Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

Fibroblast activation protein (FAP) as a prognostic biomarker in multiple tumors and its therapeutic potential in head and neck squamous cell carcinoma

Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.

ANALYSIS OF 26,826 PATIENTS WITH TUMORS IN THE HEAD AND NECK

A series of 26,826 patients with head and neck tumer as confirmed by pathology from January 1970 to December 1989 are analyzed. It accounted for 39. 5% of all the tumors blopsied in the same interval. In this series, 72. 4% was malignant which accounted for 45. 77% of malignant tumors in different parts of the whole body. For benign tumors in the head and neck, the ratio of male to female was 0. 84:1, and for malignant tumors In the head and neck it was 2. 4:1. The most frequently involved site by the malignant tumors were :nasopharynx, mouth, maxillofacial regions, and neck. THe majority (62. 65%) of malignant tumors were located in the nasopharynx which accounted for 28. 68% of all malignanties of which the ratio of mate and female was 3:1, peak age was 41-50 years, 18 of themwas under 10 years of age, the youngest was 1 1/2 years andthe oldest was 84 years old. These data showed that malignant tunors in the head and neck regions, expecially those in the nasopharynx, are common in Guanxi province, China. The program for cancer research on prevention and treatment should be enforced.

Clinicopathological and molecular insights into odontogenic tumors associated with syndromes:A comprehensive review

The association between genetic syndromes and odontogenic tumors encompasses several entities,reflecting the intricate interplay between genetic factors and the development of these lesions.The present study aimed to comprehensively investigate the associations between genetic syndromes and odontogenic tumors.We delineated the diverse spectrum of syndromic connections,including key syndromes such as Gardner syndrome,Gorlin syndrome,Schimmelpenning syndrome,and others.Our findings underscore the clinical significance of recognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention.We advocate for multidisciplinary collaboration among clinicians,geneticists,and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations.In light of this,our study contributes to the growing body of knowledge in dentistry and medical genetics,offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors.

Prototyping: Major Advance in Surgical Planning and Customizing Prostheses in Patients with Bone Tumors of the Head and Neck

Major resections of bone tumors of the head and neck, owing to their small dimensions and their proximity to the organs in this region, cause important functional and aesthetic problems that significantly compromise patients’ quality of life. Therefore, therapeutic planning should always extend beyond the resection to include functional and aesthetic reconstruction, preferably immediately. Microsurgical reconstruction represents a significant advance, but has not yet been perfected. Rapid prototyping (RP) comes as a new technology for the purpose of assisting the surgeon in the visual and tactile aspects of surgery, providing diagnostic accuracy and increasing the success of surgical planning. The authors demonstrate the technological advances in the manufacture of customized mandibular prostheses with the assistance of RP and practical applications of these methods.

Duodenum-preserving resection and Roux-en-Y pancreatic jejunostomy in benign pancreatic head tumors

This study was conducted to explore the feasibility of partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of benign tumors of the pancreatic head(BTPH). From November 2006 to February 2009, four patients(three female and one male) with a mean age of 34.3 years(range: 21-48 years) underwent partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of BTPH(diameters of 3.2-4.5 cm) using small incisions(5.1-7.2 cm). Preoperative symptoms include one case of repeated upper abdominal pain, one case of drowsiness and two cases with no obvious preoperative symptoms. All four surgeries were successfully performed. The mean operative time was 196.8 min(range 165-226 min), and average blood loss was 138.0 m L(range: 82-210 m L). The mean postoperative hospital stay was 7.5 d(range: 7-8 d). In one case, the main pancreatic duct was injured. Pathological examination confirmed that one patient suffered from mucinous cystadenoma, one exhibited insulinoma, and two patients had solid-pseudopapillary neoplasms. There were no deaths or complications observed during the perioperative period. All patients had no signs of recurrence of the BTPH within a follow-up period of 48-76 mo and had good quality of life without diabetes. Partial pancreatic head resection with Roux-en-Y pancreatic jejunostomy is feasible in selected patients with BTPH.

Trochanter/calcar preserving reconstruction in tumors involving the femoral head and neck

AIM: To evaluate the results of hip reconstruction with extensive excision for tumor confined to the femoral head and neck. METHODS: We designed a resection preserving the greater trochanter and lower portion of calcar femorale, and utilized conventional total hip prosthesis. We retrospectively reviewed 7 patients, who underwent a wide resection and reconstruction using conventional hip prosthesis. There were 3 men and 4 women and their mean age was 42.5 years(22 to 65 years). The histologic diagnosis of each patient was low-grade osteosarcoma, diffuse large B-cell lymphoma, liposclerosing myxofibroma, intraosseous lipoma, chondroblastoma, giant cell tumor and focal intramedullary fibrosis. RESULTS: One patient with lymphoma died due to disease dissemination at 10 mo postoperatively and the remaining 6 patients were followed for a mean of 4.7 years(3 to 6 years). All patients were able to return to their daily activities and no patient had local recurrence. No radiographic signs of loosening, wear, and osteolysis were found at the last follow-up. CONCLUSION: Trochanter/calcar-preserving resectionof the proximal femur and reconstruction using conventional total hip prosthesis, is a satisfactory treatment for tumors confined to the femoral head and neck.

Collision tumor of squamous cell carcinoma and neuroendocrine carcinoma in the head and neck:A case report

BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and squamous cell carcinoma(SCC)in the nasal cavity and paranasal sinus.She received operation,concurrent chemoradiotherapy,and then two cycles of palliative chemotherapy.Follow-up at 12 mo after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis.A literature review of previous 26 cases diagnosed with collision tumor of NEC and SCC in the head and neck was also undertaken.CONCLUSION It is challenging to manage collision tumors because there are two morphologically and etiologically distinct tumors.Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

MANAGEMENT OF HEAD AND NECK TUMORS

The experience of management of head and neck tumors was summarized by author’s and some other Chinese literatures. This paper mainly introduced the epidemiology, diagnosis, treatment and prognosis of head and neck tumors, especially the malignancies in China. It emphasized that to assign protocols on a case-by-case basis (custom made) and the combined therapy are key points to improve the cure rate or survival rate for head and neck malighancies. Up to now, the 5-year survival rate for squamous cell carcinoma of head and neck was about 62% (1986), and about 71% (1987) for carcinoma of salivary gland origin.

Clinicopathological and Prognostic Significance of Circulating Tumor Cells in Patients with Head and Neck Cancer: A Meta-Analysis

Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.

Research Progress in Surgical Management of Head and Neck Tumors Involving the Carotid Artery

The surgeons adopt the comprehensive treatment method basing on surgery When head and neck tumors involve the carotid artery. At present, there are four surgical treatments, namely, dissection of carotid artery tumor, resection of carotid artery, revascularization after carotid resection, endoarterial implantation of covered stent combined with surgical resection. However, there is currently no consensus on the standard surgical approach to choose. This paper describes the four surgical methods, which are expected to be helpful for head and neck surgeons to choose the surgical methods for head and neck tumors involving the carotid artery.

A pilot study of the relative number of circulating tumor cells and leukocytes containing actin-binding proteins in head and neck cancer patients

Circulating tumor cells(CTCs)play an important role in tumor metastases,which is positively correlated with an increased risk of death.Actin-binding proteins,including cofilin(CFL1),profilin 1(PFN1),and adenylate cyclase-associated protein 1(CAP1),are thought to be involved in tumor cell motility and metastasis,specifically in head and neck squamous cell carcinoma(HNSCC).However,currently,there are no published studies on CFL1,PFN1,and CAP1 in CTCs and leukocytes in HNSCC patients.We assessed serum levels of CFL1,PFN1,and CAP1 and the number of CTCs and leukocytes containing these proteins in blood from 31 HNSCC patients(T1-4N0-2M0).The analysis used flow cytometry and an enzyme-linked immunosorbent assay kit.We found that CAP1+CTCs and CAP1+leukocyte subpopulations were prevalent in these HNSCC patient samples,while the prevalence rates of CFL1+and PFN1+CTCs were relatively low.Patients with stage T2-4N1-2M0 had CFL1+and PFN1+CTCs with an elevated PFN1 serum level,compared with the T1-3N0M0 group.In summary,the PFN1 serum level and the relative number of PFN1+CD326+CTCs could be valuable prognostic markers for HNSCC metastases.The current study is the first to obtain data regarding the contents of actin-binding proteins(ABPs)in CTCs,and leukocytes in blood from HNSCC patients.This is also the first to assess the relationship between the number of CTCs subgroups and disease characteristics.

Clinicopathological study of malignant peripheral nerve sheath tumors in the head and neck:Case reports and review of literature

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.

A CLINICAL ANALYSIS OF 7878 PATIENTS WITH TUMORS IN THE HEAD AND NECK

7878 patients with tumors in the head and neck were analyzed in a period of twenty years. All the diagnosis were confirmed by pathologic examination. There were 5485 cases (69.62%) of malignant tumors. Nearly an half of malignant tumors were in the nasopharynx (49.32%). Among the malignant tumors of the nasopharynx, 2698 were carcinoma (99.34%) and only 18 (0.66%) sarcoma. Nine of them were under 10 years of age, the youngest patient was 3 years old, and this is rare in our county. The incidence of head and neck tumors was 37.66% and that of the head and neck malignancies was 26.22% of tumors in the whole body. This study indicates that incidence of malignant tumor in head and neck was rather higher, it is worth to improve ths procedure of treatment and prevention.

A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor

Gastrointestinal stromal tumor (GIST) represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 (c-kit protein) positivity at immunohistochemistry. Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST, which was assessed as a pancreatic head tumor preoperatively.

Potential roles of tumor suppressor genes and microsatellite instability in hepatocellular carcinogenesis in southern African blacks

MAJOR POINTS OF THE COMMENTED ARTICLECumulative loss of heterozygosity(LOH)ofchromosomal regions and tumor suppressor geneshas been reported in hepatocellular carcinomas(HCCs) from China,Japan,and Korea.In thisissue of the World Journal of Gastroenterology,Martins et al report an analysis of LOH andmicrosatellite instability in HCCs from a group of

Postoperative secondary aggravation of obstructive sleep apneahypopnea syndrome and hypoxemia with bilateral carotid body tumor:A case report

BACKGROUND Carotid body tumor(CBT)is a chemoreceptor tumor located in the carotid body,accounting for approximately 0.22%of head and neck tumors.Surgery is the main treatment method for the disease.CASE SUMMARY We reviewed the diagnosis and treatment of one patient who had postoperative secondary aggravation of obstructive sleep apnea–hypopnea syndrome(OSAHS)and hypoxia after surgical resection of bilateral CBTs.This patient was admitted,and relevant laboratory and imaging examinations,and polysomnography(PSG)were performed.After the definitive diagnosis,continuous positive airway pressure(CPAP)treatment was given,which achieved good efficacy.CONCLUSION This case suggested that aggravation of OSAHS and hypoxemia is possibly caused by the postoperative complications after bilateral CBTs,and diagnosis by PSG and CPAP treatment are helpful for this patient.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

Duodenal gastrointestinal stromal tumors(GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography(EUS) and fine-needle aspiration(FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

Direct intratumoral embolization of hypervascular tumors of the head and neck

To evaluate a devascularization technique for hypervascular tumors of the head and neck by direct intratumoral puncture Methods Six cases of hypervascular tumor of the head and neck were reviewed, focusing on findings from digital subtraction angiography and preoperative direct intratumoral embolization and their effects after the operation Results Total devascularization by complete embolization was achieved in 2 cases: 1 nasopharyngeal angiofibroma and 1 spongiform tumor, both of which were completely excised endoscopically with blood loss of 60 ml Incomplete devascularization through 80%-90% embolization was achieved in the other 4 cases: 1 paraganglioma was totally removed with 800 ml of blood loss, 1 hemangioblastoma was not completely excised with 400 ml of blood loss and 2 nasopharyngeal angiofibromas involving the intracranial region were partially eliminated with a total blood loss of 1600 ml Conclusion The new technique of preoperative embolization of hypervascular tumors of the head and neck by direct intratumoral puncture, which can decrease blood loss during the accompanying tumor resection and increase the possibility of complete tumor removal, is feasible, convenient, safe, and effective