Hypopharyngeal Tumors Research Articles

Lateral hypopharyngectomy with laryngeal preservation reconstructed with inlay fascio-cutaneous free flaps: clinical and functional outcomes.

Lateral hypopharyngectomy (LH) is one of the organ-preservation surgical strategies available for treatment of selected naïve early squamous cell carcinoma (SCC), as well as for rarer non-SCC tumours and persistent/recurrent/second primaries after chemoradiation of the lateral wall of the piriform sinus. Its reconstructive methods have been the subject of different approaches without a general consensus. The aim of the present study is to describe a retrospective series of LH reconstructed by inlay fascio-cutaneous free flaps, reporting on oncological and functional outcomes. Patients who underwent LH at the Department of Otorhinolaryngology - Head and Neck Surgery of the University of Brescia, Italy, between 2017 and 2023 were retrospectively reviewed. Clinical history, tumour histotype, postoperative complications, functional, and oncological outcomes were collected. Seven patients (6 males, 1 female) were included. In all, 29% had a naïve neoplasm, while 71% had recurrent disease. The final histology included 3 SCC, 2 synovial sarcomas, one liposarcoma, and one single-site mucosal metastasis from cutaneous melanoma. Negative margins were achieved in 6 patients (86%). All patients had swallowing rehabilitation by speech therapists and were able to safely eat a free diet at discharge, except for one who needed a percutaneous endoscopic gastrostomy to support nutritional oral intake. After a mean follow-up of 34.3 months, all patients except one are alive. Our study showed that, in selected cases, it is possible to radically remove lateral hypopharyngeal tumours with laryngeal preservation and free flaps inlay reconstruction, with a low rate of complications and acceptable functional and oncological results.

Non-peripheral octasubstituted zinc(II) phthalocyanines bearing pyridinepropoxy substituents – Antibacterial, anticancer photodynamic and sonodynamic activity

The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran – DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications.

Elective vs. emergency tracheotomy complications in advanced hypopharyngeal cancer.

Squamous cell carcinoma of the hypopharyngeal region is a rare, aggressive disease with a poor prognosis and a high mortality rate, and represents up to 95% of all hypopharyngeal tumors. Patients with upper aerodigestive tract tumors can develop airway compromise before or during chemoradiotherapy. The present study aims to investigate the complication differences between elective tracheostomy and emergency-setting tracheostomy for patients with advanced hypopharyngeal squamous cell. The study group included 36 patients and analyzed the number and type of complications, functional outcomes and comparation of the laboratory testing in all the patients at 3 specific points (before tracheotomy, during the radiation therapy and at least 3 months after completion of radiation therapy). In addition, univariate analysis was performed in order to evaluate the prognosis of local control rates. The type and number of complications between elective and emergency-setting tracheostomy varied, but all the complications were resolved, and no hypoxic complications secondary to displacement of the tracheostomy tube or death cases related to the tracheostomy occurred. A total of 20/36 patients presented with complications, with 73% (16 patients) from the emergency tracheostomy cohort and 36% (4 patients) from the elective tracheostomy group. More than half of the elective tracheostomy (6/11 patients) responded favorably to the treatment, with a higher frequency than the patients with emergency tracheostomy (5/22 patients). The present study did not encounter significant statistical differences (P>0.05) of the treatment end-result regarding the type of tracheostomy performed, but the prediction analysis found for the patients aged under 60 years old, elective tracheostomy was associated with a higher chance of favorable treatment end result.

The Emergence of Tumor-Initiating Cells in an Advanced Hypopharyngeal Tumor Model Exhibits Enhanced Angiogenesis and Nuclear Factor Erythroid 2-Related Factor 2-Associated Antioxidant Effects.

Aims: Hypopharyngeal cancer (HPC) is associated with the worst prognosis of all head and neck cancers and is typically identified in an advanced stage at the time of diagnosis. While oxidative stress might contribute to the onset of HPC in patients using tobacco or alcohol, the extent of this influence and the characteristics of HPC cells in advanced stage remain to be investigated. In this study, we explored whether HPC cells survived from necrotic xenograft tumors at late stage would display increased tumor resistance along with altered tolerance to oxidative stress. Results: The remnant living HPC cells isolated from a late-stage xenograft tumor, named FaDu ex vivo cells, showed stronger chemo- and radioresistance, tumorigenesis, and invasiveness compared with parental FaDu cells. FaDu ex vivo cells also displayed increased angiogenic ability after re-transplantation in mice visualized by invivo near infrared-II fluorescence imaging modality. Moreover, FaDu ex vivo cells exhibited significant tumor-initiating cell (TIC)-related properties accompanied by a reduction of the level of reactive oxygen species, which was associated with the upregulation of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Interestingly, inhibition of Nrf2 by the RNA interference and the chemical inhibitor could reduce the TIC-related properties of FaDu ex vivo cells. Innovation: Oxidative stress potentially initiates HPC, but elevation of Nrf2-associated antioxidant mechanisms would be essential to mitigate this effect for promoting and sustaining the stemness of HPC at the advanced stage. Conclusion: Present data suggest that the antioxidant potency of advanced HPC would be a therapeutic target for the design of adjuvant treatment. Antioxid. Redox Signal. 41, 505-521.

Analysis of Th1/Th2 cytokine profile and clinical characteristics of patients with head and neck squamous cell carcinoma.

Immune system biomarkers in cancer pathogenesis offer new therapeutic avenues, as seen in cytokine (CK) profiles of laryngeal and hypopharyngeal tumors. A retrospective analysis was conducted on 58 patients with laryngeal and hypopharyngeal tumors and 27 patients with benign vocal cord lesions to explore the role of serum CKs in these diseases' characteristics and immunotherapy. The differences in the levels of 12 cytokines were measured. Additionally, the study examined the correlation between T helper cells (Th)1/Th2 cytokine levels and the clinical characteristics and immunotherapy efficacy of laryngeal and hypopharyngeal cancers. The results show that the balance of Th1/Th2 is biased towards Th2 in patients with laryngeal and hypopharyngeal tumors. Among these, interleukin (IL)-6 (P = 0.021) was highly expressed in laryngeal tumors, and the expression levels of IL-1β (P = 0.008), IL-6 (P = 0.005), and IL-8 (P = 0.05) were higher in patients with poorly differentiated laryngeal tumors. The level of IL-4 (P = 0.0048) was significantly correlated with tumor location. The expression levels of IL-2 (P = 0.010), IL-4 (P = 0.028), IL-10 (P = 0.011), IL-12p70 (P = 0.034), IL-17 (P = 0.024), tumor necrosis factor (TNF)-α (P = 0.003), and interferon (IFN)-γ (P = 0.007) were related to lymph node metastasis. The level of IFN-γ (P = 0.016) was correlated with the efficacy of neoadjuvant therapy, while the level of IFN-α (P = 0.013) was significantly correlated with programmed death ligand 1 (PD-L1) expression. The Principal Component Analysis (PCA) results showed that patients with tumors, poor differentiation, and lymph node metastasis had higher levels of Th1 and Th2 cytokine separation. In conclusion, the shift in the balance of Th1 and Th2 cytokine expression indicates higher tumor invasiveness, and IFN has potential as a circulating molecular marker for immunotherapy of head and neck squamous cell carcinoma.

Six-month mortality has decreased for patients with curative treatment intent for head and neck cancer in Sweden.

In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

Nutritional Status Among Head and Neck Cancer Patients, Tanzania

Background: Nutrition in cancer patients is a challenge as various mechanisms can lead to poor nutrition status, and this contributes to poor prognosis and quality of life. In developing countries, before one concludes that cancer is the culprit to malnutrition, one has to rule out access to food. The Head and Neck region is involved with the intake and initial processing of the food. Therefore, the presence of a tumor in any subsite directly affects nutritional status. Aim: This study aimed to establish nutritional adequacy among Head and Neck Cancer patients accessing services at a tertiary hospital in Tanzania. Method: The study was cross-sectional descriptive. Patients with head and neck cancer attended from 1st August 2022 to 31st January 2023 were recruited. Information about access to food was collected and nutrition was measured by anthropometric measurements and biochemical tests (serum albumin levels). After data collection, the correctness was checked by running frequency tables and analyzed by Statistical Package for the Social Sciences (SPSS) version 26. Results: The study involved a total of 113 participants aged from 15 to 93 years with a mean age of 51.81+/-17.439 years. There were 74 males and 39 females, making a ratio of 1.9:1. Most participants had laryngeal tumours (46%). 85.6% of patients had advanced disease, stage IV (52.2%).17% of patients had pre-existing dietary risk, and 36.3% had severe malnourishment at presentation. In this study,75% of patients with oropharyngeal tumours had malnutrition, followed by hypopharyngeal and nasopharyngeal tumours, each with 66.7%. Stage IV patients were severely malnourished (57.6%) which was statistically significant. Conclusion and recommendation: Laryngeal tumours are common in men and are related to advanced age. Most of the patients with Head and Neck Cancer (HNC) had severe malnourishment. Management of head and neck cancer should also address malnutrition which contributes to poor prognosis and quality of life.

Improved delineation with diffusion weighted imaging for laryngeal and hypopharyngeal tumors validated with pathology

ObjectiveThis study aims to determine the added value of a geometrically accurate diffusion-weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth. MethodsSixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumorHE) was delineated on the specimen reconstruction.Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTVMRI) and session two (GTVDW-MRI), as well as the clinical target volumes (CTVs), were compared to the tumorHE. ResultsThe mean tumorHE volume was 11.1 cm3, compared to a mean GTVMRI volume of 18.5 cm3 and a mean GTVDW-MRI volume of 15.7 cm3. The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61–0.99) for the GTVMRI and 0.91 (range: 0.53–1.00) for the GTVDW-MRI.The CTV volume also decreased when DWI was available, with a mean CTVMR of 47.1 cm3 and a mean CTVDW-MRI of 41.4 cm3. Complete tumor coverage was achieved in 15 and 14 tumors, respectively. ConclusionGTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage.

Citrus for wellness: Exploring the bioactive properties of Citrus medica fruit peel with emphasis on its anticancer, antioxidant, antimicrobial and anthelmintic properties

Citrus medica (Citron) is an underutilised plant consisting of various bioactive elements with numerous medicinal benefits. The present study aimed to evaluate the bioactive properties, including anthelmintic, antimicrobial, antioxidant and anticancer activities, of chloroform extract obtained from the of fruit peel of C. medica. The different types of phytochemicals present in the chloroform extract were analysed using GC-MS. The major components detected included n-hexadecanoic acid, octadecanoic acid, t-tetradecenal, 1-nonadecene etc. Anthelmintic study was conducted using Eisenia fetida as a test organism, revealing a significant anthelmintic effect in the C. medica fruit peel extract compared to the standard drug. Antimicrobial properties were assessed against five test bacterial and fungal strains. Antibacterial tests showed zones of inhibition ranging from 8 to 11 mm, while no prominent zones of inhibition were observed in antifungal tests. The DPPH assay demonstrated significant antioxidant properties of Citron fruit peel extract compared to the standard ascorbic acid. The Chloroform extract of citron fruit peel exhibited significant cytotoxic properties against FaDu (human hypopharyngeal tumour) cell line. The present study indicates the potential of the chloroform extract of C. medica fruit peel to be employed as an anthelmintic, antibacterial, antioxidant and anticancer agent. Hence, it emphasises the prominence that can be given to the dietary consumption of citrus fruit peel in various forms, such as dried peel, powder etc.

The Value of the Endoscope-Holding Arm in Transoral Pharyngeal Surgery.

Transoral pharyngeal surgery is mainly feasible with the use of a microscope or robotic systems. Data about alternative methods, with lower costs and easier availability, are sparse. We intended to examine to what extent the endoscope-holding arm is a suitable alternative to the microscope or robotic systems. We retrospectively reviewed subjects who underwent pharyngeal tumor resection with the endoscope-holding arm in our university department. We identified 13 subjects who underwent transoral pharyngeal surgery between November 2020 and November 2023. Most subjects presented with an oropharyngeal tumor (6/11 in the lateral wall or tonsil; 4/11 in the tongue base). The oropharyngeal lateral wall or tonsillar tumors were exposed with a standard mouth gag. The tongue-base tumors or hypopharyngeal tumors were exposed with an operating laryngoscope. Advantages over the microscope included an angled view. Advantages over robotic systems included haptic feedback and a faster setup. Advantages over both the microscope and robotic systems included lower costs and easier availability. Visualization with the endoscope was sufficient and similar to that of the microscope. Bimanual action was possible with surgical forceps and a monopolar electrode. Transoral pharyngeal surgery was feasible with the endoscope-holding arm. The endoscope-holding arm could be a cost-efficient alternative to the microscope or robotic systems.

Porphyrazine/phthalocyanine hybrid complexes – Antibacterial and anticancer photodynamic and sonodynamic activity

The activity of solitaire- and trans- zinc(II) porphyrazine/phthalocyanine hybrid complexes (1 and 2) as novel combinations for photodynamic and sonodynamic therapy were assessed against bacteria and cancer cells. In both manners, photostability, sonostability (1 MHz, 2 MHz, both 3 W) and singlet oxygen generation (with 1,3-diphenylisobenzofuran as a singlet oxygen chemical quencher) were measured. Hybrid complexes (1 and 2) were stable during irradiation and sonication. For photodynamic excitation manner the singlet oxygen quantum yields were calculated and were as follows 0.15 in DMF and 0.17 in DMSO for 1, and 0.1 in DMF and 0.18 in DMSO for 2. Sonodynamic manner revealed moderate generation of singlet oxygen by 2 upon 1 MHz, 3 W, while in 2 MHz, 3 W no generation was observed. Both hybrid complexes had high photodynamic antibacterial activity, reaching > 5 log reduction against both MRSA and Staphylococcus epidermidis, although their sonodynamic performance was negligible. Additionally, against squamous cell carcinoma (SCC-25) and hypopharyngeal tumor (FaDu) no photodynamic activity in vitro of 2 was observed, although the viability of reference MRC-5 fibroblasts was lowered. In sonodynamic manner 2 revealed slight activity against FaDu cells. Moreover, hybrid complex 2 revealed up to 38% inhibition of protease-activated protein C at 1 μM concentration, 52% inhibition of platelet-activated factor acetylhydrolase at 0.1 μM concentration and 29% inhibition at the concentration of 0.5 μM.

E-cadherin expression pattern in head and neck squamous cell carcinoma and its association with clinico-pathological predictors

BackgroundThe molecular makeup of a head and neck squamous cell carcinoma (HNSCC) could vary as per the geography and corresponding variability in prevalent etiopathological factors. The objective of this study was to analyze the expression pattern of E-cadherin (E-cad), a transmembrane glycoprotein with tumour suppressor function, in a cohort of HNSCC treated at a tertiary care medical centre in the southern part of India.Material and methodsAfter obtaining the institutional ethics committee’s permission, the expression of E-cad in HNSCC was assessed by using immunohistochemistry on retrospectively collected tumour specimens, obtained by a surgical cohort of cases operated between September 2018 and July 2019. The E-cad expression was then correlated with various clinical and pathological characteristics of HNSCC, retrieved via the medical records of corresponding patients.ResultsA total of 60 patients of HNSCC were included, most of whom had lesion in the oral cavity, in an advanced stage. The majority had a strong or moderate expression of E-cad on the surface. On analyzing further, oral cavity tumours had significantly less expression of E-cad compared to laryngeal and hypopharyngeal tumours taken together, and primary tumours had less E-cad expression than recurrent cases. Multivariate analysis with proportional odds regression showed the significant associations of low expression of E-cad expression with the moderate/poor differentiation of tumours and with the extranodal extension.ConclusionsAmong the HNSCC, the loss of E-cad expression was mostly associated with primary tumours of the oral cavity, moderate/poorly differentiated tumours, and in those HNSCCs that had an extranodal extension.

Hypopharyngeal cancer trends in a high-incidence region: A retrospective tertiary single center study.

Hypopharyngeal cancer has the bleakest prognosis among head and neck cancers due to its extensive submucosal involvement, advanced tumor stage, and limited surgical reconstruction options. Its primary causes include alcohol consumption, tobacco use, genetic predisposition, 1` diet, and socioeconomic conditions. While squamous cell carcinoma (SCC) accounts for 95% of hypopharyngeal tumors, it remains a rare form, comprising only 3%-5% of all SCC cases in the head and neck region. Globally, Central and Eastern Europe have the highest incidence rates for males (3.9 per 100000) and the third highest for females (2.26 per 100000), underscoring the significance of this seemingly uncommon condition. In Romania, hypopharyngeal cancer ranked 24th in incidence rate, with 634 new cases in 2020. To study the incidence, treatment and survival rates of hypopharyngeal tumor cases in a major ear, nose, throat (ENT) surgical center. A retrospective epidemiological clinical study was conducted on patients diagnosed and treated for hypopharyngeal cancer at the ENT department of "Carol Davila Central University Emergency Military Hospital" in Bucharest between January 2018 and August 2022. The study included 53 patients and was authorized by the Ethics Committee of Titu Maiorescu Doctoral School (Bucharest, Romania) and the Ethics Committee of Carol Davila Central University Emergency Military Hospital (Bucharest, Romania). Inclusion criteria required a positive histopathological diagnosis of hypopharyngeal cancer, tumor localization in the hypopharyngeal region, and informed consent for data usage. Exclusion criteria involved major psychiatric pathologies and disagreement for data usage. Diagnosis was based on ENT assessment, imaging reports, and laboratory data. Treatment methods were determined based on various factors. Additional tools, such as Adult Comorbidity Evaluation-27 and Karnofski Performance Status Scale, were used for risk assessment and functional capacity evaluation. Quality of life aspects were measured using the European Organisation for Reasearch and Treatment of Cancer Quality of Life Questionnaire Head and Neck-35 questionnaire. Our retrospective study examined 53 patients with hypopharyngeal cancer between January 2018 and August 2022. The majority of patients were male (94.3%), with an average age at diagnosis of 62.5 years. Among the patients, 20.75% were employed, 66.03% were retired, and 9.43% were unemployed. Smoking was prevalent among 69.81% of patients, while alcohol consumption was frequent in 32.07% of cases. The tumors were mostly diagnosed at an advanced stage (stage IV) and were predominantly SCC. Comorbidities were present in 83.01% of patients, with cardiovascular diseases being the most common. Dysphagia and neck mass were the most common symptoms reported. Treatment methods included surgery, radiation therapy, and chemotherapy. A favorable treatment response was observed in 22.64% of cases, while relapse occurred in 6 cases. Follow-up data was unavailable for some patients. In summary, our findings align with existing literature; however, we observed a higher severity.

Descriptive epidemiology of the head and neck cancers in old patients.

In Europe, as in other high-income (HI) countries, quite half of the newly diagnosed patients with head and neck (H and N) cancers are older than 65 years of age and their proportion within the prevalent cases is even higher. Moreover, the incidence rate (IR) for all H and N cancers sites increased with age and the survival rate is lower in older patients (≥65), compared with younger patients (<65). The number of older patients affected by H and N cancers will increase because of the increase in life expectancy. The aim of the article is to provide an epidemiological description of H and N cancers in the elderly population. Incidence and prevalence data by time periods and continents were extracted from the Global Cancer Observatory. The survival information for Europe is obtained from the EUROCARE and RARECAREnet projects. In 2020, according to the results from these data, slightly more than 900,000 cases have been diagnosed with H and N cancers in the world, and approximately 40% were older than 65 years of age. This percentage was higher, reaching approximately 50% in the HI countries. The highest number of cases was in the Asiatic populations, while the highest crude IR was in Europe and Oceania. Among H and N cancers occurring in the elderly, laryngeal and oral cavity cancers were the most common, while nasal cavities and nasopharyngeal cancers were the rarest. This was true for all the countries, excluding some Asiatic populations, in which tumour of the nasopharynx was more common. The five-year survival rate in the European population was low in the elderly, compared with the younger for all H and N cancers, and it ranged from approximately 60% for both salivary-gland type and laryngeal to 22% for hypopharyngeal tumors. For the elderly, the conditional 5-year survival after surviving one year became more than 60% for many H and N epithelial tumors. The high variability in the H and N cancer incidence around the world is due to the distribution of the major risk factors which for the elderly are mainly alcohol and smoking. The reasons for low survival in the elderly are most likely due to the complexity of treatment, the late arrival of patients at diagnosis, and the difficult access to specialized centers.

Pharyngocutaneous Fistula Following Total Laryngectomy: a High-Volume Tertiary Centre Series.

Pharyngocutaneous fistula is the leading complication following total laryngectomy. It delays complementary treatments, speech rehabilitation and oral feeding. Despite evolving medical care, fistula incidence remains high. There is no consensus regarding risk factors for fistula development. A standard score for fistula prediction is lacking. Study population included all patients submitted to total laryngectomy (with or without pharyngectomy) due to laryngeal or hypopharyngeal tumours, occurring between January 1st, 2012, and December 31st, 2016. Patient demographics were recorded as well as disease and treatment variables. Statistical analysis was performed using the IBM SPSS Statistics 25®. A previously described predictive model for fistula occurrence was applied. A total of 212 patients were included, the vast majority with advanced local disease (97.5%). Only 10% were submitted to rescue surgery. Fistula incidence was 39.9%. Our rates of locally advanced tumours, with extensive hypopharyngeal involvement, were higher than in most series. Age, tumour location, diabetes, previous chemoradiotherapy, advanced local and regional disease, extensive pharyngectomy, flap reconstruction, manual suture and low post-operative albumin level were associated to fistula occurrence on univariate analysis. Only salvage surgery and advanced local disease remained significant on multivariate analysis. An adapted Cecatto score correlated with fistula occurrence but has not achieved statistical significance. Predictive models for fistula occurrence are lacking. Cecatto score showed promising results in our population but large multicentric studies are necessary for cut-off adjustments.

Epidemiological and Clinical Aspects of Pharyngolaryngeal Pathologies in ENT Health Care

<i>Goal: </i>The aim was to establish the epidemiological and clinical profile of patients diagnosed with pharyngo-laryngeal pathologies. <i>Methods</i>: This is a descriptive prospective study conducted in ENT heath care service over a period of one year. The present study was done in the ENT-HNS department of the Reference Health Center of Commune V of Bamako. We consulted and included all patients that were visiting for the first time for pharyngo-laryngeal pathology. In addition, former patients who came for a second or umpteenth consultation and those admitted to another department requesting an ENT opinion were not included. <i>Results: </i>The pharyngo-laryngeal pathologies represented 15.21% (658 patients) of the total heath examination done on 4326 patients. We identified 60% women and 40% men. The age group 0-10 years constituted 42.10% of the cases. The average age was 19 years, while the extremes were 12 days and 83 years. The reasons for consultation were as follow: odynophagia (47.42%), fever (42.71%), rhinorrhea (41.64%), nasal obstruction (25.84%), headache (18.84%), and a cough (12.92%). Angina accounted for 37.39%, nasopharyngitis 29.78%, pharyngitis 27.20%, phlegmon-peri-tonsillar 2.74%, adenoids and laryngitis each 0.76%, foreign bodies 0.61%, laryngomalacia 0.46%, hypopharyngeal tumors and laryngeal papillomatosis each accounted for 0.15% of diagnoses. <i>Conclusion: </i>Pharyngo-laryngeal pathologies are dominated by inflammatory and infectious pathologies.

Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of “BH3, Bcl-2, Bcl-xL, and Mcl-1”. The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Salvage vs. Primary Total Laryngectomy in Patients with Locally Advanced Laryngeal or Hypopharyngeal Carcinoma: Oncologic Outcomes and Their Predictive Factors

The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.

Single-cell discovery of the scene and potential immunotherapeutic target in hypopharyngeal tumor environment

Hypopharyngeal carcinoma is a cancer with the worst prognosis. We constructed the first single-cell transcriptome map for hypopharyngeal carcinoma and explored its underlying mechanisms. We systematically studied single-cell transcriptome data of 17,599 cells from hypopharyngeal carcinoma and paracancerous tissues. We identified categories of cells by dimensionality reduction and performed further subgroup analysis. Focusing on the potential mechanism in the cellular communication of hypopharyngeal carcinoma, we predicted ligand-receptor interactions and verified them via immunohistochemical and cellular experiments. In total, seven cell types were identified, including epithelial and myeloid cells. Subsequently, subgroup analysis showed significant tumor heterogeneity. Based on the pathological type of squamous cell carcinoma, we focused on intercellular communication between epithelial cells and various cells. We predicted the crosstalk and inferred the regulatory effect of cellular active ligands on the surface receptor of epithelial cells. From the top potential pairs, we focused on the BMPR2 receptor for further research, as it showed significantly higher expression in epithelial cancer tissue than in adjacent tissue. Further bioinformatics analysis, immunohistochemical staining, and cell experiments also confirmed its cancer-promoting effects. Overall, the single-cell perspective revealed complex crosstalk in hypopharyngeal cancer, in which BMPR2 promotes its proliferation and migration, providing a rationale for further study and treatment of this carcinoma.