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The Laryngoscope May 2023Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to... (Review)
Review
OBJECTIVE
Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes.
METHODS
We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA).
RESULTS
The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither.
CONCLUSION
We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery.
LEVEL OF EVIDENCE
4 Laryngoscope, 133:1138-1145, 2023.
Topics: Humans; Hypopharyngeal Neoplasms; Hypopharynx; Laryngeal Neoplasms; Organ Preservation; Neoplasm Staging; Carcinoma, Squamous Cell; Larynx
PubMed: 35801573
DOI: 10.1002/lary.30279 -
International Journal of Oncology Apr 2022Squamous cell carcinoma is the major form of malignancy that arises in head and neck cancer. The modest improvement in the 5‑year survival rate underpins its complex...
Squamous cell carcinoma is the major form of malignancy that arises in head and neck cancer. The modest improvement in the 5‑year survival rate underpins its complex etiology and provides the impetus for the discovery of new therapeutics. The present study describes the discovery of an indole‑based small molecule (24a) that was a potent cytotoxic agent with antiproliferative and pro‑apoptotic properties against a pharyngeal carcinoma cell line, Detroit 562, effectively killing the cells at a half‑maximal inhibitory concentration of 0.03 µM, as demonstrated using cell proliferation studies. The antiproliferative property of 24a was demonstrated by its ability to promote G/M blockade, as assessed by cell cycle analysis using flow cytometry and the monitoring of real‑time cell cycle progression by the fluorescence ubiquitination‑based cell cycle indicator. This pro‑apoptotic property is supported by the promotion of TUNEL‑staining and increase in the activities of caspases‑3/7 and ‑6, in addition to the expression of death receptors and the cleavage of poly (ADP‑ribose) polymerase 1 protein as demonstrated by western blotting. Given that Detroit 562 lacks functional p53, it is suggested that 24a acts independently of the tumor suppressor.
Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cytotoxins; Growth Inhibitors; Humans; M Phase Cell Cycle Checkpoints; Pharyngeal Neoplasms
PubMed: 35211767
DOI: 10.3892/ijo.2022.5331 -
Plastic and Reconstructive Surgery Oct 2023There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue...
BACKGROUND:
There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction.
METHODS:
This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence.
RESULTS:
Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15.
CONCLUSION:
The authors’ risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction.
CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
PubMed: 37768217
DOI: 10.1097/PRS.0000000000010661 -
Viruses May 2022An aetiological role of human papillomavirus (HPV) and/or human polyomaviruses (HPyVs) has been proposed in adenoid cystic carcinoma (AdCC). Moreover, HPV-related...
Analysis of Human Papillomavirus (HPV) and Polyomaviruses (HPyVs) in Adenoid Cystic Carcinoma (AdCC) of the Head and Neck Region Reveals Three HPV-Positive Cases with Adenoid Cystic-like Features.
An aetiological role of human papillomavirus (HPV) and/or human polyomaviruses (HPyVs) has been proposed in adenoid cystic carcinoma (AdCC). Moreover, HPV-related multiphenotypic carcinoma (HMSC) was recently introduced as an emerging entity of the sinonasal region. Here, we primarily want to study the role of HPV/HPyV in a large AdCC cohort and, secondly, possibly identify and characterize HMSC. Tumour DNA from 68 patients initially diagnosed with AdCC between 2000 and 2012 was, therefore, tested for 27 HPV types and 10 HPyVs. HPV DNA-positive samples were micromorphologically re-evaluated, further stained for p16, S100, p63 and CD117 and tested for the presence of the MYB-NFIB fusion transcript. Notably, no samples were HPyV-positive, while one sinonasal and two tonsillar carcinomas were HPV- and p16-positive. After re-evaluating the micromorphology, immunohistochemistry and presence of fusion transcripts, all tumours had the same appearance and fitted within the diagnosis of HMSC, but in all these three cases, the morphology of the HMSC and basaloid squamous cell carcinoma was overlapping. We conclude that HPV and HPyV have no major role in AdCC. However, based on our data, we also suggest that HMSC should be considered as a basaloid variant of squamous cell carcinoma, and not its own entity, until better characterized.
Topics: Adenoids; Alphapapillomavirus; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Humans; Papillomaviridae; Papillomavirus Infections; Paranasal Sinus Neoplasms; Polyomavirus
PubMed: 35632780
DOI: 10.3390/v14051040 -
Head & Neck Nov 2021To investigate a novel velopharyngeal squeeze maneuver (VPSM) and novel endoscopic pharyngeal contraction grade (EPCG) scale for the evaluation of pharyngeal motor...
Assessment of pharyngeal motor function using a novel velopharyngeal squeeze maneuver and a novel endoscopic pharyngeal contraction grade scale in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.
BACKGROUND
To investigate a novel velopharyngeal squeeze maneuver (VPSM) and novel endoscopic pharyngeal contraction grade (EPCG) scale for the evaluation of pharyngeal motor function.
METHODS
During endoscopic examination of 77 post-irradiated nasopharyngeal carcinoma patients and control subjects, VPSM was rated and lateral pharyngeal wall movement graded with EPCG scale during swallowing. Pharyngeal constriction ratio (PCR) measured by videofluoroscopy was used for correlation.
RESULTS
VPSM and EPCG scale showed almost perfect intra-rater and inter-rater reliability (Kappa: >0.90). VPSM was present in 61% of patients suggesting good pharyngeal motor function. VPSM was predictive of EPCG scale (Wald statistic = 29.99, p < 0.001). EPCG scale also correlated strongly with PCR (r: 0.812) and was predictive for aspiration (odds ratio: 22.14 [95% CI 5.01-97.89, p < 0.001]).
CONCLUSIONS
VPSM and EPCG scale are two novel tools to assess pharyngeal motor function, and both correlate well with pharyngeal contractility and aspiration.
Topics: Deglutition; Deglutition Disorders; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Pharynx; Reproducibility of Results
PubMed: 34523766
DOI: 10.1002/hed.26871 -
Frontiers in Cell and Developmental... 2022Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell...
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell carcinoma (LSCC) and oral squamous cell carcinoma are common HNSCC subtypes. Patients with metastatic HNSCC have a poor prognosis. Therefore, identifying molecular markers for the development and progression of HNSCC is essential for improving early diagnosis and predicting patient outcomes. Gene expression RNA-Seq data and patient clinical traits were obtained from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) and Gene Expression Omnibus databases. Differentially expressed gene (DEG) screening was performed using the TCGA-HNSC dataset. Intersection analysis between the DEGs and a list of core matrisome genes obtained from the Matrisome Project was used to identify differentially expressed matrisome genes. A prognostic model was established using univariate and multivariate Cox regression analyses, least absolute shrinkage, and selection operator (LASSO) regression analysis. Immune landscape analysis was performed based on the single-sample gene set enrichment analysis algorithm, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, prognostic value, receiver operating characteristic curve analysis, and gene mutation analyses. Immunohistochemical results regarding prognostic protein levels were obtained from the Human Protein Atlas. Single-gene RNA-sequencing data were obtained from GSE150321 and GSE172577 datasets. CCK-8 and Transwell assays were used to confirm cell proliferation and migration. A total of 1,779 DEGs, including 939 upregulated and 840 downregulated genes, between tumor and normal samples were identified using the TCGA-HNSC microarray data. Intersection analysis revealed 52 differentially expressed matrisome-related genes. After performing univariate and multivariate Cox regression and LASSO analyses, a novel prognostic model based on six matrisome genes (, , , , , and ) for HNSCC was established. This risk model can successfully predict HNSCC survival. The high-risk group had worse prognoses and higher enrichment of pathways related to cancer development than the low-risk group. Silencing in HNSCC cell lines promoted cell proliferation and migration. This study provides a novel prognostic model for HNSCC. Thus, , , , , , and may be the promising biomarkers for clinical practice.
PubMed: 36081907
DOI: 10.3389/fcell.2022.884590 -
Frontiers in Oncology 2021Recent advances made in treatment for head and neck squamous cell carcinoma (HNSCC) highlight the need for new prediction tools to guide therapeutic strategies. In this...
Recent advances made in treatment for head and neck squamous cell carcinoma (HNSCC) highlight the need for new prediction tools to guide therapeutic strategies. In this study, we aimed to develop a HNSCC-targeting multiplex immunohistochemical (IHC) panel that can evaluate prognostic factors and the intratumor heterogeneity of HNSCC. To identify IHC-based tissue biomarkers that constitute new multiplex IHC panel, a systematic review and meta-analysis were performed to analyze reported IHC biomarkers in laryngeal and pharyngeal SCC in the period of 2008-2018. The Cancer Genome Atlas (TCGA) and Reactome pathway databases were used to validate the prognostic and functional significance of the identified biomarkers. A 14-marker chromogenic multiplex IHC panel including identified biomarkers was used to analyze untreated HNSCC tissue. Forty-five high-quality studies and thirty-one candidate tissue biomarkers were identified (N = 7062). Prognostic validation in TCGA laryngeal and pharyngeal SCC cohort (N = 205) showed that β-catenin, DKK1, PINCH1, ADAM10, and TIMP1 were significantly associated with poor prognosis, which were related to functional categories such as immune system, cellular response, cell cycle, and developmental systems. Selected biomarkers were assembled to build a 14-marker panel, evaluating heterogeneity and polarized expression of tumor biomarkers in the tissue structures, which was particularly related to activation of Wnt/β-catenin pathway. Integrated IHC analysis based on a systemic review and meta-analysis provides an proteomics tool to assess the aggressiveness and intratumor heterogeneity of HNSCC.
PubMed: 34490110
DOI: 10.3389/fonc.2021.713561 -
PloS One 2023Squamous papillomas (SPs) of the head and neck are usually benign lesions associated with human papilloma virus (HPV) infection. However, the reported HPV detection...
Squamous papillomas (SPs) of the head and neck are usually benign lesions associated with human papilloma virus (HPV) infection. However, the reported HPV detection rates vary widely, especially with respect to anatomical distribution. The etiology of SPs in the head and neck remains unclear; analyzing HPV genotypes of SPs based on anatomical sites could assist in clarifying the pathogenesis of SPs in the head and neck. Therefore, the aim of this study was to review the prevalence, subtypes, and anatomical distribution of HPV in head and neck SPs at a hospital in China; we also investigated whether p16, a marker of HPV infection in oropharyngeal carcinoma, could serve as a surrogate marker for HPV in head and neck SPs. The presence of HPV DNA of 23 types (5 low-risk HPV and 18 high-risk HPV types) was detected via real-time PCR. p16 immunohistochemistry was performed using SP sections. Age, sex, anatomical location, and HPV subtype were recorded for each case. In total, 105 SPs were identified, including 47 in the larynx, 42 in the pharynx, 6 in the external auditory canal (EAC), 5 in the oral cavity, and 5 in the nasal cavity. HPV was found in 57 (54.3%) cases, with the highest positivity rate in the larynx (46/47; 97.9%). Only 5/42 (11.9%) patients showed HPV positivity in the pharynx. HPV incidence was highly dependent on the anatomical site. SPs in the larynx and EAC were more likely to carry HPV than those in other anatomical sites. High-risk HPV infections were rarely associated with SPs in the head and neck region. The sensitivity and specificity of p16 immunohistochemistry for HPV infection were 88% and 96%, respectively. There may be an association between p16 and HPV infection in head and neck SPs, but further studies are needed to validate this assertion.
Topics: Humans; Head and Neck Neoplasms; Papillomavirus Infections; Papilloma; Mouth; Carcinoma, Squamous Cell; Genotype; Cyclin-Dependent Kinase Inhibitor p16; Papillomaviridae; DNA, Viral
PubMed: 37566623
DOI: 10.1371/journal.pone.0290004 -
Ear, Nose, & Throat Journal 2019Necrotizing sialometaplasia (NSM) is a benign, reactive metaplastic condition of the minor salivary gland tissue typically seen in the setting of injury, chemical or...
Necrotizing sialometaplasia (NSM) is a benign, reactive metaplastic condition of the minor salivary gland tissue typically seen in the setting of injury, chemical or traumatic, and is nonneoplastic and self-limited. The diagnosis may be challenging as it may clinically mimic malignancy. We present the case of a 74-year-old male with a 1 pack per day smoking history for 60 years who presented with a reported 20-pound weight loss, dysphagia, and dysphonia progressing over the course of 6 months and found to have a 3.5-cm hypopharyngeal mass on computed tomography imaging and fiberoptic laryngoscopy. Initial frozen section of the mass was concerning for squamous cell carcinoma in situ, but permanent specimens returned as nondiagnostic. Repeat biopsy established a diagnosis of NSM. Two-month follow-up showed complete resolution of the mass. Clinicians should be aware that NSM may present in unusual locations when considering differential diagnoses for laryngeal masses and evaluating for malignancy.
Topics: Aged; Humans; Hypopharynx; Male; Pharyngeal Diseases; Sialometaplasia, Necrotizing
PubMed: 30966809
DOI: 10.1177/0145561319840826 -
Acta Medica Okayama Dec 2021The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify...
Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas.
The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Free Tissue Flaps; Humans; Male; Middle Aged; Neoplasms, Second Primary; Pharynx; Plastic Surgery Procedures; Retrospective Studies; Young Adult
PubMed: 34955541
DOI: 10.18926/AMO/62813