Photogrammetric evaluation of corrective surgery for trigonocephaly.

The aim of this study was to capture preoperative, postoperative, and follow-up head shapes of male trigonocephaly patients who underwent fronto-orbital remodelling (FOR), using three-dimensional (3D) photography. Fifty-seven male infants with metopic synostosis operated on using standardized FOR during a 5-year period were included. All measurements were compared with those of an age-matched healthy control cohort (n = 253 for early postoperative comparison, n = 43 for the 1-year follow-up comparison) to determine the effect of FOR at 14 days and at 1 year post-surgery. Intracranial volume, frontal angle, nasofrontal angle, interfrontoparietal-interparietal ratio, and inter-orbital distances were measured 1 day preoperatively, 14 days and 1 year postoperatively. Mean age at surgery was 9.7 ± 1.1 months. Prior to surgery, boys with metopic synostosis showed a reduced intracranial volume (-7.0%, P < 0.001), frontal angle (-10.2%, P < 0.001), interfrontoparietal-interparietal ratio (-4.9%, P < 0.01), and orbital distances (-6.5%, P < 0.001) compared to the reference group, but values did not differ significantly from the specific control group after surgery (all P> 0.05). This was consistent by the time of the follow-up examination. Corrective surgery should therefore aim to achieve volume expansion and correction of the deformity. Furthermore, 3D photogrammetry provides a valuable alternative to computed tomography scans in the diagnosis of metopic synostosis, significantly reducing the amount of radiation exposure to the brain.

Neck involvement and disease recurrence in adenoid cystic carcinoma of the minor salivary glands: the role of surgery in primary and progressive disease.

The aim of this study was to analyse the rates of metastatic events and clinical outcomes of patients with adenoid cystic carcinoma (ACC) of the minor salivary glands and to critically evaluate the role of surgical therapy. A retrospective cohort study was designed including all patients with ACC of the oral minor salivary glands treated in the study department during the years 2010-2017. Relevant clinicopathological data were analysed to determine factors with an impact on overall survival (OS) and progression-free survival (PFS). Forty-one patients with primary ACC of the oral cavity and the oropharynx were included. Cervical metastases were found in 14 patients (34.1%) and were shown to have a significant negative impact on OS (P=0.009) and PFS (P=0.03). Sixteen patients developed disease recurrence during follow-up (39.0%) and most patients exhibited local disease recurrence with or without regional or distant metastases (14/16, 87.5%). Local recurrence was treated successfully with surgery in five cases. We recommend surgical therapy for patients with ACC of the minor salivary glands, including elective neck dissection and microvascular reconstruction, to optimize the planning of adjuvant therapy.

Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers.

PURPOSE: Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) have been associated with the aggressive nature of head and neck cancers (HNCs). These tumours grow diffusely, leading to extremely challenging differentiation between tumour and healthy tissue. This analysis aims to introduce a novel approach of tumour detection, contouring and targeted radiotherapy of HNCs using visualisation of CAFs: PET-CT with 68Ga-radiolabeled inhibitors of FAP (FAPI). METHODS: FAPI PET-CT was performed without complications prior to radiotherapy in addition to contrast enhanced CT (CE-CT) and MRI on 14 patients with HNC. First, for tissue biodistribution analysis, volumes of interest were defined to quantify SUVmean and SUVmax in tumour and healthy parenchyma. Secondly, using four thresholds of three-, five-, seven- and tenfold increase of FAPI enhancement in the tumour as compared with normal tissue, four different gross tumour volumes (FAPI-GTV) were created automatically. These were compared with GTVs created conventionally with CE-CT and MRI (CT-GTV). RESULTS: The biodistribution analysis revealed high FAPI avidity within tumorous lesions (e.g. primary tumours, SUVmax 14.62 ± 4.44; SUVmean 7.41 ± 2.39). In contrast, low background uptake was measured in healthy tissues of the head and neck region (e.g. salivary glands: SUVmax 1.76 ± 0.31; SUVmean 1.23 ± 0.28). Considering radiation planning, CT-GTV was of 27.3 ml, whereas contouring with FAPI resulted in significantly different GTVs of 67.7 ml (FAPI × 3, p = 0.0134), 22.1 ml (FAPI × 5, p = 0.0419), 7.6 ml (FAPI × 7, p = 0.0001) and 2.3 ml (FAPI × 10, p = 0.0001). Taking these significant disparities between the GTVs into consideration, we merged FAPI-GTVs with CT-GTVs. This resulted in median volumes, that were, as compared to CT-GTVs, significantly larger with FAPI × 3 (54.7 ml, + 200.5% relative increase, p = 0.0005) and FAPI × 5 (15.0 ml, + 54.9%, p = 0.0122). Furthermore, FAPI-GTVs were not covered by CE-CT-based planning target volumes (CT-PTVs) in several cases. CONCLUSION: We present first evidence of diagnostic and therapeutic potential of FAPI ligands in head and neck cancer. Larger studies with histopathological correlation are required to validate our findings.

The prognostic significance of the lymph node ratio in oral cancer differs for anatomical subsites.

The aim of this study was to validate the prognostic significance of the lymph node ratio (LNR) in patients suffering from oral squamous cell carcinoma in regard to different anatomical subsites. A cohort of 430 patients was investigated to determine the rates of primary metastasis and local and regional disease recurrence. Correlation analysis of the LNR with relevant clinical and pathological parameters was performed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the prognostic impact for different subsites. Significantly differing rates of primary metastasis and loco-regional disease recurrence were found for cancer of different anatomical subsites of the head and neck. Furthermore, ROC curve analysis suggested that LNR has prognostic relevance in subsets of cancer (tongue, P< 0.001; alveolar process, P= 0.04; maxilla, P= 0.03; buccal mucosa, P= 0.02). The LNR of cancer located in the soft palate (P= 0.6) and floor of the mouth (P= 0.11) showed little or no association with the clinical outcome. There is the need for a more sensitive consideration of the LNR as a factor in the assessment of risk and the treatment decision, as the anatomical subsite plays a crucial role in its impact on the clinical outcome.

Relations between mandible-only advancement surgery, the extent of the posterior airway space, and the position of the hyoid bone in Class II patients: a three-dimensional analysis.

The objective of the present study was to evaluate the relation between mandibular advancement, the three-dimensional extent of the posterior airway space (PAS), and the position of the hyoid bone, using cone-beam computed tomography (CT). Twenty-eight Class II patients (21 women (mean (SD) age 29 (9) years) and seven men (mean (SD) age 23 (6) years)), who had had mandibular-only advancement surgery (Obwegeser-Dal Pont) were included in the study. In each case, cone-beam CT scans were taken one week before and six months after operation, and a retrospective analysis made of the alterations of several airway variables (volume, mean cross-sectional area, and diameter) and the three-dimensional extent of mandibular and hyoid movement, by using IPlan® cranial software. A linear regression was also done to correlate mandibular advancement, the movement of the hyoid bone, and airway variables. There were significant postoperative increases in all volumetric PAS variables, and in most diametric and spherical variables (p<0.05). There was also a significant linear relation between forward displacement of the mandible and the movement of the hyoid bone (p<0.05). These results show that mandible-only advancement surgery causes an increase in most dimensions of the PAS. This intervention can be assumed to reduce airway resistance and therefore might be a suitable treatment option for patients with obstructive sleep apnoea syndrome.

Long-term donor site morbidity in head and neck cancer patients and its impact on quality of life: a cross-sectional study.

Modern head and neck reconstructive surgery offers a multitude of different reconstructive options. In such cases, donor site morbidity is an important factor in the affected patient's decision-making. The aim of this study was to perform an objective comparison of donor site morbidity for the five most frequent microvascular donor sites in head and neck reconstructive surgery (radial forearm, anterolateral thigh, fibula, iliac crest, and scapula) using a uniform testing system. In this cross-sectional study, 117 donor sites were analyzed (106 for malignant disease and 11 for non-malignant disease): 73 radial forearm, 14 scapula, 12 anterolateral thigh, 10 fibula, and eight iliac crest. Testing consisted of range of motion, muscle strength, and sensation. The non-affected side served as the control. Quality of life was assessed using the Washington Quality of Life Questionnaire version 4 in its German translation. Range of motion was restricted in 15 cases (12.8%). Muscle strength was decreased in 58 cases (49.6%). Sensation was reduced in 70 cases (60%). Concerning quality of life, 31.2% of patients were limited in their daily activities. The scapula flap showed the highest incidence of overall donor site morbidity. However, correlation between objective and subjective donor site impairment was weak and the majority of patients experienced only minor limitations.

Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study.

Recent studies have indicated that bone shows auto-fluorescence under an appropriate fluorescence lamp. The aim of this preliminary study was to compare the success rates of the established tetracycline fluorescence-guided bone surgery with auto-fluorescence-guided bone surgery in the treatment of medication-related osteonecrosis of the jaw (MRONJ). Forty patients suffering from MRONJ were referred for surgical treatment and were divided randomly into two groups: auto-fluorescence (n=20) or tetracycline fluorescence (n=20) guided bone surgery. The primary endpoint was treatment success, defined as the absence of exposed bone at 8 weeks after surgery. Secondary outcomes assessed were mucosal integrity, signs of infection, pain, and loss of sensitivity; these were evaluated descriptively at 10 days, 8 weeks, 6 months, and 1 year after surgery. At 8 weeks postoperative, 18/20 patients (90%) in the auto-fluorescence group and 17/20 patients (85%) in the tetracycline fluorescence group showed mucosal integrity (P>0.05). At the last follow-up, 94% in the auto-fluorescence group and 89% in the tetracycline fluorescence group presented complete mucosal coverage with no exposed bone, infection, or pain (P>0.05). There was no significant difference between the two techniques for any of the secondary outcomes (P>0.05). The results of this preliminary study show that auto-fluorescence-guided bone surgery has comparable success rates to the established tetracycline fluorescence-guided bone surgery.

Intracranial volume (ICV) in isolated sagittal craniosynostosis measured by 3D photocephalometry: A new perspective on a controversial issue.

BACKGROUND: There are still controversies regarding the intracranial volumes in patients with isolated sagittal craniosynostosis compared to a healthy population. This study aimed to compare the intracranial volume of children with sagittal synostosis and scaphocephaly to an age- and gender-matched control cohort using three-dimensional (3D) photogrammetry. METHODS: 62 boys and nine girls with sagittal craniosynostosis were included in this study. The intracranial volume was measured at the first clinical presentation. However, 3D photogrammetry was performed at children not younger than 3 months. The 3D photogrammetric data of 547 healthy boys and 287 healthy girls between the ages of 3-10 month was analyzed to establish an age- and gender-matched control group. RESULTS: Male patients with sagittal synostosis showed a significantly reduced intracranial volume compared to the reference group. For female patients, the intracranial volume was slightly lower compared to the norm group, but not significantly. CONCLUSIONS: Male children with sagittal synostosis showed significantly decreased intracranial volume between the age of 3 and 10 months compared to an age- and gender-matched control group. Female patients in the same age group presented a lower intracranial volume compared to the norm group. Measuring intracranial volume using 3D photogrammetry is a comparable and valuable alternative to CT scans that leads to a significant reduction of radiation exposure to the growing brain.

The value of three-dimensional printing modelling for surgical correction of orbital hypertelorism.

Orbital hypertelorism is defined as an increased distance between both medial and lateral sides of the orbits. Most common causes are frontonasal malformations, craniofacial fissures, encephalocele and a miscellaneous group of various syndromic or chromosomal disorders. Surgical correction of orbital hypertelorism is still challenging. The present report describes a case of severe orbital hypertelorism of an 11-year-old boy, where surgical correction was planned using three-dimensional printing modelling. This approach allowed reducing time of surgery, accurately planning the location of the osteotomies and precontouring the osteosynthesis material. Three-dimensional models are very helpful tools in planning complex craniofacial operative procedures.

Long-term incidence of sensory disturbance in the forehead after fronto-orbital advancement in isolated nonsyndromic craniosynostosis.

In the majority of the craniofacial literature, preservation of the supraorbital nerve during fronto-orbital advancement (FOA) is recommended. However, only a few studies have evaluated the incidence of sensory disturbance in the forehead after FOA during long-term follow-up. 57 children who underwent FOA in their first year of life because of isolated nonsyndromic craniosynostosis including trigonocephaly, anterior plagiocephaly or oxycephaly, were evaluated for sensory disturbance in the frontal region with a minimum follow-up of 27 months. An objective and repeatable measurement using the Semmes-Weinstein test was possible in 36 children older than 5 years at last follow-up. We revealed no sensory deficits in all patients, even in 3 patients, where one of the supraorbital nerves was transected during FOA. As previous reports have suggested a full recovery of sensation after transection of the supraorbital nerve during FOA I seen, the need to preserve the nerve has to be evaluated. However, as release of the nerve from the supraorbital rim is possible, we generally recommend preserving this structure, to minimize the risk of sensory deficits in the forehead region.

Long-term results in nonsyndromatic unilateral coronal synostosis treated with fronto-orbital advancement.

Children with unilateral isolated coronal suture synostosis suffer from frontal plagiocephaly. In this retrospective study we analyzed 21 patients who were treated with an identical and standardized surgical technique of fronto-orbital advancement with hypercorrection with an average follow-up of 57.5 months. The median age at surgery was 12.1 months. The median average amount of blood loss during the operation was less than 188 ml. Not a single major complication was observed. According to the classification of Whitaker, 15 patients had a Class 1 outcome, with excellent surgical results. Three patients were defined as Class 2 outcome. One of our patients was Class 3 and two patients were Class 4 because of severe forehead retrusion and temporal hollowing. Re-operation rate was 14.3%. 67% of our patients showed a correction or an improvement of the typical C-shaped deformity in their follow-up examination. Aesthetic outcomes were excellent in 13, good in 5, and poor in 3 of cases, as judged by their families and the craniofacial team. Unilateral coronal synostosis can be successfully treated by fronto-orbital advancement with a low complication rate and an excellent clinical outcome. To minimize the need of re-operations, fronto-orbital advancement should be performed with an overcorrection on the affected side.

TGF-ß and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers.

Transforming growth factor-beta (TGF-ß) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-ß signaling enhances de novo tumor development, whereas TGF-ß overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-ß-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-κB (NF-κB), a transcription factor, which promotes malignant progression in HNSCC. However, what role cross-talk between components of the TGF-ß and NF-κB pathways plays in altered activation of these pathways has not been established. Here, we show TGF-ß receptor II and TGF-ß-activated kinase 1 (TAK1) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF-κB family member RELA (p65). Further, TGF-ß1 treatment induced sequential phosphorylation of TAK1, IKK, IκBα and RELA in human HNSCC lines. TAK1 enhances TGF-ß-induced NF-κB activation, as TAK1 siRNA knockdown decreased TGF-ß1-induced phosphorylation of IKK, IκB and RELA, degradation of IκBα, RELA nuclear translocation and DNA binding, and NF-κB-induced reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti-inflammatory compound used in traditional Chinese medicine, also decreased TGF-ß1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-ß1- and tumor necrosis factor-alpha (TNF-α)-induced NF-κB reporter gene activity. Celastrol also inhibited cell proliferation, while increasing sub-G0 DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-ß and RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially suppressed TGF-ß-induced SMAD and NF-κB reporters when compared with constitutive or TNF-α-induced NF-κB reporter gene activation. Thus, cross-talk by TGF-ß via TAK1 and NF-κB promotes the malignant phenotype of HNSCC. Moreover, NF-κB may contribute to the downstream attenuation of canonical TGF-ß signaling through increased SMAD7 expression. Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-ß-NF-κB signal pathway.

Chiari malformation in nonsyndromal single craniosynostosis--much ado about nothing?

BACKGROUND: The significance of Chiari malformation in nonsyndromal-isolated craniosynostosis is still not well documented. Hence, in the present study we investigated the incidence of Chiari malformation in a larger series of patients with nonsyndromic-isolated single-suture craniosynostosis over a 9-year period using preoperative magnetic resonance imaging (MRI). METHODS: Of 215 children who had undergone surgery for nonsyndromic-isolated craniosynostosis, 89 cases (41.4 %) had MRI prior to surgery. All MRIs were screened for Chiari malformation. RESULTS: Only one patient (1.1 %) with isolated lambdoid synostosis showed Chiari malformation preoperatively, which was defined as a cerebellar tonsillar descent greater than 5 mm below the foramen magnum. However, no clinical symptoms were associated with Chiari malformation in this patient. CONCLUSIONS: As Chiari malformation is more likely to be associated with syndromic craniosynostosis, nonsyndromic bilateral coronal synostosis, or synostosis of the lambdoid suture, a general use of MRI as a screening tool for Chiari malformation should not be recommended for patients with nonsyndromic-isolated craniosynostosis who lack clinical symptoms.

Subtotal cranial vault remodelling in anterior sagittal suture closure: impact of age on surgical outcome.

Isolated fusion of the sagittal suture is usually treated before 1 year of age, but some patients present at a later age. The aim of this study was to evaluate the impact of children's age on the surgical outcome. The authors investigated 46 patients with isolated nonsyndromic sagittal craniosynostosis limited to the anterior two-thirds of the cranial vault. All patients underwent subtotal cranial vault remodelling, 36 patients (78.3%) before the age of 12 months (mean 8.92 months) and 10 patients after the age of 12 months (mean 15.77 months). Perioperative parameters and measurements of the cephalic index, preoperatively and postoperatively, were evaluated. All 46 patients showed improved head shape independent of their age. In patients younger than 12 months, mean cephalic indices improved from 65.99 to 74.49 (p<0.0001) and in patients older than 12 months from 66.38 to 74.38 (p<0.0004). There were no statistical differences in perioperative parameters including length of surgery, intraoperative blood loss and duration of hospital stay. In this study, patients showed no significant differences in surgical outcome that could have been related to the age at surgery. Surgical treatment should be performed early enough to benefit from the remodelling potential of the skull.

Ki-67 expression predicts radiosensitivity in oral squamous cell carcinoma.

The prognostic relevance of Ki-67 expression in oral squamous cell carcinoma (OSCC) is still controversial. As proliferating cells are more susceptible to ionizing radiation, the authors investigated if a high proliferation rate reflected by Ki-67 expression, predicts radiosensitivity in OSCC patients. In 52 patients with OSCC who received primary surgery followed by radiation therapy, the proliferation rate was assessed by Ki-67 immunhistochemistry and correlated to recurrent free survival and overall survival. Low proliferative carcinomas showed a significantly shorter mean time to recurrence of 27.5 months compared to 49.5 months of high proliferative tumours (p=0.048). The 5-year survival rate of low proliferative tumours was 49% compared to 80% for high proliferative tumours (p=0.042). This study indicates that tumours with high proliferative activity are more susceptible to radiation therapy. Ki-67 might be used as a marker to predict the response to radiation therapy in patients with OSCC.

Surgical outcome after using a modified technique of the pi-procedure for posterior sagittal suture closure.

Fusion of the sagittal suture is the most prevalent form of craniosynostosis. Due to the variety of deformities of scaphocephaly depending on the location of the fused sagittal suture, the surgical procedure has to be adjusted to the individual case. In this study, 38 patients with a predominantly posterior sagittal suture closure were treated with a modified technique of the pi-procedure and the surgical outcome has been evaluated with respect to complications, morphological and aesthetic outcome. The improvement of the cephalic index in our series in the follow-up examination (mean 60.1 months) after surgery was significant (p<0.0001). According to the classification of Whitaker, 31 patients had a Class 1 outcome, with excellent surgical results. Aesthetic outcomes were excellent in 29, good in 5, and poor in 4 of cases, as judged by both the families and the craniofacial team. No severe complications have been observed. Posterior sagittal suture with marked occipital bulging can be successfully treated with this modified posterior procedure with a low complication rate, significant improvement of the cephalic index and a good aesthetic outcome. In all cases of sagittal synostosis, the operative procedure should be tailored to the nature and severity of the deformity.