ASA score and procedure type predict complications and costs in maxillofacial reconstructive surgery: a retrospective study using a hospital administrative database.

BACKGROUND: Reconstruction of osseous and soft tissue defects after surgical resection of oral cavity cancers can be achieved by a single-stage procedure with a microvascular bone flap or by a two-step approach with a soft tissue flap and subsequent bone augmentation. The therapeutic approach should be selected based on the patient’s needs. Economic pressure requires preoperative risk assessment and estimation of the postoperative course. Flat-rate reimbursement systems via diagnosis-related groups with insufficient morbidity adjustments and financial sanction of medical complications might additionally cause false incentives in the choice of treatment. OBJECTIVE: This study aimed to assess the influence of the type of flap chosen for maxillofacial reconstructive surgery on the total costs. Complication rates of different types of flap surgery and their prediction by a preoperative risk assessment tool (American Society of Anesthesiologists [ASA] score) were determined. Overall, the fairness of the current reimbursement system was rated. METHODS: Patient characteristics, clinical data, and data on total costs and reimbursement of patients aged 18 years and older having undergone maxillofacial reconstructive flap surgery at the University Hospital of Zurich (Switzerland) between 2012 and 2014 were analysed. The preoperative risk was classified by the ASA score. Complications were graded according to the Clavien-Dindo classification system and the comprehensive complication index (CCI). Statistical analysis included Spearman and Pearson rank correlation, Kruskal-Wallis and Mann-Whitney nonparametric tests, and linear regression analysis. RESULTS: 129 patients were included in this study. Soft tissue flaps were performed in 82 patients, of which 56 were radial forearm flaps (43.4%), bone flaps in 41 patients, of which 32 were fibula flaps (24.8%), and combined flaps in 6 patients (4.7%). Patients with fibula flaps showed a significantly higher CCI and higher total costs. Higher preoperative ASA scores were significantly associated with increased length of stay, total costs and complications. Both the ASA score and reconstruction with a radial forearm flap were significant predictors of complications and total costs. Total median costs for radial forearm flaps were CHF 50,560 (reimbursement: CHF 60,851; difference: CHF 10,291) and for fibula flaps CHF 66,982 (reimbursement: CHF 58,218; difference: CHF −8,764). CONCLUSION: The ASA score allows a reliable preoperative assessment of patient outcomes and financial burden in maxillofacial reconstructive flap surgery. The type of flap reconstruction significantly influences complications and ultimately total costs. The current reimbursement system via diagnosis-related groups (DRGs) does not take sufficient account of this fact. Adaptations are therefore needed to prevent misplaced incentives to the detriment of patients.

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm2, A3: 194 ± 10 cm/cm2, B2: 249 ± 19 cm/cm2, B3: 264 ± 17 cm/cm2) when compared with controls (A1: 129 ± 10 cm/cm2, B1: 185 ± 8 cm/cm2). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

Antimicrobial peptide gene expression in medication-related osteonecrosis of the jaw.

Bisphosphonates and denosumab are commonly used antiresorptive therapies in patients with bone metastasis and osteoporosis. Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of these drugs, and infection has been recognized as a contributing factor. Current therapeutic options for MRONJ show limited effectiveness, therefore necessitating novel treatment strategies. Bisphosphonates have recently been reported to induce the expression of antimicrobial peptides (AMPs), an inherent component of the immune system. Therefore, the aim of the present study was to investigate and compare the influence of the anti-RANKL antibody denosumab and bisphosphonates on the gene expression of selected AMPs: human α-defensin-1, human α-defensin-3, human ß-defensin-1, and human ß-defensin-3. Bone specimens were collected from patients with MRONJ who had been treated with bisphosphonates (n = 6) or denosumab (n = 6), and from healthy subjects (n = 6) with no history of treatment with bone metabolism-influencing drugs. Reverse transcription-quantitative polymerase chain reaction was used to quantify the expression levels of selected AMPs. Samples from patients treated with denosumab showed significantly higher mRNA expression of human α-defensin-3 and human ß-defensin-3 than those from healthy subjects. This finding is similar to previously described upregulated expression of human defensins in patients with MRONJ after bisphosphonates treatment. This suggests that the elevated expression of defensins may be at least a part of the mechanism underlying the pathogenesis of osteonecrosis induced by antiresorptive therapies, which can serve as a new target for potential treatment of MRONJ.

Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype.

INTRODUCTION: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a widely used imaging tool for oral squamous cell carcinoma (OSCC). Preliminary studies indicate that quantification of tumor metabolic uptake may correlate with tumor hypoxia and aggressive phenotypes. METHODS: Retrospective review of a consecutive cohort of OSCC (n = 98) with available pretherapeutic FDG-PET/CT, treated at the University Hospital Zurich. Clinico-pathologico-radiological correlation between maximum standard uptake value (SUVmax) of the primary tumor, immunohistochemical staining for hypoxia-related proteins glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1-alpha (HIF1a), depth of invasion (DOI), lymph node metastasis, and outcome was examined. RESULTS: Positive staining for GLUT1 and HIF1a on immunohistopathological analysis correlated with increased SUVmax on pretherapeutic imaging and with increased DOI (Kruskal-Wallis, P = 0.037, and P = 0.008, respectively). SUVmax and DOI showed a strong positive correlation (Spearman Rho, correlation coefficient = 0.451, P = 0.0003). An increase in SUVmax predicted nodal metastasis (Kruskal-Wallis, P = 0.017) and poor local control (log rank, P = 0.047). CONCLUSION: In OSCC, FDG-PET-derived metabolic tumor parameter SUVmax serves as a surrogate marker for hypoxia and can be used to predict tumor aggressiveness, with more invasive phenotypes and poorer local control.

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23.

The authors would like to make a correction to their published paper [1][...].

Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma.

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning.

[CAD/CAM Revolution in Craniofacial Reconstruction]. / Die CAD/CAM-Revolution in der kraniofazialen Rekonstruktion.

CAD/CAM Revolution in Craniofacial Reconstruction Abstract. The face is an important part of the personality and at the same time fulfils a variety of tasks. Aesthetics and function form a unique unit. The formation of the field of oral and maxillofacial surgery began in the first decades of the last century. It includes the prevention, diagnosis, therapy and rehabilitation of diseases, injuries, malformations and changes of the complex structures of the face, oral cavity, jaw and teeth. In the meantime, oral and maxillofacial surgery has arrived in the 21st century. Today's oral and maxillofacial surgery is a link between medicine and dentistry and a protagonist in the implementation of digital workflows in clinical care. Individual solutions with patient-specific implants are the rule, computer-assisted techniques support the surgeon in the planning and performing of surgical procedures. This article intends to give you an insight into how our patients benefit from advanced technologies.

Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients.

AIMS: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of circulating immune cells (peripheral blood mononuclear cells, PBMCs) of early onset MI patients. One lncRNA significantly suppressed in post-MI patients was further investigated in a murine knockout model. METHODS AND RESULTS: Individual RNA-sequencing (RNA-seq) was conducted on PBMCs from 28 post-MI patients with a history of MI at age ≤50 years and stable disease ≥3 months before study participation, and from 31 healthy individuals without manifest cardiovascular disease or family history of MI as controls. RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI PBMCs, among which nuclear enriched abundant transcript (NEAT1) was the most highly expressed lncRNA, and the only one significantly suppressed in patients. Multivariate statistical analysis of validation cohorts of 106 post-MI patients and 85 controls indicated that the PBMC NEAT1 levels were influenced (P = 0.001) by post-MI status independent of statin intake, left ventricular ejection fraction, low-density lipoprotein or high-density lipoprotein cholesterol, or age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of NEAT1-/- splenocytes identified disturbed expression and regulation of chemokines/receptors, innate immunity genes, tumour necrosis factor (TNF) and caspases, and increased production of reactive oxygen species (ROS) under baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell differentiation. NEAT1-/- bone marrow-derived macrophages (BMDMs) displayed altered transcriptomes with disturbed chemokine/chemokine receptor expression, increased baseline phagocytosis (P < 0.0001), and attenuated proliferation (P = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (P < 0.0001) ROS production and disturbed phagocytic activity (P = 0.0318). Monocyte-macrophage differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice displayed aortic wall CD68+ cell infiltration, and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals. CONCLUSION: The study indicates distinctive alterations of lncRNA expression in post-MI patient PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part of a molecular circuit also involving several chemokines and interleukins persistently deregulated post-MI. Individual profiling of this circuit may contribute to identify high-risk patients likely to benefit from immunomodulatory therapies. It also appears reasonable to look for new therapeutic targets within this circuit.

Correlation between increased orbital volume and enophthalmos and diplopia in patients with fractures of the orbital floor or the medial orbital wall.

Fractures of the orbital floor and medial orbital wall (blowout fractures) are common midface injuries. Diagnostic methods and treatment options have improved over recent years, due to threedimensional image processing and the use of patient-specific implants. Nonetheless, the indications for orbital reconstructive surgery are still controversial. Previous authors have reported a linear correlation between post-traumatic increases in orbital volume and enophthalmos and diplopia. Post-traumatic increases in orbital volume are often considered to be predictive of long-term symptoms; therefore, it is commonly recommended that orbital volume increases be treated as an indication for early reconstructive surgery. However, the results of this study did not show any statistically significant long-term linear correlation between increased orbital volume and enophthalmos or diplopia, and the performance of orbital volume as a predictor of ocular symptoms was poor. Hence, we do not consider increased post-traumatic orbital volume to be particularly useful for predicting late enophthalmos or diplopia. However, a statistical correlation between fractures of the anterior and medial thirds of the orbital floor and double vision was found. As such, fractures of the middle and anterior third should be regarded as problematic, and surgical reconstruction should be considered in these cases.

Intraoperative 3-dimensional cone beam computed tomographic imaging during reconstruction of the zygoma and orbit.

OBJECTIVE: Fractures of the zygoma and orbit are common facial skeleton injuries. Inadequate reduction and internal fixation may result in functional and aesthetic impairment. The aim of this study was to assess the use of intraoperative 3-dimensional (3-D) cone beam computed tomography (CBCT) for determining the intraoperative revision rate and the need for additional reconstruction of the orbit. STUDY DESIGN: We conducted a retrospective analysis of 48 consecutive patients (15 females, 33 males) suffering from simple or complex zygomatic fractures, seen between June 2015 and October 2016. Intraoperative 3-D CBCT (Xoran Technologies, Ann Arbor, MI) was performed, and the intraoperative image was overlaid on the preoperative image by using iPlan software (Brainlab, Feldkirchen, Germany) for quality control. Categorical variables were cross-tabulated and compared using Fisher's exact test. P values and 95% confidence intervals were assessed. RESULTS: In 6 of 48 patients, intraoperative revision was deemed necessary on the basis of the superimposition on the preoperative images. Five of these 6 patients had comminuted fractures (P = .001). In 7 patients, the indication for orbital reconstruction was revised after intraoperative 3-D CBCT. CONCLUSIONS: Intraoperative 3-D CBCT allows for immediate revision and prevents unnecessary orbital reconstruction.

Comparison of preseptal and retroseptal transconjunctival approaches in patients with isolated fractures of the orbital floor.

Transconjunctival approach has become a standard procedure to access fractures of orbit and the infraorbital rim. The transconjunctival incision can be performed pre- or retroseptally. Both approaches have been described combined with modifications such as transcaruncular or detachment of the lateral canthus for wider exposure of the orbital walls and rim. Particularly concerning aesthetics, the transconjunctival approach shows advantages compared to the transcutaneous incisions, such as the transciliary and infraorbital access. Moreover, transconjunctival approach is preferred in the literature regarding lid retraction. In this study the preseptal approach is compared with the retroseptal approach concerning en- or ectropion, foreign body sensation and formation of symblepharon. In our collective complication rates were lower in the retroseptal transconjunctival group, although this was not statistically significant. Whether the preseptal or the retroseptal transconjunctival approach is selected, is rather based on the surgeon's preferences. Nevertheless, the retroseptal approach must be considered as advantageous alternative to the preseptal approach because of simpler surgical technique and the safer distance to the vulnerable lid apparatus.

Use of a monopolar microneedle device in a transconjunctival, retroseptal approach.

Transconjunctival approach is a standard procedure to address fractures of orbit and the infraorbital rim. Modifications such as transcaruncular or lateral canthal widening allow for extended orbital wall exposure. Especially concerning aesthetics, the transconjunctival approach shows benefits compared to the transcutaneous incisions, such as the transciliary and infraorbital access. Moreover, transconjunctival approach is favored in the literature concerning lid retraction. Monopolar devices have become popular in surgery in the past decades because of good depth control and simultaneous hemostasis with consequently improved overview. Also numerous surgeons use monopolar device in orbital surgery, their safety have never been proved. In this study monopolar microneedle device is compared with conventional access by scalpel concerning lid retraction, foreign body sensation and formation of symblepharon. In our collective complication rates were comparable between the scalpel and the microneedle group. The monopolar microneedle device shows favorable results compared with the scalpel and is easy to handle. Weather the conventional access by scalpel or the access by monopolar device is selected, is rather driven by the surgeon's preferences than by statistical relevance. Nevertheless, monopolar microneedle device shows better depth control and simplifies readaptation of the conjunctival wound's margin.

Closed versus open treatment of mandibular condylar process fractures: A meta-analysis of retrospective and prospective studies.

INTRODUCTION: The treatment of fractures of the mandibular process remains controversial, although there is a trend towards open reduction and internal fixation. This study compared open and closed treatments and assessed the results with a meta-analysis. MATERIALS AND METHODS: A literature search of PubMed found eight studies that met the search criteria and were included in the meta-analysis. RESULTS: The studies increasingly suggest better results for open treatment, in terms of mouth opening, protrusion, laterotrusion, pain, and malocclusion. In the meta-analysis, the outcome was significantly better for laterotrusion and protrusion in patients treated by open reduction and internal fixation. CONCLUSION: Due to the different study protocols and lack of information on classification, follow-up time, and inclusion criteria, comparison of the studies remains difficult and further prospective, randomized studies should examine these issues.

Decelerated vascularization in tissue-engineered constructs in association with diabetes mellitus in vivo.

AIMS: Rapid blood vessel ingrowth in transplanted tissue engineering constructs is the key factor for successful incorporation, but many potential patients who may use engineered tissues suffer from widespread diseases that limit the capacity of neovascularization (e.g. diabetes). Thus, in vivo vascularization analyses of tissue-engineered constructs in angiogenically affected organisms are required. METHODS: We therefore investigated the in vivo incorporation of collagen-coated and cell-seeded poly-L-lactide-co-glycolide scaffolds in diabetic B6.BKS(D)-Lepr(db)/J mice using repetitive intravital fluorescence microscopy over a time period of two weeks. For this purpose, scaffolds were seeded with osteoblast-like or bone marrow mesenchymal stem cells and implanted into the dorsal skinfold chambers of diabetic and non-diabetic (C57BL/6) mice. RESULTS: Apart from slightly increased inflammatory parameters, diabetic mice showed significantly reduced capillary densities compared with non-diabetic animals from day 6 onward. In line with previous studies, more densely meshed microvascular networks were demonstrated in cell-seeded than in collagen-coated scaffolds from day 6 onward within the single groups (diabetic and control). CONCLUSIONS: A large number of patients who suffer from systemic diseases that affect angiogenesis would profit from tissue engineering. Therefore, the challenge for the clinical introduction of tissue-engineered constructs will be to overcome the decreased angiogenesis in diabetic organisms.

Unknown primary of the head and neck: A long-term follow-up.

BACKGROUND: A diagnosis of squamous cell carcinoma of an unknown primary (CUP) is a major burden for patients. Because the location of the primary tumor is unclear, patients remain fearful of recurrence, which aggravates the uncertain prognosis of the disease. This study evaluates factors associated with long-term recurrence-free and overall survival of patients with CUP of the head and neck. Additionally, patient survival rates are compared with those of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 293 consecutive patients operated on between January 1999 and December 2009 with at least a 5-year follow-up (survival permitting), were evaluated retrospectively. RESULTS: Twenty-six patients with a CUP of the head and neck were identified. Patients with CUP had a low overall survival rate, comparable with that of patients with pN + HNSCC, and recurrent disease occurred with a similar likelihood as in patients with pN + HNSCC. The median recurrence-free survival in the CUP group was 28.5 months compared with 48 months in the whole of the HNSCC group. The median overall survival of the CUP group was 56 months versus 65 months for the HNSCC group. Extracapsular spread was the only independent prognostic factor for overall survival for CUP patients. CONCLUSION: Patients diagnosed with CUP syndrome have a poorer prognosis for overall survival compared with other HNSCC patients. Postoperative radiotherapy diminished disease recurrence and improved overall survival. Omission of postoperative radiotherapy resulted in a very high recurrence rate (75%) for CUP patients. Based on these results we suggest postoperative radiotherapy including the oral mucosa for all patients, regardless of histopathological results, possible favorable nodal disease, or favorable lymph node ratios.

Patient specific implants (PSI) in reconstruction of orbital floor and wall fractures.

Fractures of the orbital wall and floor can be challenging due to the demanding three-dimensional anatomy and limited intraoperative overview. Misfitting implants and inaccurate surgical technique may lead to visual disturbance and unaesthetic results. A new approach using individually manufactured titanium implants (KLS Martin, Group, Germany) for daily routine is presented in the current paper. Preoperative CT-scan data were processed in iPlan 3.0.5 (Brainlab, Feldkirchen, Germany) to generate a 3D-reconstruction of the affected orbit using the mirrored non-affected orbit as template and the extent of the patient specific implant (PSI) was outlined and three landmarks were positioned on the planned implant in order to allow easy control of the implant's position by intraoperative navigation. Superimposition allows the comparison of the postoperative result with the preoperative planning. Neither reoperation was indicated due to malposition of the implant and the ocular bulb nor visual impairments could be assessed. PSI allows precise reconstruction of orbital fractures by using a complete digital workflow and should be considered superior to manually bent titanium mesh implants.

Modified technique for rehabilitation of facial paralysis using autogenous fascia lata grafts.

PURPOSE: In this retrospective study we used a modified surgical technique for midface reanimation in patients with facial nerve paralysis. Facial atonicity can cause functional impairment regarding speech articulation, oral competence, breathing, and eyelid closure. Furthermore, esthetic and psychological aspects play an important role in patients' emotional interaction and social integration. The chosen rehabilitative technique should offer support against prolapse of facial structures and remedy of functional disabilities and, thereby, prevention of social stigmatization due to disease-related changes in appearance. MATERIALS AND METHODS: Between 2005 and 2013, fascia lata grafts were used as static support in 15 cases of unilateral facial paralysis. Two fascia lata grafts were subcutaneously inserted in the upper and lower lips crossing the midline and sutured at 4 points, including the unaffected part of the orbicularis oris muscle and modiolus. The slings were suspended against the zygomatic arch with an osteosynthesis plate. RESULTS: The patients perceived surgery results as considerably improving their appearance, speech, and alimentation. In 93.3% of cases, no postoperative complications occurred. The follow-up results (8 months to 8 years) remained stable. CONCLUSIONS: This retrospective study showed the advantages of static facial reanimation in appropriate cases. The bony fixated support of the fascial slings allows an immediate improvement of facial symmetry. Additional attachment points including the unaffected part of the orbicularis oris muscle and the use of 2 independent fascia lata slings allow a more accurate adjustment of suspension forces and an incomplete dynamic reanimation of the mouth corner. With respect to its simplicity and minimal invasiveness, this surgical procedure is associated with low morbidity and rapid improvement of the patient's esthetic appearance.

Diagnosis and treatment of optic nerve trauma.

Decreasing visual acuity secondary to orbital trauma or orbital and anterior skull base surgery may be caused by either sudden space-occupying intraorbital lesions, including retrobulbar hemorrhage (RBH), or direct damage to the prechiasmatic pathway. Contrary to traumatic optic neuropathy, RBH must be diagnosed and treated immediately to prevent permanent damage to the visual system. Therefore, monitoring and handling of visual pathway damage are mandatory. Flash visual evoked potentials and electroretinograms can provide evidence of the status of conductivity of the visual pathway when clinical assessment is not feasible. Both are thus essential diagnostic procedures not only for primary diagnosis but also for intraoperative evaluation. In case of RBH surgical decompression is compulsory. However, traumatic optic neuropathy does not respond to either corticosteroids or optic canal surgery. Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity.