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.

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.

PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

Paclitaxel for second-line treatment of squamous cell carcinoma of the head and neck:A multicenter retrospective Italian study

BACKGROUND Squamous cell carcinoma of the head and neck(SCCHN)accounts for 3%of all malignant tumors in Italy.Immune checkpoint inhibitors combined with chemotherapy is first-line treatment for SCCHN;however,second-line treatment options are limited.Taxanes are widely used for combination therapy of SCCHN,as clinical trials have shown their efficacy in patients with this disease,partic ularly in patients with prior therapy.AIM To perform a multicenter retrospective study on the efficacy and safety of weekly paclitaxel for SCCHN.METHODS All patients were previously treated with at least one systemic therapy regimen,which included platinum-based therapy in the vast majority.No patient received prior immunotherapy.RESULTS Median progression-free survival(mPFS)was 3.4 months and median overall survival(mOS)was 6.5 months.Subgroup analysis was performed according to three principal prognostic factors:Smoking,alcohol consumption,and body mass index.Analysis demonstrated reduced survival,both mOS and mPFS,in the unfavorable prognostic groups,with the biggest deltas observed in mOS.CONCLUSION Weekly paclitaxel provided favorable survival and disease control rates,with low severe adverse events.Paclitaxel is a safe and valid therapeutic option for patients with SCCHN who received prior therapy.

Treatment of a femoral neck fracture combined with ipsilateral femoral head and intertrochanteric fractures: A case report

BACKGROUND This article presents a rare case of a complex hip fracture involving the ipsilateral femoral neck,trochanter,and femoral head,that was accompanied by hip dislocation.Currently,there is no established standard treatment method for this specific type of fracture.Therefore,it is crucial to comprehensively consider factors such as patient age,fracture type,and degree of displacement to achieve a successful outcome.CASE SUMMARY A 38-year-old man sustained a comminuted fracture of his right hip as a result of a car accident.The injuries included a fracture of the femoral head,a fracture of the femoral neck,an intertrochanteric fracture of the femur,and a posterior dislocation of the hip on the same side.We opted for a treatment approach combining the use of a proximal femoral locking plate,cannulated screws,and Kirschner wires.Following the surgery,we developed an individualized rehabil-itation program to restore patient limb function.CONCLUSION For this complex fracture,we selected appropriate internal fixation and for-mulated individualized rehabilitation,which ultimately achieved good results.

Effect of Mouth Opening Training Stick Combined with Oral Massage on Mouth Opening Difficulty in Head and Neck Cancer Patients after Treatment

Objective: To study the application effect of mouth-opening training sticks combined with oral massage on patients with mouth-opening difficulty after treatment for head and neck cancer. Methods: Using convenient sampling, 60 patients with mouth-opening difficulty after treatment for head and neck cancer admitted to the Oncology Department from February 2022 to October 2023 were selected for a 2-week exercise and nursing program. The patients were divided into a control group (February 1, 2022 to November 30, 2022) and an observation group (December 1, 2022 to October 31, 2023), with 30 patients in each group. The control group underwent routine mouth-opening functional exercises combined with cork for oral support training, while the observation group underwent routine mouth-opening functional exercises combined with oral massage and mouth-opening training sticks for oral support training. The mouth-opening degree, mouth-opening difficulty level, comfort level, compliance, and quality of life were observed in both groups. Results: Before the intervention, there were no statistically significant differences in mouth-opening degree and mouth-opening difficulty level between the two groups (P > 0.05). After the intervention, the mouth-opening degree, mouth-opening difficulty level, oral comfort level, compliance, and QLICP-HN scores in the observation group were all better than those in the control group, with statistically significant differences (P < 0.05). Conclusion: The combination of mouth-opening training sticks and oral massage with mouth-opening functional exercises can effectively improve the degree of mouth-opening difficulty, enhance oral comfort, increase compliance with mouth-opening exercises, and improve quality of life.

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.

Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Epidemiology and Histopathology of Cancers of the Upper Aerodigestive Tract in the ENT and Head and Neck Surgery Department of the Ignace Deen National Hospital

Introduction: Head and neck cancers represent a significant burden of cancer, collectively ranking fourth for cancer incidence and second for cancer mortality worldwide. Objective: To study the epidemiological and histopathological aspects of head and neck cancers in the ENT-CCF department of Ignace Deen National Hospital. Materials and Methods: This was a descriptive retrospective study covering a period of 5 years from September 1, 2016, to September 30, 2021. Results: We collected 43 cases of head and neck cancers, representing a hospital frequency of 1.85%. The mean age was 45.21 ± 13.23 years. Males predominated, accounting for 65.12%, compared to 34.88% for females, with a male-to-female ratio of 1.87. Housewives accounted for 27.90%, followed by farmers at 23.26% and traders/merchants at 18.60%, with 41.86% being uneducated. The main risk factors were tobacco (37.21%) and alcohol (34.88%). Pain (53.49%), dysphonia (51.16%), and dyspnea (39.53%) were the main presenting symptoms. Squamous cell carcinoma (74.42%) and large cell lymphoma (18.60%) were the most commonly cited histological types. Conclusion: Head and neck cancers remain relatively common in our country. Improving prognosis depends on early diagnosis of the condition, resuscitation resources, and prompt management.

PTEN as a Novel Diagnostic and Prognostic Biomarker of Head and Neck Squamous Cell Carcinoma

This review article explores phosphatase and tensin homolog(PTEN)’s role in head and neck squamous cell carcinoma(HNSCC)through comprehensive expression and methylation examinations,genetic mutation investigation,and prognostic evaluation.Using the UALCAN informational collection,PTEN expression examination uncovered a critical over-expression in HNSCC cells isolated from normal control samples,proposing its role in HNSCC multiplication.Further,analysis of PTEN expression across various clinical limits has shown critical up-regulation in different cancer development stages,racial groups,gender,and age classes within the context of HNSCC patients,suggesting its major role in cancer duplication.PTEN expression was validated by utilizing the GEPIA2.0 online tool,which showed PTEN expression was particularly significantly expressed in HNSCC cancer improvement when it appeared differently from normal control samples.Accordingly,examining PTEN validation across different phases of cancer advancement showed dysregulation in each of the four phases with the most raised expression in stage I and the least expression in stage IV.Thus,this study investigated the promoter methylation level of PTEN,figuring out a basic relationship between HNSCC samples and normal control samples.Analyzing promoter methylation across various clinical limits uncovered massive variations,with specific methylation patterns seen across malignant growth stages,race groups,gender,and age groups.Overall survival and disease-free survival(OS and DFS)utilizing the KM plotter tool showed a critical relationship between PTEN expression levels in HNSCC patients,showing high PTEN expression exhibited good overall survival when showed up distinctively comparable to low PTEN expression levels.In addition,in disease-free survival(DFS)evaluation HNSCC patients showing low PTEN expression experienced great DFS relative to HNSCC patients with high PTEN expression.Moreover,to validate PTEN expression against survival,the study examined the HNSCC patients into low and high-expression groups of PTEN.In HNSCC,low PTEN expression was connected with great overall survival(OS)when it appeared contrastingly relative to the high PTEN expression.In like manner,the study found that low PTEN expression level was connected with great DFS in HNSCC when it appeared contrastingly related to the high PTEN expression group.Genetic mutation analysis via cBioPortal identifies a minimal proportion of PTEN mutations in HNSCC,predominantly in-frame mutation,missense mutation,splice mutation,truncating mutation,and structural variant,indicating their basal significance in PTEN dysregulation within HNSCC.Further investigation of PTEN molecular components and their exchange inside the HNSCC microenvironment might disclose novel roads for designated treatment and accurate medication approaches in battling this harmful disease.

ATM is a Prognostic Biomarker of Survival in Head and Neck Squamous Cell Carcinoma Patients

This review examines the role of ATM expression in head and neck squamous cell carcinoma(HNSCC).Analysis revealed significant overexpression of ATM in HNSCC cells compared to normal control samples,suggesting its involvement in cancer proliferation.ATM expression was notably upregulated across various clinical parameters,including different stages of cancer,racial groups,genders,and age groups,highlighting its role in cancer progression.Validation using the GEPIA2 tool confirmed strong ATM expression throughout all four stages of HNSCC,with the highest levels in stage II and the lowest in stage I.Promoter methylation analysis of ATM showed distinct patterns across different demographics and cancer stages,reinforcing its significance.The study also explored the relationship between ATM expression and patient outcomes using the KM plotter tool,finding that high ATM expression was associated with better overall survival(OS),while low ATM expression correlated with better disease-free survival(DFS).Genetic mutation analysis via cBioPortal identified minimal ATM mutations in HNSCC,including in-frame,splice,truncating,and missense mutations,suggesting their role in ATM dysregulation.The STRING tool was used to construct a protein-protein interaction(PPI)network,revealing that the ATM gene interacts with ten key genes(NBN,ATR,CHEK2,MDC1,MSH2,MSH6,MRE11,TP53,TP53BP1,BRCA1),indicating its involvement in various biological functions.Functional annotation of differentially expressed genes(DEGs)through the DAVID web server revealed their participation in critical biological processes,including double-strand break repair,cellular response to DNA damage,and DNA damage checkpoints.KEGG pathway analysis further linked DEGs to cellular senescence,platinum drug resistance,homologous recombination,p53 signaling,and the cell cycle,underscoring ATM’s multifaceted role in HNSCC.

Oral and maxillofacial-head and neck reconstruction with soft tissue free flaps of 41 cases: A single team's experience

Objective To retrospectively review the single team's experience of oral and maxillofacialhead and neck reconstruction involving 41 soft tissue free flap procedures.Methods From 1994 to 2012,41 patients who underwent oral and maxillofacial-head and neck soft tissue free flap reconstruction at the Department of Oral and Maxillofacial-Head and Neck Surgical Oncology,Hospital and College of Stomatology,Xi'an Jiaotong University,were reviewed with clinicopathologic data.Results The 41 patients included 24 men and 17 women with a mean age of 54 years.A total of 41 soft tissue free flaps were performed to reconstruct different anatomical structures in the head and neck region including oral mucosa,facial bone,head and neck skin.Two types of soft tissue free flaps were used to reconstruct surgical defects,including radial forearm flap and latissimus dorsi myocutaneous flap.Radial forearm flaps were used for 37cases and latissimus dorsi-myocutaneous flaps were 4 cases.Of 41 cases,39 were successful,with an overall success rate of 95.1%.There were 2 free flap failures,including one radial forearm flap and one latissimus dorsi-myocutaneous flap(partial flap necrosis);hence,the flap success rates for radial forearm flap and latissimus dorsimyocutaneous were,respectively,97.3% and 87.5%.Conclusions Radial forearm flap and latissimus dorsi-myocutaneous flap are reliable soft tissue free flaps to repair oral and maxillofacial-head and neck area with high success rate,which resulted in good functionally and cosmetically with fewer complications both donor and recipient sites.

Downregulation of iASPP Expression Suppresses Proliferation, Invasion and Increases Chemosensitivity to Paclitaxel of Head and Neck Squamous Cell Carcinoma In Vitro

Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma(HNSCC)and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC.This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro.Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group,respectively.The non-infected Tu686 cells were named the CON group.CCK-8 assay,flow cytometry,transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro.Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h(F=32.459,P=0.000),96 h(F=51.407,P=0.000),120 h(F=35.125,P=0.000)post-transfection,was significantly lower than that of shRNANC cells and CON cells.The apoptosis ratio of shRNA-iASPP cells was 9.42%±0.39%(F=299.490,P=0.000),which was significantly higher than that of CON cells(2.80%±0.42%)and shRNA-NC cells(3.18%±0.28%).The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65%±1.09%(F=388.901,P=0.000),which was strikingly increased,compared with that of CON cells(55.19%±1.02%)and shRNA-NC cells(54.62%±0.88%).The number of invading cells was 56±4 in the shRNA-iASPP group(F=84.965,P=0.000),which decreased significantly,compared with the CON group(111±3)and the shRNA-NC group(105±8).The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased,compared with CON cells and shRNA-NC cells(F=634.841,P=0.000).Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.

Fatal complications in a patient with severe multi-space infections in the oral and maxillofacial head and neck regions: A case report

BACKGROUND Odontogenic infection is one of the common infectious diseases in oral and maxillofacial head and neck regions.Clinically,if early odontogenic infections such as acute periapical periodontitis,alveolar abscess,and pericoronitis of wisdom teeth are not treated timely,effectively and correctly,the infected tissue may spread up to the skull and brain,down to the thoracic cavity,abdominal cavity and other areas through the natural potential fascial space in the oral and maxillofacial head and neck.Severe multi-space infections are formed and can eventually lead to life-threatening complications(LTCs),such as intracranial infection,pleural effusion,empyema,sepsis and even death.CASE SUMMARY We report a rare case of death in a 41-year-old man with severe odontogenic multi-space infections in the oral and maxillofacial head and neck regions.One week before admission,due to pain in the right lower posterior teeth,the patient placed a cigarette butt dipped in the pesticide"Miehailin"into the"dental cavity"to relieve the pain.Within a week,the infection gradually spread bilaterally to the floor of the mouth,submandibular space,neck,chest,waist,back,temporal and other areas.The patient had difficulty breathing,swallowing and eating,and was transferred to our hospital as an emergency admission.Following admission,oral and maxillofacial surgeons immediately organized consultations with doctors in otolaryngology,thoracic surgery,general surgery,hematology,anesthesia and the intensive care unit to assist with treatment.The patient was treated with the highest level of antibiotics(vancomycin)and extensive abscess incision and drainage in the oral,maxillofacial,head and neck,chest and back regions.Unfortunately,the patient died of septic shock and multiple organ failure on the third day after admission.CONCLUSION Odontogenic infection can cause serious multi-space infections in the oral and maxillofacial head and neck regions,which can result in multiple LTCs.The management and treatment of LTCs such as multi-space infections should be multidisciplinary led by oral and maxillofacial surgeons.

Incidence and analysis of radial head and neck fractures

AIM: To investigate several complications like persistent radial head dislocation, forearm deformity, elbow stiffness and nerve palsies, associated with radial head fractures. METHODS: This study reviewed the clinical records and trauma database of this level Ⅰ Trauma Center and identified all patients with fractures of the radial head and neck who where admitted between 2000 and 2010. An analysis of clinical records revealed 1047 patients suffering from fractures of the radial head or neck classified according to Mason. For clinical examination, range of motion, local pain and overall outcome were assessed. RESULTS: The incidence of one-sided fractures was 99.2% and for simultaneous bilateral fractures 0.8%. Non-operative treatment was performed in 90.4%(n = 947) of the cases, surgery in 9.6%(n = 100). Bony union was achieved in 99.8%(n = 1045) patients. Full satisfaction was achieved in 59%(n = 615) of the patients. A gender related significant difference(P = 0.035) in Mason type distribution-type Ⅲ fractures were more prominent in male patients vs type Ⅳ fractures in female patients-was observed in our study population. CONCLUSION: Mason typeⅠfractures can be treated safe conservatively with good results. In type Ⅱ to Ⅳ surgical intervention is usually considered to be indicated.

Radiation-induced sarcomas of the head and neck

With improved outcomes associated with radiotherapy, radiation-induced sarcomas(RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stagematched sarcomas that arise independent of irradiationand surgical resection with clear margins seems to offer the best chance for cure.

Lymphangiogenesis, Lymphatic Endothelial Cells and Lymphatic Metastasis in Head and Neck Cancer—A Review of Mechanisms

Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels, Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.

Clinical applications of free medial tibial flap with posterior tibial artery for head and neck reconstruction after tumor resection

Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.

Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer

AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma(HNSCC). METHODS: In this retrospective study,19 HNSCC patients underwent pre- and intra-treatment DCEMRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images,generating maps of volume transfer rate(Ktrans) and volume fraction of the extravascular extracellular space(ve). Image texture analysis was then employed on maps of Ktrans and ve,generating two texture measures: Energy(E) and homogeneity.RESULTS: No significant changes were found for the mean and standard deviation for Ktrans and ve between pre- and intra-treatment(P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans,relative to pretreatment scans(P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.