pN status predicts outcomes in surgically treated pT1-pT2 patients of various disease stages with squamous cell carcinoma of the head and neck: a 17-year retrospective single center cohort study.

OBJECTIVES: The optimal treatment for a substantial proportion of patients with pT1-pT2 squamous cell carcinomas of the head and neck (SCCHN) remains to be refined. The extent of surgery, role and potential benefit of adjuvant treatment are to be balanced against therapy-induced side effects. We compared the outcomes of surgery with or without adjuvant radiotherapy (RT) or chemotherapy (CRT) and investigated the prognostic value of established clinicopathological parameters. METHODS: Data were retrospectively collected for 227 patients who were treated by surgery alone (n = 31), RT (n = 87) and CRT (n = 109) in a single center. RESULTS: Patients with stage I/II disease who had received adjuvant RT showed a better disease-free survival (DFS) (P = 0.04) than those who had received adjuvant CRT treatment. Conversely, patients with stage III/IV disease who had received CRT showed a better overall survival (OS) (P = 0.003) and DFS (P = 0.03) than those who had received surgery alone or adjuvant RT without chemotherapy. Survival analysis demonstrated that patients with pN0 to pN1 had better OS (P = 0.02), disease-specific survival (DSS) (P = 0.003), DFS (P = 0.02) and metastases free survival (MFS) (P = 0.002) compared to patients with pN2 to pN3. Multivariate analysis showed that the pN status was an independent factor for OS (P = 0.03), DSS (P = 0.04), relapse-free survival (P = 0.03), DFS (P = 0.03). CONCLUSION: The pN status is the most important prognostic factor for pT1 to pT2 SCCHN. Adjuvant CRT was associated with significantly better survival outcomes in patients with pN1 and pN2-3 or more advanced stage, while adjuvant RT showed significantly better outcomes in patients with pN0.

Dentin as a suitable bone substitute comparable to ß-TCP--an experimental study in mice.

Microvascular supply is of fundamental importance to the survival and integration of grafting. Since the autogenous bone is still the gold standard for osseous augmentation, the aim of this study was to analyze the initial osseous, angiogenic and inflammatory response and subsequent osseointegration after implantation of dentin and beta-tricalcium phosphate (ß-TCP) scaffolds into the calvaria chamber of balb/c mice comparing with bone. The vascularisation of perforated implants of dentin (n=8), ß-TCP (n=8) and isogenic calvarial bone (n=8) displaying pores similar in size and structure was analyzed in vivo using intravital fluorescence microscopy. In additional animals (n=24) the osseointegration of dentin, ß-TCP and bone implants was assessed by fluorochrome sequential labelling of growing bone for up to 12 weeks. Animals without implants served as controls. Intravital fluorescence microscopy revealed that implantation of bone substitutes caused an only mild inflammatory response. Comparable to isogenic bone both dentin and ß-TCP scaffolds were found nearly completely vascularized by day 22 and osseointegrated within 12 weeks. In conclusion, dentin and ß-TCP scaffolds are similar to isogenic bone in terms of inflammatory and neovascularization response, highlighting their potential utility in regeneration of bone defects.

Quality of life in school-age children with orofacial clefts and their families.

Nonsyndromic orofacial clefts might affect family functioning and probably reduce the quality of life in school-age children and their parents. One hundred seventy consecutive children with orofacial clefts between 8 and 12 years and their families were asked to answer the Impact on Family Scale and KINDL. The results were compared with the quality of life in an age- and sex-matched group of unaffected schoolchildren. One hundred thirty-two families participated in this study. Family functioning was found superior in families with children with cleft lip than in families with children with cleft palate only or cleft lip and palate. Sex had no significant influence on family functioning. The quality of life in schoolchildren with orofacial clefts was found superior to the control group. Reductions were observed in children with cleft lip and palate in the dimensions "family" and "friends," indicating problems in the social field. Boys with orofacial clefts experienced a lower quality of life than girls. Children with cleft lip and palate and cleft palate only experienced a lower quality of life than children with cleft lip. Even years after successful cleft reconstruction, coping and mastering the diagnosis of orofacial cleft is a relevant concern for affected families. Several limitations of the quality of life in schoolchildren were identified, mostly affecting their social role.

Prognostic Score Predicts Survival in HPV-Negative Head and Neck Squamous Cell Cancer Patients.

Although patients having head and neck squamous cell carcinoma (HNSCC) have high mortality, standardized prognostic tools are unavailable. As such, having a validated simple prognostic scoring system to help predict mortality in these high-risk patients is urgently needed. The current study aimed to develop and internally validate a prognostic scoring system for overall mortality in human papillomavirus (HPV)-independent HNSCC patients. Data on 400 consecutive patients from the Cancer Genome Atlas database with a known HPV-RNA negative status were analyzed. A prognostic model to predict patient overall mortality was developed using the logistic regression beta coefficients and a simple risk score was created. The model was internally validated using bootstrap validation with 2000 replications. Five covariates (age, pT, pN, perineural invasion, and EAp53 score) were used in the development of the mortality risk score in the final model. Three risk groups were stratified based on the prognostic scores: low-risk (<96 points), medium-risk (96-121 points), and high-risk (≥122 points) with a survival of 76%, 62% and 35%, respectively. The proposed model presented good discrimination in both the development (AUC = 0.76; 95% CI 0.70, 0.81) and bootstrap validation (AUC = 0.76; 95% CI 0.70, 0.81) with a non-significant Hosmer-Lemeshow chi-square of 6.17 (p = 0.63). The proposed prognostic scoring system is easy to use to predict patient overall mortality and could also help in the appropriate allocation of medical resources while managing HNSCC patients. External validation (including re-calibration if needed) should be conducted to test the model's generalizability in different populations.

Head and neck tuberculosis: Literature review and meta-analysis.

BACKGROUND: Head and neck tuberculosis (HNTB), including cervical lymphadenopathy, is the most common extrapulmonary manifestation of TB. The proposed study investigated the epidemiologic and clinical characteristics of HNTB. MATERIALS AND METHODS: A literature search was conducted via PubMed, Embase, Cochrane Library and Wanfang for keywords (tuberculosis, head and neck, laryngeal, pharyngeal, tongue, oropharyngeal, nasopharyngeal, and oral cavity). Scientific articles published from January 1990 through July 2017 were selected and reviewed to assess the epidemiology, presentation, diagnosis and treatment of HNTB disease. RESULTS: Results from the included 57 studies revealed that the majority of HNTB cases were age<40 years and female. The most common HNTB sites were cervical lymph nodes (87.9%), followed by larynx (8.7%). Involvement of other HN-regions was rare (3.4%). Multidrug resistant TB was not common among the majority of studies. Given the paucibacillary nature of HNTB, sputum tests did not have a good performance on HNTB diagnosis. Most of HNTB cases were diagnosed by fine-needle aspiration, cytology and excision biopsies in combination with clinical presentations. CONCLUSION: HNTB disease is an important manifestation in the diagnostic process in an otolaryngologist practice. The developments of rapid, ultrasensitive, simple and cost-effective high-throughput methods for early diagnosis of HNTB are urgently needed.

Experimental application of a biomaterial in bifocal transport osteogenesis for craniofacial reconstruction.

PURPOSE: Bifocal transport osteogenesis is an alternative technique of callus distraction, in which movement of a transport segment results in the formation of new bone in order to close a continuity defect. The aim of this experimental pilot study was to replace a bone graft by a biomaterial as a transport segment. MATERIAL AND METHODS: Critical size defects of the calvaria in four adult sheep were treated with transport segments consisting either of an autogenous free bone graft of the calvaria (n=2) or of the biomaterial (deproteinized bovine cancellous bone; n=2). Latency period was 5 days; the rate of distraction was 1mm per day and was planned for 40 days. The consolidation period was 28 days. Specimens were investigated by conventional radiography, CT-scans and histologically, including immunofluorescence. RESULTS: In both groups, transport osteogenesis resulted in a "de novo" formation of bone, indicating that this biomaterial may contribute successfully to bone formation in bifocal transport osteogenesis. However, volume and thickness of the newly formed bone at the defect site were smaller when using the biomaterial than when using autogenous bone grafts. CONCLUSION: The application of a biomaterial as transport segments in bifocal transport osteogenesis in cranial critical size defects resulted in the formation of new bone thus excluding bone graft donor site morbidity.

Calvaria bone chamber--a new model for intravital assessment of osseous angiogenesis.

The faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation of angiogenesis are described, none of them allows the observation of new vessel formation in desmal bone. Therefore, we developed a new chamber model suitable for quantitative in vivo assessment of the vascularization of bone substitutes by intravital fluorescence microscopy. In the parietal calvaria of 32 balb/c mice a critical size defect was set. Porous 3D-poly(L-lactide-co-glycolide) (PLGA)-blocks were inserted into 16 osseous defects (groups 3 and 4) while other 16 osseous defects remained unequipped (groups 1 and 2). By placing a polyethylene membrane onto the dura mater, the angiogenesis was mainly restricted to the osseous margins (groups 2 and 4). Microvascular density, angiogenesis, and microcirculatory parameters were evaluated repetitively during 22 days. In all animals, only a mild inflammatory reaction was observed with a climax after 2 weeks. The implantation of PLGA scaffolds resulted in a vascular growth directed towards the center of the defect as demonstrated by the significantly (p < 0.05) enhanced central microvascular densitiy from day 3 to day 22 when compared with unequipped chambers. The additional application of polyethylene membrane was found to reduce significantly the microvessel density mainly in the center of both scaffolds and defects. The present calvaria bone chamber allows for the first time to assess quantitatively the angiogenesis arising from desmal bone directly in vivo. Therefore, this chronic model may support the future research in the biological adequacy of bone substitutes.

Accelerated angiogenic host tissue response to poly(L-lactide-co-glycolide) scaffolds by vitalization with osteoblast-like cells.

BACKGROUND: Bone substitutes should ideally promote rapid vascularization, which could be accelerated if these substitutes were vitalized by autologous cells. Although adequate engraftment of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds has been demonstrated in the past, it has not yet been investigated how vascularization is influenced by vitalization or, more precisely, by seeding PLGA scaffolds with osteoblast-like cells (OLCs). For this reason, we conducted an in vivo study to assess host angiogenic and inflammatory responses after the implantation of PLGA scaffolds vitalized with isogeneic OLCs. MATERIALS AND METHODS: OLCs were seeded on collagen-coated PLGA scaffolds that were implanted into dorsal skinfold chambers in BALB/c mice (n = 8). Two further groups of animals received either collagen-coated (n = 8) or uncoated PLGA scaffolds (n = 8). Animals that received chambers without implants served as controls (n = 8). Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed for 14 days using intravital fluorescence microscopy. RESULTS: PLGA scaffolds with and without OLCs showed a temporary increase in leukocyte recruitment. At day 3 after implantation, a marked angiogenic host tissue response was observed in close vicinity of all scaffolds studied. At days 6 and 10, the angiogenic response was significantly higher (p < 0.05) in PLGA scaffolds vitalized with OLCs than in uncoated or collagen-coated PLGA scaffolds. The majority of OLCs, however, died within 14 days after implantation. CONCLUSION: Our study demonstrates that PLGA scaffold vitalization with OLCs accelerates the angiogenic response in the surrounding host tissue. Bone substitutes created by tissue engineering may thus be superior to nonvitalized substitutes although the seeded cells do not survive for long periods.

Osseous alterations at the interface of hydrogel expanders and underlying bone.

INTRODUCTION: In plastic and reconstructive surgery, self-activating hydrogel expanders are used to augment soft-tissue space. The purpose of this study was to investigate the morphological response of underlying bone to the constant pressure exerted by a hydrogel expander. METHODS: Eighteen Lewis rats were randomly divided into three groups. In group 1, a hydrogel expander was placed subperiosteally directly onto the calvaria of the rats. In group 2, the expander and the underlying bone were separated by a polydioxanone (PDS) foil. Group 3 animals served as controls. Before and 14 days after the insertion of the expanders, micro-computed tomography (CT) images were obtained and fused. We analysed hydroxyapatite density beneath and at the periphery of the expander and performed a histomorphometric bone analysis. RESULTS: Whereas there were no significant differences (p<0.05) (groups 1 and 2) in bone density at the periphery of the expanders between the study groups, a significant decrease in hydroxyapatite density beneath the expanders was observed in those animals in which the devices were placed directly onto the calvaria (group 1). Whereas bone thickness was unaffected at the periphery of the expanders in all groups, it was significantly decreased beneath the expanders in all implanted animals. A morphological examination revealed resorption lacunae with a diameter of 218.4+/-56 mICROm in those rats in which the expanders had been placed directly onto the calvaria. CONCLUSION: This study shows the direct influence of hydrogel expanders on underlying bone. Whereas bone resorption and connective tissue formation also occur underneath hydrogel expanders, these effects can be avoided if the expander and the underlying bone are separated by PDS foil. The key to success is to ensure the appropriate placement of expanders and thus to avoid bone resorption.

Quality of life and family functioning in children with nonsyndromic orofacial clefts at preschool ages.

Children with orofacial clefts (OFC) at preschool ages may have to tolerate psychosocial disadvantages due to their altered speech and facial appearance probably affecting their quality of life (QoL) and family functioning. In 147 children with OFC aged between 5 and 6 years and their families, the QoL and family functioning were analyzed using the KINDL questionnaire for measuring health-related QoL in children and impact on family scale. The KINDL scores were lowest in the dimension self-esteem. In all dimensions, the KINDL scores of children were higher than those of the parents suggesting a superior QoL than the caregivers estimated (P<0.001). In affected families, the impact on family scale dimensions personal impact and impact on coping strategies were found highest. Families having children with isolated cleft lip or cleft lip and palate had higher impacts on coping strategies when compared with children having isolated cleft palate (P<0.041). The impact for siblings (P<0.02) was found highest in patients with cleft lip and palate. In all examined dimensions, children with OFC perceived a higher QoL than their caregivers expected. However, self-esteem seems to be problematic in all types of OFC and in both genders. Knowledge of potential impacts related to the type of cleft and the gender of the patient will probably facilitate health care professionals to identify children and families at high risk to experience a reduced QoL and may help to offer specific support and treatment strategies.