Stable fixation using absorbable sutures in craniofacial surgery in patients over 24 months of age-a retrospective study.

PURPOSE: In craniofacial surgery, the stable fixation of transposed bone segments is crucial in order to ensure good long-term results. The use of absorbable material in fixation avoids the need for a second surgery, which would otherwise be required to remove osteosynthesis material. The authors of the present manuscript have already demonstrated that absorbable sutures ensure the stable fixation of bone segments in patients up to 24 months of age. However, it has thus far remained unclear whether stable fixation is possible in older patients by using only absorbable sutures due to the slower bone remodelling and prolonged healing time in this cohort. METHOD: For the present study, osteosynthesis was performed in 50 patients ranging from 25.7 to 192.1 months of age (mean, 61.4 ± 21.7 months) using solely absorbable sutures (PDS II®, Ethicon, Germany). Post-operative stability and possible restrictions-such as foreign body reactions-were evaluated within clinical and radiological routine follow-ups. RESULTS: All children demonstrated clinically and radiologically stable osteosynthesis both directly post-operatively and in follow-ups. No significant foreign body reaction could be seen. CONCLUSION: The present study demonstrates-for the first time-that absorbable sutures with a longer absorption period are also very well suited for the fixation of bone segments in patients over 24 months of age. The sole use of absorbable sutures in children over 24 months of age is a safe procedure with nearly no foreign body reactions. The procedure enables stable and highly cost-effective osteosynthesis without altering the osteotomy design.

Performance of cone-beam computed tomography (CBCT) in comparison to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone invasion in oral squamous cell cancer (OSCC): a prospective study.

BACKGROUND: Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC. METHODS: We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities. RESULTS: Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI. CONCLUSION: Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.

Composite grafts made of polycaprolactone fiber mats and oil-based calcium phosphate cement pastes for the reconstruction of cranial and maxillofacial defects.

OBJECTIVES: Synthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured. MATERIALS AND METHODS: Bone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing. RESULTS: The process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably. CONCLUSION: PCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications. CLINICAL RELEVANCE: The complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects.

Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules.

OBJECTIVES: Magnesium phosphate-based cements begin to catch more attention as bone substitute materials and especially as alternatives for the more commonly used calcium phosphates. In bone substitutes for augmentation purposes, atraumatic materials with good biocompatibility and resorbability are favorable. In the current study, we describe the in vivo testing of novel bone augmentation materials in form of spherical granules based on a calcium-doped magnesium phosphate (CaMgP) cement. MATERIALS AND METHODS: Granules with diameters between 500 and 710 µm were fabricated via the emulsification of CaMgP cement pastes in a lipophilic liquid. As basic material, two different CaMgP formulations were used. The obtained granules were implanted into drill hole defects at the distal femoral condyle of 27 New Zealand white rabbits for 6 and 12 weeks. After explantation, the femora were examined via X-ray diffraction analysis, histological staining, radiological examination, and EDX measurement. RESULTS: Both granule types display excellent biocompatibility without any signs of inflammation and allow for proper bone healing without the interposition of connective tissue. CaMgP granules show a fast and continuous degradation and enable fully adequate bone regeneration. CONCLUSIONS: Due to their biocompatibility, their degradation behavior, and their completely spherical morphology, these CaMgP granules present a promising bone substitute material for bone augmentation procedures, especially in sensitive areas. CLINICAL RELEVANCE: The mostly insufficient local bone supply after tooth extractions complicates prosthetic dental restoration or makes it even impossible. Therefore, bone augmentation procedures are oftentimes inevitable. Spherical CaMgP granules may represent a valuable bone replacement material in many situations.

Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [18F]FDG PET/CT and MRI.

PURPOSE: While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. METHODS: Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. RESULTS: [18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. CONCLUSION: FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.

Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly.

OBJECTIVES: The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters. MATERIALS AND METHODS: The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants' cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries. RESULTS: No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries. CONCLUSIONS: Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians' more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers' subjective perceptions. CLINICAL RELEVANCE: Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.

Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy.

Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.

Craniofacial growth in infants with deformational plagiocephaly: does prematurity affect the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment?

OBJECTIVE: Although prematurity is a risk factor for developing deformational plagiocephaly (DP), to our knowledge, there are no studies that have analyzed the impact of a premature birth on the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment. MATERIALS AND METHODS: We examined 239 patients with DP who were undergoing head orthosis therapy. Depending on the gestational age, they were assigned to either a premature (gestational age of < 37 weeks) or a full-term (gestational age of ≥ 37 weeks) group. Head shape was analyzed using 3D-stereophotogrammetry at the start and end of treatment. We performed multiple linear regression analyses to evaluate the impact of prematurity on the duration of therapy and the extent of the reduction in asymmetry, taking age and the initial asymmetry of an infant's head into account. RESULTS: Head orthosis therapy led to a significant reduction in asymmetry in both groups. Using multiple linear regression analyses, we demonstrated that age at the start of treatment, the initial asymmetry and prematurity, significantly influenced the duration of therapy. Patients who were born at an earlier gestational age experienced a shorter treatment length. However, prematurity did not affect the extent of the reduction in cranial asymmetry that was achieved. CONCLUSIONS: Along with age at the start of treatment and the initial asymmetry, prematurity is significantly correlated with the duration of head orthosis therapy, but not with the extent of the reduction in asymmetry achieved. CLINICAL RELEVANCE: Knowledge of these findings is important for clinicians when planning treatment and discussing the effectiveness of head orthosis therapy with the parents of premature infants with DP.

HGF-Induced PD-L1 Expression in Head and Neck Cancer: Preclinical and Clinical Findings.

Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.

The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Methigh-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.

Head orthosis therapy in positional plagiocephaly: longitudinal 3D-investigation of long-term outcomes, compared with untreated infants and with a control group.

Background: As there are very few long-term studies on the effects of head orthosis on deformational plagiocephaly (DP), we investigated the outcomes of patients, including facial symmetry and dental occlusion. Methods: Forty-five infants with DP [cranial vault asymmetry index (CVAI) > 3.5 per cent] were divided into two groups: one treated with head orthosis (32 infants) and another without (13 infants). Another group without head asymmetry (CVAI ≤ 3.5 per cent) served as control. Using 3D-stereophotogrammetry, cranial asymmetry was analysed using symmetry-related variables [CVAI, posterior cranial asymmetry index (PCAI), and ear offset]. Data acquisition was performed before (T1) and at the end of treatment (T2), and at the age of 4 years (T3) for the treated group and at T1 and T3 for the remaining groups. Parameters of facial symmetry and dental occlusion were assessed at T3 for infants with DP. Results: Symmetry-related variables (∆T1-T3) improved significantly more in the treated than the control group, whereas these parameters did not differ significantly between the untreated and control group. Comparing the treated and untreated groups between T1 and T3, the reduction in the asymmetry at the treated group was significantly higher for the CVAI and PCAI. In follow-up, the untreated group showed higher incidences of facial asymmetries than the treated group. Seventy-five per cent of all lateral crossbites found in patients with DP were contralateral to the posterior flattening. Limitations: Due to ethical reasons, the investigation is a non-randomized study. Parameters of facial symmetry were only assed for the treated and untreated groups. Conclusion: Head orthosis therapy in patients with DP leads to significantly better long-term outcomes. Facial asymmetries are more frequent in patients with DP who do not receive this treatment.

Does shape affect function? Articulatory skills in babbling of infants with deformational plagiocephaly.

PURPOSE: The purpose of this study was to quantitatively analyse pre-speech/early language skills in healthy full-term infants with moderate or severe deformational plagiocephaly (DP) and in infants without any skull asymmetry. METHODS: At 6 and 12 months, 51 children with DP (41 moderate, 10 severe cases) were studied, along with 15 infants serving as control. Deformational plagiocephaly (DP) was objectively determined based on cranial vault asymmetry (CVA) using 3D stereophotogrammetry (3dMDhead System® and Analytics 4.0, Cranioform®). Articulatory skills in babbling were assessed using the articulatory skill (ART-index) and mean syllable number (MSN). At 12 months, standardized parental questionnaires were used to evaluate early language outcomes. RESULTS: Overall, 3546 vocalizations were studied. Statistical tests did not reveal any significant differences of the ART-index between the three groups (ANOVA, F[2,63] = 0.24, p = 0.24). MSN likewise did not differ between the three shape groups (Kruskal-Wallis, p = 0.84). Among the children assigned to the at-risk group for language outcomes at 12 months were seven members of the symmetrical shape group (vs. seven assigned to the normally developing group), nine of the moderate DP group (vs. 27), and one of the severe DP group (vs. six). Fisher's exact test was used to analyse whether helmet therapy in the moderate DP group affected the results by influencing language outcomes, but did not reveal any significant influence (p = 0.712). CONCLUSIONS: The results of this study do not support arguments suggesting that DP is a cognitive risk condition. The suggestion that a direct neurophysiological relationship exists between a DP condition and a cognitive developmental delay remains controversial.

The prognostic value of GLUT-1 staining in the detection of malignant transformation in oral mucosa.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common tumor entity worldwide. Unfortunately, the multimodal treatment consisting of surgery, radiation, and chemotherapy does not show the desired efficacy. The intent of this study was to evaluate the sensitivity and specificity of an oral brush biopsy in combination with glucose transporter (GLUT)-1 staining in identifying premalignant and malignant lesions. METHODS: A total of 72 patients were included in the study, divided into four diagnostic subgroups (24 healthy, 15 carcinoma, 18 leukoplakia, 15 oral lichen planus). Oral brush biopsies were taken and analyzed for GLUT-1 expression by immunocytologic staining. Incisional biopsy served as the gold standard. RESULTS: Twelve (80 %) of the 15 carcinomas, nine (50 %) of the 18 leukoplakia, nine (60 %) of the 15 oral lichen planus, and none of the healthy specimens stained positive for GLUT-1. This resulted in a sensitivity rate of 80 % and a specificity rate of 68.42 %. Diagnostic accuracy was 70.83 % based on the correct diagnoses in 51 of 72 patients. CONCLUSION: An oral brush biopsy can easily be performed throughout the entire oral cavity, is noninvasive, and shows high sensitivity and specificity rates with conventional cytology or computer-assisted analysis. CLINICAL RELEVANCE: The significance of GLUT-1-specific staining with an oral brush biopsy is more limited than expected but could be used as an additional tool in detecting malignant transformation in the oral cavity.

Perception of children's faces with unilateral coronal synostosis--an eye-tracking investigation.

PURPOSE: Premature unilateral coronal craniosynostosis results in distinctive cranial and facial abnormalities of varying severity, including orbital dystopia and an abnormal head shape. As the face is affected, these children may encounter stigmatization. To avoid this scenario, many parents elect for their child to undergo surgical correction. Laypeople's perception of children with either untreated or treated unilateral coronal craniosynostosis (UCS) has not yet been objectively evaluated. METHODS: This study introduces eye tracking as an objective instrument in order to evaluate the perception of 14 children with coronal synostosis, both pre- and postoperatively. Age-matched healthy children served as a control group. Using standardized photos, the involuntary eye movements and the fixations of 30 unaffected laypeople were evaluated. RESULTS: In the untreated children, whose faces were characterized by striking orbital dystopia, the eyes drew more attention than those of the healthy children. The results of our study demonstrate that the operative correction of unilateral coronal synostosis results in the normalization of the asymmetry of the fronto-orbital region, whereas the C-shaped deformity of the midface, which is not addressed via surgery, subsequently attracts more attention. CONCLUSION: Eye tracking objectively evaluates both the perception of craniofacial abnormalities and the extent of the approximation of normality after surgical correction. We introduce eye tracking as an objective measurement tool for craniofacial abnormalities for the first time.

Erlotinib and gefitinib responsiveness in head and neck cancer cell lines--a comparing analysis with cetuximab.

OBJECTIVE: The objective of this study is to examine the efficacy of erlotinib and gefitinib with respect to epidermal growth factor (EGF) and cetuximab response in head and neck cancer cell lines. MATERIALS AND METHODS: Five human head and neck carcinoma cell lines were treated with EGF, cetuximab, erlotinib, and gefitinib, and the effects were measured with a crystal violet assay. The efficacies of cetuximab, erlotinib, and gefitinib in clinically relevant concentrations were statistically analyzed. The expression of the epidermal growth factor receptor (EGFR) and phosphorylation patterns were detected with fluorescence-activated cell sorting (FACS) analysis and western blot analysis. The endogenous production of EGF by the cells was detected with an enzyme-linked immunosorbent assay. Finally, EGFR, KRAS, BRAF, and PI3K mutation analyses were performed. RESULTS: All of the cell lines had a poor or no response to EGF but exhibited distinct EGFR phosphorylation and EGFR expression. Compared to cetuximab, erlotinib and gefitinib demonstrated a greater impact on the majority of the cell lines. The only cell line that showed a concentration-dependent behavior toward EGF and strong EGFR phosphorylation was entirely resistant to cetuximab, erlotinib, and gefitinib. The production of EGF in all cell lines was very low. Mutational analysis of all cell lines revealed wild-type EGFR, KRAS, BRAF, and PI3K. CONCLUSIONS: The prediction of anti-EGFR treatment cannot be based on responsiveness to EGF or EGFR activation. CLINICAL RELEVANCE: Erlotinib and gefitinib show good response in EGF-independent cell lines and might be useful drugs in tumors that are less responsive to cetuximab.

Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines. METHODS: Five different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot. RESULTS: Incubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination. CONCLUSION: This is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro-apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161. CLINICAL RELEVANCE: SMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy.

Diagnostic features of prematurely fused cranial sutures on plain skull X-rays.

PURPOSE: The characteristic features of prematurely fused craniosynostosis in plain radiographs have already been described in literature, but there is no clinical trial investigating the individual features of every single form of craniosynostosis. We described suture-specific characteristics as well as its frequency of appearance in plain radiographs in every different form of craniosynostosis. Intraoperative findings served as control to confirm the diagnosis. METHODS: One hundred twenty-seven children with prematurely fused cranial sutures who underwent a skull X-ray from 2008 to 2012 were investigated in the present study. In detail, 34 children with frontal, 60 with sagittal, 13 with unilateral and 14 with bilateral coronal synostosis and 3 with unilateral lambdoid craniosynostosis as well as 3 children with a bilateral lambdoid synostosis were included. RESULTS: Typical radiological characteristics in craniosynostosis exist. These features as well as its frequency in craniosynostosis in plain skull radiographs are presented. In all cases, these typical features enabled a correct diagnosis, which was confirmed by intraoperative findings. CONCLUSION: The frequency of the appearance of typical features is listed and may serve as a "mental internal check list" in the radiological approach to craniosynostosis. The study points out the value of plain skull X-rays as it enabled proper diagnosis in all investigated 127 cases.

Intraoperative 3-D imaging improves sentinel lymph node biopsy in oral cancer.

PURPOSE: The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer. METHODS: Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used. RESULTS: All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients. CONCLUSION: FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer.

3D stereophotogrammetric analysis of operative effects after broad median craniectomy in premature sagittal craniosynostosis.

INTRODUCTION: There is ongoing discussion on the diagnostic methods, the need of surgical treatment, and the surgical strategies for premature craniosynostosis. MATERIALS AND METHODS: This study examined the operative procedure of a standardized broad median craniectomy, active tilting of the forehead, and bitemporal greenstick fracturing in children with premature sagittal craniosynostosis. To objectively analyze the direct surgical results, we used a 3D stereophotogrammetry scanner, as previously described. RESULTS: A 3D analysis showed a significant increase in the width, cranial index (CI), head and coronal circumferences, intracranial volume, and cranial base width after surgery. Head length was the only parameter that demonstrated a significant decrease postoperatively. Asymmetry and the 30° diagonal difference showed no significant changes. CONCLUSION: 3D stereophotogrammetry is a reliable and valuable tool with no side effects. It demonstrated that the extended surgical procedure achieves good postoperative results with a reduced length and increased width and, therefore, an improved CI. Additionally, the total intracranial volume was significantly increased after surgery.

Oral health-related quality of life (OHRQoL) and implant therapy: A prospective multicenter study of preoperative, intermediate, and posttreatment assessment.

The purpose of this multicenter continuation study was to use high patient numbers in order to generate reliable statements regarding the association between different implant indications and OHRQoL. Patients with various types of indication for dental implants, ranging from single tooth loss to edentulous jaws, were included. Quality of life relating to dental implants was assessed through the oral health impact profile (OHIP-G-21), which has a summary score from 0 to 20 in healthy patients. In total, 16 253 patients from 29 centers (European Centers for Dental Implantology (ECDI)) were involved in the study between 2009 and 2021.8251 patients (50.7%) completed the questionnaire after implant insertion, and 4996 patients (30.7%) after prosthodontic treatment. The average age was 54 years (range 18-88 years). Posterior single-tooth gap (28.5%) and free-end gap (27.8%) were the most frequent indications. The preoperative OHIP-G-21 score for all patients was 32.81 (SD 11.92), while the score during the healing period was 30.00 (SD 10.72), and after completion of treatment 27.24 (SD 9.26) (p < 0.001). The most significant improvements in OHIP-G-21 scores were in the indication of edentulous jaw (phase 1, 41.81 (SD 15.53); phase 2, 35.39 (SD 14.22); phase 3, 29.60 (SD 10.12) (p < 0.001). The study revealed significant improvements in the most frequently reported problems (chewing, serious concerns, appearance) (p < 0.001). Insertion of dental implants and prosthodontic rehabilitation led to an improved OHRQoL for patients with all indications for dental implants. Special attention should be paid to patients with edentulous jaw, since in comparison with other indications it had the greatest impact on improving OHRQoL. The psychological dissatisfaction scale of the OHIP-G-21 represented the most important factors for patients, and these scores were substantially influenced by implant therapy. Thus, treating physicians should increase their focus on these factors, in order to avoid dissatisfaction and increase the likelihood of complete implant therapy success.