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Computational Intelligence and... 2022Hypopharyngeal carcinoma is usually present at late stages, necessitating an aggressive line of management consisting of surgical procedures, chemotherapy, and radiation... (Review)
Review
Hypopharyngeal carcinoma is usually present at late stages, necessitating an aggressive line of management consisting of surgical procedures, chemotherapy, and radiation therapy, depending on the case. Practitioners tend to support total laryngectomies or total esophagostomies for most cases of hypopharyngeal carcinoma. The extensive procedures needed will most probably require, depending on the residual defect, a follow-up reconstructive procedure that might require utilizing flaps. Types of reconstructive methods and types of grafts or flaps used could be divided into a multitude of categories depending on the magnitude, shape, extension, and whether the underlying defect that is being reconstructed is circumferential or not. These reconstructive procedures are aimed at improving the quality of life, improving the aesthetic outcome, and restoring the functionality of the pharyngoesophageal segment. When it comes to hypopharyngeal cancer, the most common kind is squamous cell carcinoma (SCC), which has the worst prognosis of all the head and neck malignancies. Overall, the 5-year survival rate remains low, despite recent advancements in diagnostic imaging, radiation, and chemotherapy, as well as enhanced surgical methods and techniques. Hypopharyngeal malignancies are more probable than other tumors to present with advanced primary illness, with nodal metastasis a distinct possibility. The size and amount of local dissemination of the original carcinoma, as well as the extent of involvement of regional lymph nodes, are the most critical factors in predicting prognosis. Hypopharyngeal cancers are more likely than other head and neck cancers to manifest with distant metastases at the time of diagnosis. The appearance of second primary tumors, as well as the development of distant metastases, is a contributing factor to poor survival rate. Imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) with contrast remain the gold standard for evaluating hypopharyngeal carcinoma in the early stages. In most cases, imaging leads to an increase in the tumor stage at the time of presentation. . The main objectives are to review the research published about flaps, outline the optimum situations that will dictate the usage of a few of the most often used flaps for the rebuilding of the hypopharyngeal segment defects, and outline some of the complications associated with reconstruction. . The processing was carried out with the title-specific search of the PubMed database using the query terms "hypopharyngeal carcinoma" and "reconstruction" to identify the most relevant articles without restricting publication dates. Information about the types of defects and methods of reconstruction was extracted from the reviewed articles. Two books were also reviewed, which were Regional and Free Flaps for Head and Neck Reconstruction (second edition) and Head and Neck Reconstruction: A Defect-Oriented Approach. . Deciding the appropriate approach to a case should be individualized and should depend on the capabilities of the center, the defect's size and status, and lastly, the surgeon's training. The use of interpretation in the diagnosis of flaps can offer the best results in restoring functionality and vascularity and might also offer improved cosmesis.
Topics: Carcinoma, Squamous Cell; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Laryngectomy; Quality of Life; Retrospective Studies
PubMed: 35178078
DOI: 10.1155/2022/6132481 -
International Journal of Molecular... May 2022Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those...
Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.
Topics: Biomarkers, Tumor; Head and Neck Neoplasms; Histone Demethylases; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Neoplasm Recurrence, Local; Prognosis; Snail Family Transcription Factors; Squamous Cell Carcinoma of Head and Neck
PubMed: 35563463
DOI: 10.3390/ijms23095075 -
The Oncologist Jul 2021The Japanese Ministry of Health, Labour and Welfare approved a drug called borofalan ( B), a treatment system, and a dose calculation program for boron neutron capture... (Review)
Review
The Japanese Ministry of Health, Labour and Welfare approved a drug called borofalan ( B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) in March 2020. The application pertaining to the products submitted to the Pharmaceuticals and Medical Devices Agency was supported by a Japanese, open-label, uncontrolled trial (Study 002) in patients with unresectable, locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiotherapy, or in those with unresectable locally advanced or locally recurrent (LA/LR) head and neck nonsquamous cell carcinoma. The drug was administered as a single intravenous dose using infusion rates of 200 mg/kg per hour for the first 2 hours after the start of administration and 100 mg/kg per hour during irradiation. Neutron irradiation was performed using the devices at a single dose of 12 Gy-equivalent for oral, pharyngeal, or laryngeal mucosa for up to 60 minutes from 2 hours after the start of drug administration. The primary endpoint was the overall response rate (ORR). The results of Study 002 showed that the ORR based on an assessment of the Independent Central Review Committee per RECIST version 1.1 was 71.4% (90% confidence interval [CI], 51.3%-86.8%). The lower limit of the 90% CI exceeded the prespecified threshold for ORR. When BNCT is applied to patients with unresectable LA/LR head and neck cancer, precautions should be taken, and patients should be monitored for possible onset of dysphagia, brain abscess, skin disorder, crystal urine, cataract, and/or carotid hemorrhage. IMPLICATIONS FOR PRACTICE: Borofalan ( B), a treatment system and a dose calculation program for boron neutron capture therapy (BNCT), demonstrated significant efficacy in an open-label, uncontrolled trial in which overall response rate was the primary endpoint for patients with unresectable locally advanced or locally recurrent head and neck cancer. Although no information about survival benefits was obtained, BNCT will become an effective treatment option that is expected to manage local lesions that are intractable with any standard therapy. In addition, BNCT is expected to maintain quality of life of the intended patient population, on account of its high tumor selectivity and low invasiveness.
Topics: Boron Neutron Capture Therapy; Head and Neck Neoplasms; Humans; Neoplasm Recurrence, Local; Quality of Life; Squamous Cell Carcinoma of Head and Neck
PubMed: 33928712
DOI: 10.1002/onco.13805 -
Indian Journal of Otolaryngology and... Oct 2022Laryngeal cancer treatment is often wrought with challenges, pharyngocutaneous fistula formation (PCF) in patients undergoing either primary or salvage laryngectomy for...
Laryngeal cancer treatment is often wrought with challenges, pharyngocutaneous fistula formation (PCF) in patients undergoing either primary or salvage laryngectomy for laryngeal and hypopharyngeal for squamous cell carcinoma is an important one. We aimed to study the factors before and at the surgery that are associated with PCF formation in a South Indian tertiary care hospital. A retrospective chart review of 127 patients who underwent total laryngectomy (TL) between May 2014 and April 2019 at our centre were done. Data was collected, including patient age and gender, comorbidities (Diabetes mellitus, COPD and hypothyroidism), smoking, tumor stage and site, prior tracheostomy, prior radiation, concurrent neck dissection and type of pharyngoplasty, Preoperative hemoglobin and albumin levels, surgical margin status and development of a PCF was also done. Further details specific to the development of a PCF were recorded for that subset of patients including the length of time to fistula, mode of closure, time of closure and modality of management. The overall incidence of PCF was 16.5% (21 of 127 patients), and the median time from TL to the diagnosis of PCF was 6 days (range, 3-20 days). The analysis was done separately for laryngectomies without any pharyngeal reconstruction (112/127 patients). In patients treated with a primary TL, the incidence of PCF was 12.20% (10 of 82) and 26.66% (8 of 30) after salvage TL. Subset analysis for type of pharyngoplasty repair showed 12% (15/127) underwent different types of vascularised/muscular flap for smaller residual pharyngeal mucosa, of which 20% (3/15) developed PCF and one patient developed haematoma needing exploration and re-suturing. The predictive factors for PCF were hypopharynx cancer (< 0.05), surgical margin positivity ( < 0.0001), female gender ( < 0.05), absence of prior tracheostomy (< 0.05) and tumor extension into pyriform sinus mucosa ( < 0.05). Preoperative patient factors of gender and site of primary along with histological margin positivity and extension of tumor to the pyriform sinus mucosa were significant risk factors for PCF formation. Pre-Op radiotherapy remains a strong clinical suspicion but not statistically significant.
PubMed: 36452720
DOI: 10.1007/s12070-020-02046-x -
Head & Neck Jan 2021We conducted the current systemic review to provide up-to-date literature summary and optimal evidence-based recommendations for ipsilateral radiation for squamous cell... (Review)
Review
BACKGROUND
We conducted the current systemic review to provide up-to-date literature summary and optimal evidence-based recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil.
METHODS
We performed literature search of peer-reviewed journals through PubMed. The search strategy and subject-specific keywords were developed based on the expert panel's consensus. Articles published from January 2000 to May 2020 with full text available on PubMed and restricted to the English language and human subjects were included. Several prespecified search terms were used to identify relevant publications and additional evidence published since the initial American College of Radiology Appropriateness Criteria Ipsilateral Tonsil Radiation recommendation was finalized in 2012. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
The initial search and review returned 46 citations. The authors added three citations from bibliographies, websites, or books not found in the literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, or focused on unknown primary disease. Several commonly encountered clinical case variants were created and panelists anonymously rated each treatment recommendation. The results were reviewed and disagreements discussed.
CONCLUSIONS
The panel provided updated evidence and recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil in the setting of primary radiation-based therapy and postoperative adjuvant radiotherapy. This committee did not reach agreements for some case variants due to a lack of strong evidence supporting specific treatment decisions, indicating a further need for research in these topics.
Topics: Carcinoma, Squamous Cell; Humans; Palatine Tonsil; Radiotherapy, Adjuvant; Radium; United States
PubMed: 33068064
DOI: 10.1002/hed.26492 -
The Korean Journal of Physiology &... Nov 2022The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu...
The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.
PubMed: 36302620
DOI: 10.4196/kjpp.2022.26.6.447 -
International Journal of Environmental... Aug 2021The main aim of this study was to test whether the use of mouthwash is associated with subtypes of squamous cell carcinoma of the head and neck (SCCHN) and to test the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The main aim of this study was to test whether the use of mouthwash is associated with subtypes of squamous cell carcinoma of the head and neck (SCCHN) and to test the potential risk of SCCHN depending on the mouthwash use duration, frequency, or alcoholic content.
MATERIALS AND METHODS
We performed a meta-analysis using Web of Science and Scopus databases to detect the risk change associated with mouthwash use depending on the alcohol content, duration and frequency of use, and anatomical location. We used a random-effects model with the Sidik-Jonkman estimator for effect size model measures.
RESULTS
We included 17 studies in the meta-analysis containing 17,085 cases and 20,032 controls. The risk difference for SCCHN between mouthwash users and non-users was minimal, with a value of -0.02 [-0.05, 0.01]. Alcoholic mouthwash use was associated with a minimal decrease in risk (of -0.01 [-0.07, 0.05]). Frequent usage of mouthwash was associated with a statistically significant risk increase for SCCHN but the risk increase was marginal (0.04, [0.01, 0.06]).
CONCLUSIONS
Overall, our study failed to show a statistically significant correlation between mouthwash use and the risk of SCCHN. The only statistically significant correlation that we could identify was between frequent usage and SCCHN, potentially caused by prolonged contact between some constituents of mouthwash (possibly alcohol) and the oral epithelium.
Topics: Carcinoma, Squamous Cell; Ethanol; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Mouthwashes; Neck
PubMed: 34360508
DOI: 10.3390/ijerph18158215 -
Annals of Translational Medicine May 2021Head and neck squamous cell carcinomas (HNSCC) arising from the oral cavity, pharynx, and larynx constitute the 6 most common human cancer. Human papillomavirus... (Review)
Review
Head and neck squamous cell carcinomas (HNSCC) arising from the oral cavity, pharynx, and larynx constitute the 6 most common human cancer. Human papillomavirus (HPV)-positive tumours are distinct from HPV-negative counterparts, with HPV status affording clear clinical utility, prognostic benefit and better treatment outcomes. In contrast to their HPV-positive counterparts, HPV-negative tumours are characterized by high mutational load and chromosomal aberrations, with varying copy number alteration (CNA) profiles. HNSCC are distinct tumours at the chromosomal, gene and expression levels, with additional insight gained from immune profiling. Based on mutational analyses, HNSCC are categorized as HPV-positive, HPV-negative CNA-silent, and HPV-negative CNA-high tumours. Furthermore, gene expression profiling segregates these tumours into atypical, classical, basal, and mesenchymal, with clear differences observed between tumours of the oral cavity, oropharynx, hypopharynx and larynx. Additional immune profiling further classifies tumours as either immune-active or immune-exhausted. The clinical utility and impact of these tumour molecular subtypes however remains to be determined. HNSCC harbor high levels of somatic mutations. They display loss at 3p and 18q and gain at 3q and 8q, with mutations in and . Important pathways include the p53 and RB pathways which are involved in cell cycle control and are frequently lost in HPV-negative tumours, the WNT-β-catenin pathway related to the mesenchymal subtype and smoking etiology, and the PI3K pathway which includes the most common genetic alteration in HPV-positive HNSCC. Understanding the mutational, genomic and transcriptomic landscape of HNSCC has leveraged better therapeutic approaches to manage this group of diseases, and it is hoped that additional insight into the molecular subtypes of HNSCC and its specific subsites will further drive improved strategies to stratify and treat patients with this debilitating disease.
PubMed: 34164549
DOI: 10.21037/atm-20-6264 -
European Review For Medical and... Apr 2023Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the...
OBJECTIVE
Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the cellular level of the mucosa and squamous cell carcinoma (SCC).
PATIENTS AND METHODS
A total of 60 CLE sequences recorded in 5 patients with SCC undergoing laryngectomy between October 2020 and February 2021 were analyzed. The corresponding histologic sample derived from H&E staining was assigned to each sequence, capturing CLE images of the tumor and healthy mucosa. In addition, the cellular structure analysis was performed to diagnose SCC by measuring the total number of cells and cell size in 60 sequences in a fixed field of view (FOV) with 240 μm in diameter (45,239 μm2).
RESULTS
Out of 3,600 images, 1,620 (45%) showed benign mucosa and 1,980 (55%) SCC. The automated analysis yielded a difference in cell size, with healthy epithelial cells being 171.9±82.0 μm2 smaller than SCC cells, which were 246.3±171.9 μm2 and showed greater variability in size (p=0.037). In addition, due to the probe's fixed FOV, there was a difference in cell count with a total of 188.7±38.3 and 124.8±38.6 cells in images of normal epithelium and SCC (p<0.001), respectively. Regarding cell density as a criterion for the differentiation of benign/malign, using a cut-off value of 145.5 cells/FOV, we obtained sensitivity and specificity of 88.0% and 71.9%, respectively.
CONCLUSIONS
SCC reveals marked differences at a cellular level compared to the healthy epithelium. Our results further support the importance of this feature for identifying SCC during CLE imaging.
Topics: Humans; Microscopy, Confocal; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cell Count; Lasers
PubMed: 37140313
DOI: 10.26355/eurrev_202304_32146 -
American Society of Clinical Oncology... Jan 2023Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, and larynx. Within the United...
Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, and larynx. Within the United States, head and neck cancer (HNC) accounts for 66,470 new cases, or 3% of all malignancies, annually. The incidence of HNC is rising, largely driven by increases in oropharyngeal cancer. Recent molecular and clinical advancements, particularly with regard to molecular and tumor biology, reflect the heterogeneity of the subsites contained within the head and neck. Despite this, existing guidelines for post-treatment surveillance remain broad without much consideration given to different anatomic subsites and etiologic factors (such as human papillomavirus [HPV] status or tobacco exposure). Surveillance incorporating the physical examination, imaging, and emerging molecular biomarkers is an essential part of care for patients treated for HNC and allows for the detection of locoregional recurrence, distant metastases, and second primary malignancies aiming for better functional and survival outcomes. Additionally, it allows for evaluation and management of post-treatment complications.
Topics: Humans; Carcinoma, Squamous Cell; Papillomavirus Infections; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Oropharyngeal Neoplasms
PubMed: 37079869
DOI: 10.1200/EDBK_389718