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Case Reports in Oncology 2024Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre's syndrome is an infectious...
INTRODUCTION
Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre's syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre's syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma.
CASE PRESENTATION
A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy. Three months after HN-PIT, the patient developed fever and neck pain, which led to a diagnosis of Lemierre's syndrome. The patient was treated with antibiotics and anticoagulants for at least 1 month. The patient's general condition and inflammatory findings on blood sampling showed gradual improvement, and a follow-up cervicothoracic computed tomography imaging showed that the venous thrombus had been obscured and the patient was doing well.
CONCLUSION
HN-PIT is a high-risk procedure for the development of Lemierre's syndrome due to irradiation-induced mucositis, and anticipating the development of Lemierre's syndrome during HN-PIT is important.
PubMed: 38304554
DOI: 10.1159/000535597 -
Oncology Reports Mar 2024Head and neck squamous cell carcinoma (HNSCC) is the seventh most commonly diagnosed cancer globally. HNSCC develops from the mucosa of the oral cavity, pharynx and...
Head and neck squamous cell carcinoma (HNSCC) is the seventh most commonly diagnosed cancer globally. HNSCC develops from the mucosa of the oral cavity, pharynx and larynx. Methylation levels of septin 9 () and short stature homeobox 2 () genes in circulating cell‑free DNA (ccfDNA) are considered epigenetic biomarkers and have shown predictive value in preliminary reports in HNSCC. Liquid biopsy is a non‑invasive procedure that collects tumor‑derived molecules, including ccfDNA. In the present study, a droplet digital PCR (ddPCR)‑based assay was developed to detect DNA methylation levels of circulating and in the plasma of patients with HNSCC. The assay was first set up using commercial methylated and unmethylated DNA. The dynamic changes in the methylation levels of and were then quantified in 20 patients with HNSCC during follow‑up. The results highlighted: i) The ability of the ddPCR‑based assay to detect very low copies of methylated molecules; ii) the significant decrease in and methylation levels in the plasma of patients with HNSCC at the first time points of follow‑up with respect to T; iii) a different trend of longitudinally DNA methylation variations in small groups of stratified patients. The absolute and precise quantification of and methylation levels in HNSCC may be useful for studies with translational potential.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; DNA Methylation; Genes, Homeobox; Carcinoma, Squamous Cell; Homeodomain Proteins; Polymerase Chain Reaction; Cytoskeletal Proteins; Cell-Free Nucleic Acids; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 38299234
DOI: 10.3892/or.2024.8711 -
Infection and Immunity Mar 2024Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis,...
Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, is associated with esophageal, gastric, and pharyngeal cancers, while is linked to oral cancer. However, no study has investigated the mechanistic links between these species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by and in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, -infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with compared with . At the 24-h time point, the presence of led to reduced extracellular itaconate, while triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how and , two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection.IMPORTANCEThe surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome's influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. , a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to compared with the early colonizer as an important first step toward understanding the impact of distinct oral species on the host immune response, which is an understudied determinant of OSCC development and progression.
Topics: Humans; Streptococcus anginosus; Carcinoma, Squamous Cell; Mouth Neoplasms; Dental Caries; Streptococcus; Macrophages; Succinates
PubMed: 38289109
DOI: 10.1128/iai.00536-23 -
Asian Pacific Journal of Cancer... Jan 2024Squamous Cell Carcinoma (SCC) of the buccal mucosa and gingiva accounts for approximately 10% of oral and pharyngeal cancers diagnosed in the United States each year,...
BACKGROUND
Squamous Cell Carcinoma (SCC) of the buccal mucosa and gingiva accounts for approximately 10% of oral and pharyngeal cancers diagnosed in the United States each year, with a disproportionally higher incidence in individuals of South Asian descent. However, little has been documented regarding trends pertaining to overall survival. Thus, this research serves to identify predictors of survival and determine if overall survival (OS) differs for South Asians compared to other races once they develop non-metastatic buccal mucosa or gingiva squamous cell carcinoma.
METHODS
A population-based, cohort study of patients registered in the National Cancer Database® (NCDB) between the years 2004-2016 was performed. Kaplan-Meyer Survival Curves were executed to examine overall survival, while univariable (UVA) and multivariable analysis (MVA) was performed to determine the effect of multiple variables on OS.
RESULTS
South Asians had longer median OS at 88.7 months, compared to 58.6 months and 38.3 months for Caucasians and African Americans respectively (p<0.001). In UVA, race was highly significant, but when the cohort was selected to include only those who had undergone surgical resection, no statistically significant difference remained. On MVA, lack of surgery, older age, higher grade, higher T and N stage, use of chemotherapy, higher comorbidity scores were associated with worse OS, but race was not significant.
CONCLUSION
South Asians in the US with non-metastatic buccal mucosa or gingiva SCC have better OS compared to Caucasians or African Americans, likely due to younger age at diagnosis (median 59 vs. 71 and 62 years old) and more frequent surgical resection (75% vs. 72% and 64%). In MVA, South Asians have similar OS as Caucasians.
Topics: Humans; United States; Mouth Mucosa; Cohort Studies; Prognosis; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Retrospective Studies
PubMed: 38285790
DOI: 10.31557/APJCP.2024.25.1.241 -
Genes Jan 2024This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian...
This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Instrumental variables within ±100 kb of the gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95% 0.81~0.99, = 2.25 × 10; 95% 0.65~0.94, = 2.55 × 10). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95% 1.14~1.75, = 1.88 × 10; 95% 1.46~2.53, = 1.16 × 10; 95% 4.49~6.33, = 3.36 × 10; 95% 4.56~7.12, = 6.91 × 10), without heterogeneity or pleiotropy ( > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus ( > 0.05). Reverse MR helped mitigate reverse causation effects. The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.
Topics: Female; Humans; Proprotein Convertase 9; PCSK9 Inhibitors; Subtilisin; Mendelian Randomization Analysis; Proprotein Convertases; Breast Neoplasms; Lung Neoplasms; Pharyngeal Neoplasms; Carcinoma in Situ
PubMed: 38275613
DOI: 10.3390/genes15010132 -
Oncology Letters Mar 2024Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision...
Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. was associated with tumor differentiation in oral cavity cancer (P=0.039), was associated with nodal involvement in pharyngeal cancer (P=0.017) and was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, and , for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). hypermethylation differed across HNSCC anatomic subsites (P0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.
PubMed: 38268779
DOI: 10.3892/ol.2024.14223 -
Endoscopy Dec 2024
Topics: Humans; Endoscopic Mucosal Resection; Hypopharynx; Carcinoma
PubMed: 38262458
DOI: 10.1055/a-2233-3082 -
BMC Cancer Jan 2024Total laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative...
Prophylactic pectoralis major flap to compensate for increased risk of pharyngocutaneous fistula in laryngectomy patients with low skeletal muscle mass (PECTORALIS): study protocol for a randomized controlled trial.
BACKGROUND
Total laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative complications following TL is the development of a pharyngocutaneous fistula (PCF), characterized by a communication between the neopharynx and the skin. PCF can lead to extended hospital stays, delayed oral feeding, and compromised quality of life. The use of a myofascial pectoralis major flap (PMMF) as an onlay technique during pharyngeal closure has shown potential in reducing PCF rates in high risk patients for development of PCF such as patients undergoing TL after chemoradiation and low skeletal muscle mass (SMM). Its impact on various functional outcomes, such as shoulder and neck function, swallowing function, and voice quality, remains less explored. This study aims to investigate the effectiveness of PMMF in reducing PCF rates in patients with low SMM and its potential consequences on patient well-being.
METHODS
This multicenter study adopts a randomized clinical trial (RCT) design and is funded by the Dutch Cancer Society. Eligible patients for TL, aged ≥ 18 years, mentally competent, and proficient in Dutch, will be enrolled. One hundred and twenty eight patients with low SMM will be centrally randomized to receive TL with or without PMMF, while those without low SMM will undergo standard TL. Primary outcome measurement involves assessing PCF rates within 30 days post-TL. Secondary objectives include evaluating quality of life, shoulder and neck function, swallowing function, and voice quality using standardized questionnaires and functional tests. Data will be collected through electronic patient records.
DISCUSSION
This study's significance lies in its exploration of the potential benefits of using PMMF as an onlay technique during pharyngeal closure to reduce PCF rates in TL patients with low SMM. By assessing various functional outcomes, the study aims to provide a comprehensive understanding of the impact of PMMF deployment. The anticipated results will contribute valuable insights into optimizing surgical techniques to enhance patient outcomes and inform future treatment strategies for TL patients.
TRIAL REGISTRATION
NL8605, registered on 11-05-2020; International Clinical Trials Registry Platform (ICTRP).
Topics: Humans; Laryngectomy; Pectoralis Muscles; Laryngeal Neoplasms; Retrospective Studies; Cutaneous Fistula; Pharyngeal Diseases; Postoperative Complications; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38225572
DOI: 10.1186/s12885-023-11773-7 -
Frontiers in Oncology 2023Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis... (Review)
Review
Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as , which are probably responsible of chronic inflammation and modulation of tumor microenvironment. is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., and ) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.
PubMed: 38179168
DOI: 10.3389/fonc.2023.1273516