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BMC Genomics May 2024The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific...
BACKGROUND
The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx.
RESULTS
Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed.
CONCLUSIONS
Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.
Topics: Humans; Hypopharyngeal Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Transcriptome; Hypopharynx; Gene Expression Profiling; Male; Sequence Analysis, RNA
PubMed: 38760729
DOI: 10.1186/s12864-024-10321-2 -
Frontiers in Immunology 2024Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue...
INTRODUCTION
Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood.
METHODS
We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it.
RESULTS
We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC.
DISCUSSION
Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.
Topics: Humans; Hypopharyngeal Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Receptors, Antigen, T-Cell; Receptors, Antigen, B-Cell; Carcinogenesis; Sequence Analysis, RNA; Transcriptome; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Gene Expression Regulation, Neoplastic; Male
PubMed: 38720887
DOI: 10.3389/fimmu.2024.1310376 -
Cureus Apr 2024Dysphagia is a common symptom encountered in clinical practice, typically associated with a wide range of etiologies, including structural abnormalities, inflammatory...
Dysphagia is a common symptom encountered in clinical practice, typically associated with a wide range of etiologies, including structural abnormalities, inflammatory conditions, neoplasms, and neurological disorders. However, the combination of subcutaneous emphysema, vocal cord palsy, enlarged arytenoids, and pooling of saliva in a dysphagic patient represents a rare and intriguing presentation. A 33-year-old female presented at a tertiary care hospital in Western India with hoarseness of voice, difficulty in swallowing, productive cough, and neck pain for two months with an abrupt increase in the severity of all symptoms in two days. A history of chewable tobacco use for six years was disclosed. Clinical evaluation revealed a thin build with platynychia and conjunctival pallor, dental staining, drooling of saliva, the presence of extensive subcutaneous emphysema on palpation of the neck, and absent laryngeal crepitus. Endoscopic evaluation was suggestive of right vocal cord palsy and enlarged, congested arytenoid cartilages, post-cricoid growth with pooling of saliva in bilateral pyriform fossae. A CT scan of the neck showed a 2x3 cm neoplastic growth in the hypopharynx, with subcutaneous emphysema and free air foci in the head and neck region, prompting an immediate tracheostomy and biopsy of the hypopharyngeal growth with Ryle's tube insertion. Squamous cell carcinoma was confirmed on the biopsy report. Due to its rarity, the possible underlying cause of idiopathic subcutaneous emphysema should be sought whenever encountered in clinical practice since these patients are potentially misdiagnosed. A high index of suspicion among clinicians, along with a consideration of the constellation of other symptoms and clinical features of a possible underlying hypopharyngeal cancer whenever encountering such patients is of key importance for prompting further investigations and treatment.
PubMed: 38711727
DOI: 10.7759/cureus.57727 -
Cureus Mar 2024With oropharyngeal cancer incidence rising globally, largely due to human papillomavirus (HPV), and hypopharyngeal cancer known for poor outcomes, innovative treatments... (Review)
Review
With oropharyngeal cancer incidence rising globally, largely due to human papillomavirus (HPV), and hypopharyngeal cancer known for poor outcomes, innovative treatments are needed. Transoral robotic surgery (TORS) offers a minimally invasive approach that may improve upon traditional open surgery and radiotherapy/chemoradiotherapy (RT/CRT) methods. We conducted a literature review and included 40 PubMed studies comparing TORS, open surgery, and RT/CRT for oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC), focusing on survival rates and swallowing function outcomes. TORS provides favorable survival outcomes and typically results in superior swallowing function post-treatment compared to other therapeutic modalities in both oropharyngeal and hypopharyngeal SCCs. The clinical benefits of TORS, including improved operative precision and minimized tissue disruption, along with the elimination of surgical incision recovery and reduced RT toxicity, suggest it is a valuable surgical approach for head and neck cancers.
PubMed: 38681419
DOI: 10.7759/cureus.57186 -
PloS One 2024In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for...
BACKGROUND
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.
MATERIAL AND METHOD
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.
RESULTS
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).
CONCLUSIONS
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.
Topics: Female; Humans; Male; Sweden; Hypopharyngeal Neoplasms; Intention; Head and Neck Neoplasms; Oropharyngeal Neoplasms
PubMed: 38625920
DOI: 10.1371/journal.pone.0296534 -
Cancer Control : Journal of the Moffitt... 2024Identify predictors of overall survival (OS) after hypopharyngeal/laryngeal cancer in Florida.
OBJECTIVE
Identify predictors of overall survival (OS) after hypopharyngeal/laryngeal cancer in Florida.
MATERIAL AND METHODS
We conducted a retrospective cohort study using data from the Florida Cancer Data System (FCDS) on patients diagnosed with hypopharyngeal or laryngeal cancer from 2010-2017. Primary outcome was OS. Hazard ratios (HRs) were estimated from univariable and multivariable Cox regression models for OS. Data was analyzed from November 1, 2022, to June 30, 2023.
RESULTS
We analyzed 6771 patients, who were primarily male (81.2%), White non-Hispanic (WNH) (78.2%), publicly insured (70.1%), married (51.8%), and residents of urban counties (73.6%). Black patients were more likely to be younger at diagnosis (38.9%), single (43.4%), to have distant SEER stage disease (25.6%). Median OS were lowest among patients who were uninsured (34 months), with hypopharyngeal site disease (18 months), and a smoking history (current: 34 months, former: 46 months, no smoking: 63 months). Multivariable Cox regression analysis showed worse OS for single/unmarried vs married (HR 1.47 [95%CI: 1.36-1.59], < .001), history of tobacco use (current: HR 1.62 [95%CI: 1.440-1.817], < .001; former smokers: (HR 1.28 [95%CI: 1.139-1.437], < .001) vs no history). Improved OS was observed among White Hispanics (WH) vs WNH (HR .73 [95%CI: .655-.817], < .001) and women vs men (HR .88 [95%CI: .807-.954], = .002). Geographical mapping showed that mortality rates were highest in census tracts with low income and education.
CONCLUSION
Our findings suggest that sociodemographic and clinical factors impact OS from hypopharyngeal/laryngeal cancer in Florida and vary geographically within the state. These results will help guide future public health interventions.
Topics: Humans; Male; Female; Florida; Laryngeal Neoplasms; Retrospective Studies; Ethnicity; Proportional Hazards Models
PubMed: 38623948
DOI: 10.1177/10732748241246958 -
Scientific Reports Apr 2024Prognostic factors for overall survival (OS), percutaneous endoscopic gastrostomy (PEG) dependency, and long-term speech rehabilitation via voice prosthesis (VP) after...
Prognostic factors for overall survival (OS), percutaneous endoscopic gastrostomy (PEG) dependency, and long-term speech rehabilitation via voice prosthesis (VP) after laryngectomy for laryngeal or hypopharyngeal cancer were investigated in a retrospective population-based study in Thuringia, Germany. A total of 617 patients (68.7% larynx; hypopharynx; 31.3%; 93.7% men; median age 62 years; 66.0% stage IV) from 2001 to 2020 were included. Kaplan-Meier and Cox multivariable regression analyses were performed. 23.7% of patients received a PEG. 74.7% received a VP. Median OS was 131 months. Independent factors for lower OS were stage IV (compared to stage II; hazard ratio [HR] = 3.455; confidence interval [CI] 1.395-8.556) and laryngectomy for a recurrent disease (HR = 1.550; CI 1.078-2.228). Median time to PEG removal was 7 months. Prior partial surgery before laryngectomy showed a tendency for independent association for later PEG removal (HR = 1.959; CI 0.921-4.167). Postoperative aspiration needing treatment was an independent risk factor (HR = 2.679; CI 1.001-7.167) for later definitive VP removal. Laryngectomy continuously plays an important role in a curative daily routine treatment setting of advanced laryngeal or hypopharyngeal cancer in Germany. Long-term dependency on nutrition via PEG is an important issue, whereas use of VP is a stable long-term measure for voice rehabilitation.
Topics: Male; Humans; Middle Aged; Female; Laryngectomy; Retrospective Studies; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Larynx; Treatment Outcome
PubMed: 38565603
DOI: 10.1038/s41598-024-58423-x -
Journal of Cancer Research and... Jan 2024Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of...
Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of patients with HCC and indicates a dismal prognosis. The head and neck region is an extremely uncommon site of metastatic HCC. Extrahepatic metastasis at first presentation, although uncommon, indicates advanced disease with a poor prognosis. Herein, we present the case of a 68-year-old male patient with a neck mass. Clinical examination and initial radiology were suggestive of an advanced primary pharyngeal malignancy. Biopsy showed neoplasm with large polygonal cells with clear/granular cytoplasm. The neoplastic cells showed positivity for Hep Par1, CD10, and CEA. A diagnosis of metastatic HCC was given. Subsequently, serum alpha-fetoprotein level was found to be markedly elevated and further imaging showed multiple mass lesions in the liver. It is necessary to recognize that the pharyngeal region is a potential site of HCC metastasis. Accurate diagnosis and risk stratification can help in avoiding unnecessary costs and delay in treatment.
Topics: Male; Humans; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Hypopharyngeal Neoplasms; Pharyngeal Neoplasms
PubMed: 38554358
DOI: 10.4103/jcrt.jcrt_1655_22 -
British Journal of Cancer Jun 2024Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations...
BACKGROUND
Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.
METHODS
Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.
RESULTS
Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.
CONCLUSIONS
DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.
Topics: Humans; Hypopharyngeal Neoplasms; Saliva; DNA Methylation; Male; Female; Middle Aged; Aged; DCC Receptor; Biomarkers, Tumor; Promoter Regions, Genetic; Genes, DCC; Case-Control Studies; Early Detection of Cancer; Receptor, Endothelin B; ROC Curve
PubMed: 38538728
DOI: 10.1038/s41416-024-02654-2 -
Frontiers in Immunology 2024To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced...
PURPOSE
To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC).
METHODS
We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed.
RESULTS
A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved.
CONCLUSION
The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.
Topics: Humans; Neoadjuvant Therapy; Immune Checkpoint Inhibitors; Treatment Outcome; Hypopharyngeal Neoplasms; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Staging
PubMed: 38524124
DOI: 10.3389/fimmu.2024.1364799