A Systematic Review Evaluating the Diagnostic Efficacy of Narrow-Band Imaging for Laryngeal Cancer Detection.

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.

The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma.

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.

YAP/STAT3 promotes the immune escape of larynx carcinoma by activating VEGFR1-TGFß signaling to facilitate PD-L1 expression in M2-like TAMs.

Larynx carcinoma (LC) is the most prevalent head and neck cancer among adults. LC xenograft mouse model was generated to verify the effect of VEGF on macrophage polarization and tumor growth in vivo. EdU assay was performed to measure the cell proliferation. Transwell assay was applied to assess cell migration. The expression of YAP and STAT3 was also significantly increased in LC tumor tissues. Moreover, both YAP and STAT3 overexpression in LC cells promoted the proliferation, migration, as well as the secretion of PD-L1 in M2-like TAMs. Mechanistically, the interaction between YAP and STAT3 facilitated the transcription of VEGF. Moreover, with a co-culture system, VEGF secretion in LC cells enhanced PD-L1 expression in M2-like TAMs via activating VEGFR1-TGFß signaling pathway. Furthermore, VEGF secreted from LC cells also promoted the tumor growth of LC in vivo. We revealed that dysregulated YAP/STAT3 activity in LC cells could enhance the secretion of VEGF, which then functioned on M2-like TAMs via activating VEGFR1-TGFßß pathway to promote the expression of PD-L1 and immunosuppressive function of M2-like TAMs. Therefore, VEGF and PD-L1 might have a pivotal crosstalk between M2-like TAMs and LC cells, which provided a novel therapeutic target in regulating the metastasis of LC in future.

Human papillomavirus DNA in head and neck squamous cell carcinomas in the Free State, South Africa.

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.

Antimicrobial, antioxidant and anticancer activities of Laurencia catarinensis, Laurencia majuscula and Padina pavonica extracts.

The antimicrobial, antioxidant, and anticancer activities of ethanolic extract of Laurencia catarinensis, L. majuscula and Padina pavonica were determined. The highest antibacterial activity; 23.40 ±â€¯0.58 mm (00.98 µg/ml) and 22.60 ±â€¯2.10 mm (03.90 µg/ml) were obtained against Klebsiella pneumonia by Laurencia catarinensis and Padina pavonica, respectively. However, Padina pavonica showed excellent antibacterial activity against Bacillus subtilis (21.7 ±â€¯1.5 mm; 1.95 µg/ml), Staphylococcus aureus (21.7 ±â€¯0.58 mm; 1.95 µg/ml), Streptococcus pyogenes (20.7 ±â€¯1.2 mm; 1.95 µg/ml) and Acinetobacter baumannii (20.1 ±â€¯1.2 mm; 3.9 µg/ml). Moreover, the highest antifungal activity; 24.7 ±â€¯2.0 mm (0.98 µg/ml), 23.7 ±â€¯1.5 mm (0.98 µg/ml), 23.6 ±â€¯1.5 mm (0.98 µg/ml) was obtained by Padina pavonica against Candida tropicalis, C. albicans and Aspergillus fumigatus, respectively. The algal extracts showed DPPH radical scavenging activity in a concentration-dependent manner with maximum scavenging activity (77.6%, IC50 = 5.59 µg/ml and 77.07%, IC50 = 14.3 µg/ml) was provided by Padina pavonica and Laurenica majuscula, respectively. The in vitro antitumor activity revealed that the IC50 values of Padina pavonica were 58.9, 115.0, 54.5, 59.0, 101.0, 101.0, and 97.6 µg/ml; Laurencia catarinensis were 55.2, 96.8, 104.0, 78.7, 117.0, 217.0, 169.0 µg/ml; and Laurencia. majuscula were 115.0, 221.0, 225.0, 200.0, 338.0, 242.0, and 189.0 µg/ml; respectively against A-549 (Lung carcinoma), Caco-2 (Intestinal carcinoma), HCT-116 (Colon carcinoma), Hela (Cervical carcinoma), HEp-2 (Larynx carcinoma), HepG-2 (Hepatocellular carcinoma), and MCF-7 (Breast carcinoma) cell lines.

The pre-treatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red cell distribution width predict prognosis in patients with laryngeal carcinoma.

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.

Role of miR-138 in the regulation of larynx carcinoma cell metastases.

The cases of larynx carcinoma (LC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the LC metastases may provide novel therapeutic targets for LC treatment. Here, we studied the LC specimens from the patients and found that the levels of miR-138 were significantly decreased and the levels of ZEB2, a critical factor that regulates cancer cell invasiveness, were significantly increased in LC, compared to the paired normal larynx tissue. Metastatic LC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in LC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-untranslated region (3'-UTR) of ZEB2 mRNA to inhibit its translation, which was confirmed in a luciferase reporter assay. Further, miR-138 overexpression inhibited ZEB2-mediated cell invasiveness, while miR-138 depletion increased ZEB2-mediated cell invasiveness in LC cells. Together, our data suggest that miR-138 suppression in LC cells may promote ZEB2-mediated cancer metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of LC.

A metachronous second primary lung cancer after laryngectomy for laryngeal carcinoma.

A combination of laryngeal carcinoma and subsequent primary lung cancer is rare yet important in terms of therapeutic strategy and prognosis.

Frequency of Thyroid Gland Invasion by Laryngeal Squamous Cell Carcinoma: The Role of Subglottic Extension.

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.

Modular Approach to Open Partial Horizontal Laryngectomy: Step-by-Step Anatomic Dissection.

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.

En Bloc Resection of Supraglottic Carcinomas with Transoral Laser Microsurgery.

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.

Previously published ethno-pharmacological reports reveal the potentiality of plants and plant-derived products used as traditional home remedies by Bangladeshi COVID-19 patients to combat SARS-CoV-2.

Several plants have traditionally been used since antiquity to treat various gastroenteritis and respiratory symptoms similar to COVID-19 outcomes. The common symptoms of COVID-19 include fever or chills, cold, cough, flu, headache, diarrhoea, tiredness/fatigue, sore throat, loss of taste or smell, asthma, shortness of breath, or difficulty breathing, etc. This study aims to find out the plants and plant-derived products which are being used by the COVID-19 infected patients in Bangladesh and how those plants are being used for the management of COVID-19 symptoms. In this study, online and partially in-person survey interviews were carried out among Bangladeshi respondents. We selected Bangladeshi COVID-19 patients who were detected Coronavirus positive (+) by RT-PCR nucleic acid test and later recovered. Furthermore, identified plant species from the surveys were thoroughly investigated for safety and efficacy based on the previous ethnomedicinal usage reports. Based on the published data, they were also reviewed for their significant potentialities as antiviral, anti-inflammatory, and immunomodulatory agents. We explored comprehensive information about a total of 26 plant species, belonging to 23 genera and 17 different botanical families, used in COVID-19 treatment as home remedies by the respondents. Most of the plants and plant-derived products were collected directly from the local marketplace. According to our survey results, greatly top 5 cited plant species measured as per the highest RFC value are Camellia sinensis (1.0) > Allium sativum (0.984) > Azadirachta indica (0.966) > Zingiber officinale (0.966) > Syzygium aromaticum (0.943). Previously published ethnomedicinal usage reports, antiviral, anti-inflammatory, and immunomodulatory activity of the concerned plant species also support our results. Thus, the survey and review analysis simultaneously reveals that these reported plants and plant-derived products might be promising candidates for the treatment of COVID-19. Moreover, this study clarifies the reported plants for their safety during COVID-19 management and thereby supporting them to include in any future pre-clinical and clinical investigation for developing herbal COVID-19 therapeutics.

Screening of molecular markers of induced chemotherapy in supraglottic laryngeal squamouscell carcinoma.

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). The mRNA levels of MAPK10 and c-Jun were significantly lower in the resistant group than in the sensitive group, whilethemRNA levelof Itga6was significantly higher in the resistant group (P < 0.05). The protein expressions of MAPK10, c-Jun and Itga6 were consistent with their mRNA expressions (P < 0.05). The expressions of MAPK10, c-Jun and Itga6 were not correlatedwithage, gender and tumor diameter (P > 0.05). However, the expressions of MAPK10 and c-Jun were negatively correlated withclinical stage and pathological grading (P < 0.05). Negative correlations between MAPK 10 and Itga6, and between c-Jun and Itga6in tumor tissues were found by Spearman'srank correlation coefficient (P < 0.05). The correlation was also negative in the resistant tumor tissues (P < 0.05). CONCLUSION: The MAPK10 and c-Jun expressions were down-regulated, while the Itga6 expression was up-regulated in the chemo-resistant laryngeal carcinoma, and the expression levels of different factors were correlated witheach other. These factorsmight be important biomarkers for predicting outcomes of TPF chemotherapy in laryngeal carcinoma in the future.

Postoperative Concurrent Chemoradiotherapy versus Postoperative Radiotherapy Alone for Larynx Squamous Cell Carcinoma Patients with Lymphovascular Invasion: A Propensity Score Matching Study.

PURPOSE: 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.

Comparative evaluation of the diagnostic value of biopsy and NBI endoscopy in patients with cancer of the hypopharynx and larynx.

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%. C onclusions: 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.

Small-Cell Neuroendocrine Tumor of Larynx: A Rare Presentation.

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.

The Comparative Analysis of Suture versus Linear Stapler Pharyngeal Closure in Total Laryngectomy: A Prospective Randomized Study.

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.

Cervical osteomyelitis: A new identity of dreaded complication following pharyngeal cancer treatment.

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 1year before any other sign. Physicians should be aware of this dreaded complication, which is probably underdiagnosed and is related to an increased mortality rate.

Salvage radiotherapy for recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) after first-line treatment with surgery alone: a 10-year single-centre experience.

PURPOSE: Salvage surgery of recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) results in limited local control and survival rates. As a result of recent technological progress, radiotherapy (RT) has become a valuable, potentially curative therapeutic option. Thus, we aimed to determine prognostic factors for survival outcome in order to optimize patient selection for salvage radiotherapy after failure of first-line treatment with surgery alone in this special patient cohort. METHODS: Seventy-five patients (85% male, median age of 64 years) underwent salvage RT in a secondary setting for recurrent hypopharyngeal or laryngeal SCC after prior surgery alone between 2007 and 2017. On average, patients were treated with one prior surgery (range 1-4 surgeries). Median time between surgery and salvage RT was 7 months (range 1-47 months) for initially advanced tumors (T3/4, N+, extracapsular spread) and 18 months (range 5-333 months) for initially early stage tumors. The majority of patients received concomitant chemotherapy (n = 48; 64%) or other kind of systemic treatment concurrent to radiotherapy (n = 10; 13%). RESULTS: Median follow-up was 41 months (range 3-120 months). Overall, fifteen patients were diagnosed with local failure (all were in-field) at last follow-up (20%). Median time to recurrence was 35 months (range 3-120 months) and 3-year local progression-free survival (LPFS) was 75%, respectively. Dose-escalated RT with 70.4 Gy applied in 2.1 Gy or 2.2 Gy fractions corresponding an EQD2 > 70 Gy (p = 0.032) and the use of concomitant cisplatin weekly chemotherapy (p = 0.006) had a significant positive impact on LPFS. 3-year OS and DPFS were 76 and 85%, respectively. No toxicity-related deaths occurred. Reported grade > 3 side effects were rare (n = 4/70, 6%). CONCLUSION: Salvage radiotherapy resulted in excellent local control rates while radiation dose and the use of cisplatin weekly chemotherapy were identified as prognostic factors for LPFS. Nevertheless, patient selection for curative salvage treatment remains challenging.

Modulation of Mitochondrial and Epigenetic Targets by Polyphenols-rich Extract from Araucaria angustifolia in Larynx Carcinoma.

BACKGROUND: Araucaria angustifolia extract (AAE) is a polyphenol-rich extract that has gained interest as a natural anticancer agent. Recent work suggests that AAE induces oxidative damage and apoptosis through its action on decreasing complex I activity of the mitochondrial Electron Transport Chain (ETC). AIMS AND METHODS: In the present study, we aimed to further examine the specific targets by which AAE exerts proapoptotic effects in HEp-2 cancer cells. Specifically, the effect of AAE on the: 1) levels of pyruvate dehydrogenase was assessed by ELISA assay; 2) levels of mitochondrial ETC complexes, focusing on complex I at the gene transcript and protein level relevant to ROS generation was evaluated by multiplex ELISA followed by qRT-PCR and immunoblotting; 3) mitochondrial network distribution analysis was assessed by MitoTracker Red CMXRos; and 4) chemical variations on DNA was evaluated by dot-blotting in HEp-2 cells. RESULTS: Results demonstrated that AAE increased protein levels of PDH, switching energy metabolism to oxidative metabolism. Protein expression levels of complex I and III were found decreased in AAE-treated HEp-2 cells. Analyzing the subunits of complex I, changes in protein and gene transcript levels of NDUFS7 and NDUFV2 were found. Mitochondria staining after AAE incubation revealed changes in the mitochondrial network distribution. AAE was able to induce DNA hypomethylation and decreased DNA (cytosine-5)-methyltransferase 1 activity. CONCLUSION: Our data demonstrate for the first time that AAE alters expression of NDUFS7 and NDUFV2 mitochondrial subunits and induce epigenetic changes in HEp-2 cancer cells leading to a possible suppression of oncogenes.