combined as a single classifier to recognize the biological characteristics in early larynx carcinoma. Real-time quantitative reverse-transcription PCR validated the microarray results in both trial and test samples. The hsa-miR-657-hsa-miR-1287 classifier displayed high sensitivity and specificity for discriminating between early larynx carcinoma and normal mucosa tissues, suggesting they may be suitable as potential predictive biomarkers for the early diagnosis of larynx carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: For several decades, conventional histological staining and immunohistochemistry (IHC) have been the main tools to visualize and understand tissue morphology and structure. IHC visualizes the spatial distribution of individual protein species directly in tissue. However, a specific antibody is required for each protein, and multiplexing capabilities are extremely limited, rarely visualizing more than two proteins simultaneously. With the recent emergence of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-imaging), it is becoming possible to study more complex proteomic patterns directly in tissue. However, the analysis and interpretation of large and complex MALDI-imaging data requires advanced computational methods. In this paper, we show how the recently introduced method of spatial segmentation can be applied to analysis and interpretation of a larynx carcinoma section and compare the spatial segmentation with the histological annotation of the same tissue section. Methods: Matrix-assisted laser desorption/ionization imaging is a label-free spatially resolved analytical technique, which allows detection and visualization of hundreds of proteins at once. Spatial segmentation of the MALDI-imaging data by clustering of spectra by their similarity was performed, automatically generating spatial a segmentation map of the tissue section, where regions of similar proteomic patterns were highlighted. The tissue was stained with the hematoxylin and eosin (H&E), histopathologically analyzed and annotated. The segmentation map was interpreted after its overlay with the H&E microscopy image. Results: The automatically generated segmentation map exhibits high correspondence to the detailed histological annotation of the larynx carcinoma tissue section. By superimposing, the segmentation map based on the proteomic profiles with H&E-stained microscopic images, we demonstrate precise localization of complex and histopathologically relevant tissue features in an automated way. Conclusions: The combination of MALDI-imaging and automatic spatial segmentation is a useful approach in analyzing carcinoma tissue and provides a deeper insight into the functional proteomic organization of the respective tissue. [ABSTRACT FROM AUTHOR]