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.

Successful microvascular surgery in patients with thrombophilia in head and neck surgery: a case series.

BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.

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.

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.

A liquid chromatography-tandem mass spectrometry method for the quantification of ampicillin/sulbactam and clindamycin in jawbone, plasma, and platelet-rich fibrin: Application to patients with osteonecrosis of the jaw.

Ampicillin in combination with sulbactam is a widely used drug choice for infection prophylaxis, especially in oral and maxillofacial surgery. Clindamycin serves as an alternative in patients with known allergy to ß-lactam antibiotics. To ensure effective prophylaxis, it is important to achieve sufficiently high concentrations of active antibiotic substances in the tissues affected by the surgery. To this end, a LC-MS/MS method was developed and validated that allows the quantification of ampicillin, sulbactam and clindamycin in jawbone, plasma, and so-called platelet-rich fibrin (PRF). Validation was performed in accordance with the European Medicines Agency guidelines for bioanalytical method validation. For all matrices, sample processing was carried out by protein precipitation with acetonitrile or methanol 80%, containing the isotope labelled internal standards (IS) of the three drugs. Analytes were separated on a pentaflourophenyl column at 20 °C using gradient elution. Furthermore, detection was accomplished by electrospray ionisation in positive-ion mode (ampicillin, clindamycin and corresponding IS) and negative-ion mode (sulbactam and corresponding IS) in combination with multiple reaction monitoring. Depending on the analyte and the matrix under investigation, calibration curves ranged from 0.14 to 59.8 µg/g (jawbone - ampicillin), 2.0-1000 µg/mL (plasma - ampicillin), and 1.0-495 µg/mL (PRF - ampicillin). All analytes fulfilled the requirements of the guideline regarding sensitivity, linearity, selectivity, carryover, within-run and between run accuracy and precision, matrix effect and extraction recovery in all matrices. The method was successfully applied to measure concentrations of ampicillin, sulbactam and clindamycin in real-life samples obtained in routine clinical practice.

Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly.

Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.

Bone Concentration of Ampicillin/Sulbactam: A Pilot Study in Patients with Osteonecrosis of the Jaw.

Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.

[18F]FDG-PET/CT improves the detection of synchronous malignancies at primary staging of oral squamous cell carcinoma - A retrospective study.

The purpose of this study was to show the non-inferiority of [18F]FDG-PET/CT compared with panendoscopy with regards to secondary malignancies of the UADT, and to evaluate the diagnostic performance of PET/CT for detecting synchronous malignancies. Patients with newly diagnosed OSCC and both panendoscopy and [18F]FDG-PET/CT at primary staging were enrolled in this retrospective study. The accuracy in detecting synchronous malignancies was assessed for both modalities, and their diagnostic measures for the detection of malignancies within the UADT were compared. Histopathological analysis and clinical follow-up served as reference standards. In total, 182 patients were enrolled in this study. Eighteen patients (9.9%) had in total 22 synchronous malignancies, of which eight were located within the UADT. [18F]FDG-PET/CT detected all malignancies within the whole body (sensitivity: 100%) and yielded false-positive results in four cases (specificity: 97.6%). Sensitivity ([18F]FDG-PET/CT: 100% vs panendoscopy: 87.5%), specificity (99.4% vs 100%), negative predictive value (100% vs 99.4%), and positive predictive value (88.9% vs 100%) for detecting secondary UADT malignancies did not differ between modalities (all p = 0.32). Within the limitations of the study it seems that [18F]FDG-PET/CT detects synchronous malignancies of the UADT with an accuracy comparable to panendoscopy, and enables highly sensitive whole-body tumor screening in patients with newly diagnosed OSCC. This could be a relevant factor for therapeutic decision making in clinical routine.

Free Skin Grafting to Reconstruct Donor Sites after Radial Forearm Flap Harvesting: A Prospective Study with Platelet-Rich Fibrin (PRF).

Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44% versus 86.96% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts.

Low Energy Status under Methionine Restriction Is Essentially Independent of Proliferation or Cell Contact Inhibition.

Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.

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.

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.

Mammary analogue secretory carcinoma of a salivary gland of the hard palate with contralateral cervical lymph node metastases: A case report.

Mammary analogue secretory carcinoma (MASC) is a rare malignant tumour of the salivary glands, with only few cases reported in the literature to date. Initial preoperative staging is crucial for all patients with an oral malignancy to visualize the tumour, detect lymph node or distant metastases and plan therapeutic interventions. In the case presented herein, radiological imaging revealed a tumour of the right hard palate with suspected positive contralateral lymph nodes. Therefore, local tumour resection comprising hemimaxillectomy and bilateral neck dissection was performed. The diagnosis of MASC was finally based on characteristic histopathological and immunohistochemical findings, such as S100 protein and mammaglobin positivity. The diagnosis of MASC may be challenging, as such findings lack specificity. To confirm the diagnosis, molecular genetic examinations may be performed to detect a highly specific ETV6-NTRK3 fusion gene. Depending on the results of these examinations, surgery, alone or combined with adjuvant radiation or chemoradiation, is the recommended approach. In summary, MASC should be treated similarly to other low-grade salivary gland tumours, such as acinic cell carcinoma, as they exhibit biological and histopathological similarities.

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.

Accuracy of 18-F Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Imaging in Primary Staging of Squamous Cell Carcinoma of the Oral Cavity.

Importance: Squamous cell carcinoma (SCC) of the oral cavity is one of the most common tumor entities worldwide. Precise initial staging is necessary to determine a diagnosis, treatment, and prognosis. Objective: To examine the diagnostic accuracy of preoperative 18-F fluorodeoxyglucose (FDG) positron emission tomographic/computed tomographic (PET/CT) imaging in detecting cervical lymph node metastases. Design, Setting, and Participants: This prospective diagnostic study was performed at a single tertiary reference center between June 1, 2013, and January 31, 2016. Data were analyzed from April 7, 2018, through May 31, 2019. Observers of the FDG PET/CT imaging were blinded to patients' tumor stage. A total of 150 treatment-naive patients with clinical suspicion of SCC of the oral cavity were enrolled. Exposures: All patients underwent FDG PET/CT imaging before local tumor resection with selective or complete neck dissection. Main Outcomes and Measures: The accuracy of FDG PET/CT in localizing primary tumor, lymph node, and distant metastases was tested. Histopathologic characteristics of the tissue samples served as the standard of reference. Results: Of the 150 patients enrolled, 135 patients (74 [54.8%] men) with a median age of 63 years (range, 23-88 years) met the inclusion criteria (histopathologically confirmed primary SCC of the oral cavity/level-based histopathologic assessment of the resected lymph nodes). Thirty-six patients (26.7%) in the study cohort had neck metastases. Use of FDG PET/CT detected cervical lymph node metastasis with 83.3% sensitivity (95% CI, 71.2%-95.5%) and 84.8% specificity (95% CI, 77.8%-91.9%) and had a negative predictive value of 93.3% (95% CI, 88.2%-98.5%). The specificity was higher than for contrast-enhanced cervical CT imaging (67.0%; 95% CI, 57.4%-76.7%; P < .01) and cervical magnetic resonance imaging (62.6%; 95% CI, 52.7%-72.6%; P < .001). Ipsilateral lymph node metastasis in left- or right-sided primary tumor sites was detected with 78.6% sensitivity (95% CI, 63.4%-93.8%) and 83.1% specificity (95% CI, 75.1%-91.2%), and contralateral metastatic involvement was detected with 66.7% sensitivity (95% CI, 28.9%-100.0%) and 98.6% specificity (95% CI, 95.9%-100.0%). No distant metastases were observed. Conclusions and Relevance: In this study, FDG PET/CT imaging had a high negative predictive value in detecting cervical lymph node metastasis in patients with newly diagnosed, treatment-naive SCC of the oral cavity. Routine clinical use of FDG PET/CT might lead to a substantial reduction of treatment-related morbidity in most patients.

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.

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.

Sensitization of head and neck squamous cell carcinoma to apoptosis by combinational SMAC mimetic and Fas ligand-Fc treatment in vitro.

This study aimed to investigate the in vitro efficacy of three different SMAC mimetics for pro-apoptotic sensitization of HNSCC cells. We evaluated BV-6 in comparison to Birinapant and LCL161, for which pro-apoptotic sensitization effects have been demonstrated. Concentration-dependent response was measured for BV-6 in each cell line with an average IC50 value 8-fold lower than of aforementioned SMAC mimetics. Combination treatment of FasL (log2) and BV-6 (IC10) showed highly significant cell count reductions even in the lowest applied concentration in five cell lines (PCI-1: p = 0.0002, PCI-13: p = 0.0002, Detroit 562: p: p < 0.0001, FaDu: p < 0.0001, SCC-25: p = 0.0047). Synergistic effects (y < 1) were evident in eight out of 10 cell lines (PCI-1, PCI-9, PCI-13, PCI-68, Detroit 562, FaDu, SCC-25 and HaCaT). Annexin V assays revealed in nine cell lines very highly significant (p < 0.001) pro-apoptotic effects of BV-6. Western blots showed a heterogeneous IAP expression following SMAC mimetic treatment. Except for two cell lines, at least the cellular inhibitor of apoptosis protein 1 (cIAP1) was degraded in response to BV-6. For prospective targeted HNSCC therapy, this study identifies SMAC mimetics, particularly BV-6 as the compound with the highest pro-apoptotic potency, as promising antitumor agents.

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.