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There is limited experience with facial re-transplantation (fRT). We report on the management of facial re-transplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation. We summarize the events between the two transplantations, focusing on the final rejection episode. We describe the surgical technique of facial re-transplantation, the immunological and psychosocial management, and the six-month post-operative outcomes. Removal of the old allograft and inset of the new transplant were done in one operation. The donor and recipient were a good immunological match. The procedure was technically complex, requiring more proximal arterial anastomoses and an interposition vein graft. During the first and second transplantation the facial nerve was coapted at the level of the branches. There was no hyperacute rejection in the immediate postoperative phase. Outcomes six months postoperatively are promising. We provide proof-of-concept that facial re-transplantation is a viable option for patients who suffer irreversible facial vascularized composite allograft loss.

Background Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared to conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. Methods We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥ 3 years follow-up, were included. Results The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic and/or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. Conclusions Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression related complications, and heterogeneity in outcome reporting present ongoing challenges in this field.

SUMMARY Skin is one of the target tissues of rejection in face transplants and, because of its easy accessibility, has become the gold standard in the diagnosis of rejection. The allograft contains deeper tissues where rejection can occur, but samples cannot be obtained because of difficult access. Deep tissue changes were monitored on computed tomographic scans of the midface in six face transplant recipients with the help of image segmentation. The maxillary sinus was identified as a dynamic anatomical compartment. Observed changes in volume of the aeration relative to the opacification (aeration coefficient) of the maxillary sinus were quantified with the help of image segmentation. Changes in the aeration coefficient as a surrogate of mucosal swelling were quantified and related to time, treatment, and skin rejection grade. Lower aeration coefficients were found only in patients with transplanted maxillary sinus mucosa. Pathologic changes were not observed in face transplant recipients with a native maxillary sinus. The data show that the aeration coefficient was significantly lower at the time of biopsy-proven allograft rejection. Neither mechanical, nor infectious, nor medication side effects sufficiently explain the findings presented herein. The authors' findings are important to consider for clinical management of face transplant patients who receive parts of the sinonasal tract. The authors identify a potential radiologic biomarker of deep tissue allograft rejection. In the future, the proposed methodology might prove useful in monitoring deeper dynamic tissue changes in vascularized composite allografts and might help in designing patient-specific, individualized treatment strategies.

There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation.This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed.We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R-). CMV viremia was noted in 6 patients (all 4 D+/R- patients and 2 D-/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 D+/R- patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R- patients suffered allograft loss due to rejection (longest follow-up: 121 mo).D+/R- patients were at increased risk of CMV-related complications. Although a higher number of rejections was noted in this group, none of the D+/R- patients lost their allograft or died because of CMV or rejection. Thus, CMV D+/R- face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment.

The pterygopalatine fossa (PPF) is a complex and paired anatomical structure located at the skull base. A clinically and surgically relevant structure located in the pterygopalatine fossa is the sphenopalatine ganglion. Electrical stimulation of the sphenopalatine ganglion is one possible method of treating cluster headache. The pterygomaxillary fissure (PMF) defines the pterygopalatine fossa laterally and determines the surgical approach. As part of preoperative surgical planning, each patient undergoes a preoperative head computed tomography or a cone beam computed tomography. In our study cone beam computed tomography images of 90 male and 110 female PMF were analyzed. Generally, males have a wider fissure than females. Moreover, a significant inter-subject difference could be shown between males and females. The analysis of the right and left PMF according to gender and age does not show any significant intra-subject differences. Following an established protocol for high-resolution CT images the measurements were classified into four fissure types and also analyzed according to gender and age. Fissure type I is significantly more often present in males, whereas the smaller fissure types (II, III, and IV) are significantly more often found in females. Older patients presented statistically significant more often with type I, whereas the younger patients showed more often the narrower types II and IV. Due to the fact that narrow fissures smaller than 2 mm could limit the insertion of neurostimulator implants in the PPF, special attention should be paid to females and younger patients during preoperative planning.

Purpose The aim of this prospective work was to examine oral leukoplakia for their podoplanin expression to determine whether podoplanin expression is associated with the degree of dysplasia. Materials and methods We took biopsy samples from 50 patients with oral leukoplakia in 2013. The preparations studied by immunohistochemistry were analyzed in correlation with the degree of dysplasia and other clinicopathological variables. Results The Chi-square test showed a significant correlation between podoplanin expression and the degree of dysplasia according to the squamous intraepithelial neoplasia (SIN) classification (p = 0.033). Also, a significant association between age grouping and podoplanin expression was found. We were able to show that the distribution is the same for both age groups in relation to the score of podoplanin expression (p = 0.003). Conclusion In a comparable retrospective work of our working group, it could be shown that podoplanin is a reliable predictive marker for the assessment of the risk of malignant transformation. The present work was able to substantiate the assumption that podoplanin not only plays an important role in the context of malignant degeneration but also exerts a major influence in advance.

Tumor invasion into blood and/or lymphatic vessels, perineural invasion, and histopathological grading are evaluated to assess the biological aggressiveness of oral squamous cell carcinoma (OSCC). We aim to assess the prognostic impact of a novel scoring system, based upon the aforementioned histological parameters. Retrospective chart review of 334 patients with treatment-naive squamous cell carcinoma of the oral cavity. Statistical analysis was performed using univariate and multivariate analysis. Histological grade G1 or G2 were assigned 0 points and G3 or G4 1 point. Invasion of the lymphatic vessels, blood vessels, or perineural space was given 1 point. Zero points were given, when invasion was not detectable. The final score was conducted through addition of each parameter. Therefore, our scoring system ranged between 0 and 4 points. T-classification (p

Introduction The subject of the present study was a systematic comparative analysis of the rheumatoid arthritis (RA)-induced pathomechanisms in the temporomandibular joint with those of the limb joints using the serum-induced arthritis K/BxN model. Methods In 18 BALB/c mice the induction of RA was performed according to the Kouskoff method. Another healthy cohort served as controls (n = 12). Joint swelling of the paws was measured using a micrometer. Functional data were obtained analyzing locomotion. Three-dimensional examination of the temporomandibular joint was performed with micro-computed tomography imaging, followed by histological evaluation of the extremity joints and the temporomandibular joint. Additionally, immunohistochemical investigations were carried out to evaluate inflammatory and immunological changes. Results Measurement of joint swelling showed a significant increase in the diameter of the paws, as well as a decrease in locomotor activity compared to control animals and the time before arthritis induction. Histological and immunohistochemical investigations showed clear signs of inflammation in the extremity joints. In contrast, no histological or immunohistochemical indications of an inflammatory process were detectable in the temporomandibular joint. In addition, the three-dimensional analysis by micro-computed tomography of the temporomandibular joints did not show any obvious morphological changes. Conclusion For the first time, using the K/BxN model we could demonstrate that, due to its anatomical and mechanical conditions, the temporomandibular joint seems to be less susceptible to the initiation of RA compared to limb joints. Therefore, additional investigations are needed on other arthritis models as well, in order to further improve our understanding of the pathogenesis and defense mechanisms of the disease.

Background Identifying a donor for facial vascularized composite allotransplant recipients can be a lengthy, emotionally challenging process. Little is known about the relative distribution of key donor characteristics among potential donors. Data on actual wait times of patients are limited, making it difficult to estimate wait times for future recipients. Methods The authors retrospectively reviewed charts of nine facial vascularized composite allotransplant patients and provide data on transplant wait times and patient characteristics. In addition, they analyzed the United Network for Organ Sharing database of dead organ donors. After excluding donors with high-risk characteristics (e.g., active cancer or risk factors for blood-borne disease transmission), the authors calculated the distribution of relevant donor-recipient matching criteria (i.e., ethnicity, body mass index, age, ABO blood group, cytomegalovirus, Epstein-Barr virus, hepatitis C virus) among 65,201 potential donors. Results The median wait time for a transplant was 4 months (range, 1 day to 17 months). The large majority of United Network for Organ Sharing-recorded deaths from disease were white (63 percent) and male (58 percent). Female donors of black, Hispanic, or Asian descent are underrepresented, with 7, 5, and 1 percent of all recorded deaths from disease, respectively. Potential donors show cytomegalovirus and Epstein-Barr virus seropositivity of 65 and 95 percent, respectively. The number of annual hepatitis C-positive donors increased over time. Conclusions Actual facial vascularized composite allotransplant wait times vary considerably. Although most patients experience acceptable wait times, some with underrepresented characteristics exceed acceptable levels. Cytomegalovirus-seropositive donors present a large portion of the donor pool, and exclusion for seronegative patients may increase wait time. Hepatitis C-seropositive donors may constitute a donor pool for underrepresented patient groups in the future.

OBJECTIVES Mandible fractures can be treated with different plate systems, that is, miniplates or three-dimensional (3D) plates. This systematic review describes the effectiveness and clinical outcomes of 3D plates used in fractures of the mandible and aims to critically evaluate its risks and benefits. MATERIALS AND METHODS A comprehensive electronic search was conducted without date but with restriction to articles written in English. Studies in humans, including randomized or quasi-randomized controlled trials and retrospective studies, were included. The outcome parameters measured were number of patients, fracture classification, results, follow-up period, postoperative complications, and mean age of patients. Major complications were defined as those needing additional surgical intervention, for example, malocclusion, infection or plate fracture. Accordingly, complications not needing additional surgical intervention were defined as minor (ie, dehiscence, trismus). RESULTS Guided by the PRISMA statement and the Cochrane Handbook for Systematic Reviews of Interventions, the authors identified 44 publications with a total of 1790 patients. Among the articles selected for the final review, there were 32 reported prospective studies, 12 reported retrospective studies. Regarding the evaluation of quality, 8 studies showed a low value of the risk of bias, 17 a moderate risk, and 19 a high risk. There were statistically significant advantages for 3D plates in mandibular fractures in terms of postoperative complications, for example, wound dehiscences or plate fracture. CONCLUSIONS The 3D plate is an effective treatment modality for mandibular fractures, with low incidence of major complications, decreased length of operation time, and increased stability of osteosynthesis.

Objective Bone substitute (BS) size might influence the clinical outcomes of guided bone regeneration (GBR) procedures. The aim of the present study was to investigate the influence of BS size on macrophage (Mφ) and osteoblast behaviors in vitro. Materials and methods Two different granule sizes (S and M/L) were assessed for four different commercial BSs: deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate type 1 (BCP1), BCP type 2 (BCP2), and carbonate apatite (CO3Ap). The BSs were compared for their impacts on the cell viability and differentiation potential of THP-1-derived Mφs and human osteoblast-like Saos-2 cells. Results The smaller granules showed higher material volumes and surface areas than the larger granules. Significantly higher viability of Mφs and Saos-2 cells was observed with the DBBM_L-size granules than with the DBBM_S-size granules. Gene expression experiments in Mφs revealed few differences between the two sizes of each BS, although higher CD206 mRNA levels were observed in the BCP1_L group and the CO3Ap_M group than in the respective S-size groups on day 1. Only DBBM showed significantly higher mRNA levels of osteogenic markers, including Runx2 and osteocalcin, in Saos-2 cells in the S-size group than in the L-size group. Conclusions The S-size and L-size DBBM granules exhibited clear differences in cell outcomes: cells cultured on the S-size granules exhibited lower cell viability, higher osteopromotive ability, and no noticeable Mφ polarization changes. Clinical relevance A smaller granule size might be advantageous due to greater bone regeneration potential in the use of DBBM granules to treat defects.

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BACKGROUND Cutaneous changes of facial vascularized composite allotransplants (fVCAs) are extensively described in the literature. Parts of the nose, nasal, and oral cavities are included in most fVCAs. Distinctively, the nose and mouth are lined by mucosa. Little is known about the histopathology and complications of the mucosa involved in fVCA patients. METHODS The study constitutes a retrospective cohort study of nine fVCA patients. Medical records were reviewed for information about changes of oral and nasal mucous membranes. Types of mucosal lesions were recorded and analyzed. Uni- and multivariate generalized estimating equation (GEE) models were used to assess the odds of developing mucosal inflammation in the presence of clinico-pathologic variables. RESULTS A total of 186 clinical encounters with examination of oral and nasal mucous membranes were included. Membranes were devoid of clinical pathology in 101 instances (53% of all clinical assessments). Ulcerations/erosions (27%), edema (18%), and erythema (14%) were the most common lesions. Oral lesions affected the lips (58%), buccal mucosa (38%), and palate (5%). Sinonasal processes predominantly affected nasal vestibules and septae. In univariate analysis, sirolimus, skin rejection, and skin Banff grade were associated with the presence of an acute inflammatory mucosal lesion (p

Background : Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowed VCA in humans. However, repeated rejection episodes are common and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulative approaches to improve allograft acceptance and to minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field. Methods : We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed database. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging survival of a skin containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results : The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind-limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulative strategies used in VCA-preclinical research over a timeframe of 44 years. Conclusion : We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind-limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.

The aim of this study was to provide volumetric data of the pterygopalatine fossa by semiautomatic segmentation based upon cone beam computed tomography.Cone beam computed tomography (CBCT) images of 100 patients were analyzed. By using the open source software "ITK-Snap," the volumetric measurements of 200 pterygopalatine fossae were performed. For statistical investigations paired t test, and independent Student t test were performed. Also, the Pearsons chi-square test was applied. P values P 0.05 were considered significant.The mean volume was 578.376 mm for the right and 560.979 mm for the left side. The results indicated statistically significant differences according to the right and the left pterygopalatine fossa, regardless of gender (P 0.05). The analysis of differences between males and females did not show any significant results (P 0.05), although males present a slightly larger volume than females. According to the median age (59 years), younger patients presented smaller volumes, whereas older patients presented larger volumes. Nevertheless, no statistically significant differences according to age (χ = 3.520; P 0.05) could be found.Clinical intervention with the application of local anesthetics into the complex and vulnerable anatomy of the pterygopalatine fossa makes a thorough knowledge about the volumetric capacity indispensable. Therefore, the semiautomatic segmentation of CBCT images provides a useful, available and validated tool. Our results show that a final injected anesthetic volume larger than 1 ml exceeds the pterygopalatine fossa capacity considerably and could cause complications. To prevent this, volumetric analysis of this region can provide further information and enables an individualized patients' treatment.

BACKGROUND Machine perfusion (MP) has evolved as a promising approach for the ex situ preservation in organ transplantation. However, the literature on the use of MP in human vascularized composite allografts is scarce. The aim of this study was to evaluate the effects of hypothermic MP with an acellular perfusate in human upper extremities and compare with the current gold standard of static cold storage (SCS). METHODS Six upper extremities were assigned to either MP (n = 3) or SCS (n = 3) conditions for 24 h. MP-extremities were perfused with oxygenated Steen solution at a constant pressure of 30 mm Hg and 10°C. RESULTS Median total ischemia time was 213 min (range, 127-222 min). Myoglobin, creatine-kinase (CK) showed increased levels at the start of MP (medians: myoglobin: 4377 ng/mL, CK: 1442 U/L), peaking 6 h after perfusate exchange (medians: myoglobin: 9206 ng/mL, CK: 3995 U/L) at timepoint 24. Lactate levels decreased from a median of 6.9-2.8 mmol/L over time. Expression of hypoxia-inducible factor 1-alpha peaked in the SCS-group after 8 h, followed by a decrease. Increased hypoxia-inducible factor 1-alpha expression in the MP group was delayed until 20 h. Perfusion pressure, temperature, and circuit flow were maintained at median of 30.88 mm Hg, 9.77°C, and 31.13 mL/min, respectively. Weight increased 1.4% in the SCS group and 4.3% in the MP group over 24 h. CONCLUSIONS Hypothermic ex situ perfusion with an oxygenated acellular Steen solution may extend the allowable extracorporeal preservation time by a factor of 4-6 compared to SCS and holds promise to be beneficial for vascularized composite allograft recipients and victims of traumatic major limb amputation.

Facial vascularized composite allotransplantation (fVCA) presents an established approach to restore form and function of patients with catastrophic facial defects. Skin is one of the target tissues of the rejection process, and due to its easy accessibility has become the gold standard in the diagnosis of rejection. Mucosal rejection frequently occurs; however, the added value of mucosal rejection assessment for patient management is unknown.We conducted a systematic review of manuscripts listed in the MEDLINE/PubMed and GoogleScholar databases to identify articles that provide data on mucosal rejection following fVCA. For inclusion, papers had to be available as full-text and written in English. Non-VCA studies and animal studies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.We included 17 articles that described changes in allotransplanted mucosa of fVCAs. These articles yielded data on 168 BANFF graded biopsies of corresponding skin and mucosa biopsies. Rejection grades were consistently higher in mucosal biopsies. Concordance between allograft skin and mucosa biopsy grades increased with an increasing skin-BANFF grade. Mucosa rejection grades were on average lower in the early stages of the posttransplant period (postoperative mo 12, time of motor, and sensory recovery) when compared to the later stages (postoperative mo 12).The mucosa of facial allotransplants is one of the primary targets of rejection. The data indicates that higher-grade skin rejection does not occur in absence of mucosal rejection. Further investigations are needed to elucidate the exact role of mucosal biopsies for fVCA patient management.

The authors present a novel biological nonliving epineurial nerve coaptation training model, which allows cost-efficient practicing on organic mammal nerves and offers an objective performance control on the basis of successful suturing and respecting the 3R model.Anatomic dissection of 40 rat cadavers was performed. Four residents without prior microneurosurgical experience were included. Each trainee performed 20 epineurial nerve coaptations. The number of successful sutures served as qualitative variable and operation time as a quantitative variable for efficiency control.The rate for successful sutures was 51.9% in the first half of trials and improved to 94.4% in the second half. Whereas, the trainees needed a mean time of 34 minutes for the first 10 coaptations, the last 10 coaptations were performed within 24.5 minutes.The authors' presented model is an easily accessible, low-cost microneurosurgical simulation model, allowing a realistic and instructive performance of epineurial nerve coaptation. Because cadaveric nerves are used, an approval of the local ethics committee is not needed. Furthermore, anatomic knowledge about the topography related to the harvest of the sciatic nerve of rats is provided in this study.

The present investigation constitutes a retrospective evaluation of the outcome in children who received surgical correction of a scaphocephalic phenotype by median total vertex craniectomy. Between September 2009 and September 2015, a total of 35 infants with non-syndromic scaphocephaly were treated according to the same standardized operative technique of total vertex craniectomy by a single surgeon approach. At the time of surgery, the patients were between 3 and 12 months of age, with a median of 5 months. The mean duration of the procedure was 94 min. The duration of postoperative follow-up was a mean of 24 months (range 6-49 months). A total of 34 (97%) patients were successfully treated by total vertex craniectomy and were thus classified as category I according to the Whitaker score. Only one individual was assigned to category IV, necessitating secondary major craniofacial corrective surgery. Aesthetic outcomes were excellent in 34 cases and poor in one case. No major complication occurred. The reoperation rate was 3%. The surgical method we present herein is a wide median craniectomy which can be applied in young individuals with non-syndromic single-suture scaphocephaly.

BACKGROUND For successful reshaping of the cranial vault in terms of corrective fronto-orbital advancement (FOA) efficient and reliable internal fixation systems for stabilization of bone fragments are indispensable. The rate of complications and feasibility of corrective FOA with the usage of titanium-based rigid fixation systems is rarely analyzed and discussed. METHODS The authors retrospectively reviewed the medical records of 42 patients who received corrective FOA with the implementation of titanium internal rigid fixation and consecutive secondary surgery for removal. The reliability of the fixation system was judged by the outcome of the FOA as evaluated by the Whitaker score, esthetic outcome as well as by the complication rate of the secondary intervention, necessary for removal of the fixation system. RESULTS All patients were categorized as Whitaker I (no further treatment desirable). Esthetic outcome was excellent in all patients as judged by surgeon and parents. Mean age at the time of FOA was 9.3 months. Time to removal, duration of the second hospital stay for removal of the fixation system, and duration of surgical drains were on average 5 months, 2 days, and 1.7 days, respectively. Mean duration of the secondary surgery was 63 min. No complications occurred. CONCLUSION Our investigation supports the usage of titanium internal rigid fixation systems in pediatric craniofacial surgery, thereby providing a reliable alternative to avoid the well-documented problems of bio-absorbable plate fixation systems.

In consideration of the 3-R-rule (Refine-Replace-Reduce) as a guideline for promoting ethical use of animals for surgical training, we present a novel training model for microvessel anastomosis. In a rat cadaveric study, we evaluated the surgical anatomy of the common carotid artery (CCA), external jugular vein (EJV) and femoral vessels (FV) which were then used as templates for the present investigation. Anatomical dissection of 30 rat cadavers was performed. Two residents without prior microsurgical experience were included in the study and performed 5 CCA, 5 femoral artery, 5 EJV and 5 femoral vein anastomoses. Patency and leakage served as qualitative variables and operation time as a quantitative variable for efficiency control. The average time improved for arterial and venous anastomoses (45 min–22 and 60 to 32 min, respectively) for both surgeons. While both surgeons experienced patency failure or leakage within the first half of performed arterial and venous anastomoses, they could improve to a 100% patency rate without the occurrence of leakage for the last half of trials. The rat head & neck anatomy presents various characteristics related to the harvest of the vessels of interest. We provide anatomical knowledge about the topography related to the harvest of the CCA, EJV, and FV. Our model is an easily accessible, low-cost microsurgical simulation model, allowing a realistic and instructive performance of anastomoses. Since cadaveric vessels are used, an approval of the local ethics committee is not needed.

Recent studies highlighted the prognostic superiority of lymph node volume towards the conventional N Classification. However, data on the importance of neck lymph node volume, obtained by semiautomatic segmentation of CT images, do not exist for locoregional recurrence in patients with oral squamous cell carcinoma (OSCC).Retrospective chart review of 100 patients, who were diagnosed and treated between 2006-2014. Inclusion criteria were patients with treatment-naive oral squamous cell carcinoma and primarily curative intended surgery with negative resection margins, for whom a preoperative computed tomography (CT) of the head and neck region was performed. Furthermore, comprehensive neck dissection (level I-V) due to ipsilateral lymph node metastasis was chosen as inclusion criterion. Exclusion criteria were neoadjuvant chemoradiotherapy, T4b classification, perioperative death, unresectable disease, synchronous malignancy, follow-up3 months and inadequate information to correctly determine clinicopathological characteristics.Pathological N Classification (p = 0.001), central necrosis (p = 0.008) and lymph node volume (p 0.001) significantly affected locoregional recurrence (p 0.001). Multivariate analysis indicated N Classification (p = 0.06) and volume (p 0.001) as indepedent risk factors for locoregional recurrence.Volumetric measurement serves as a better risk stratification tool than the conventional N Classification for OSCC. A lymph node volume of more than 6.86 cm

The authors' aim was to provide volumetric data of mandibular condyles based upon cone beam computed tomography with the means of semiautomatic segmentation.Retrospective chart review of 350 patients (700 mandibular condyles) with cone beam computerized tomography between February 2007 and December 2016. Univariate analysis was performed to analyze associations between variables. P values

A precise knowledge of the condylar changes with advancing age may improve understanding of pathophysiological alterations of the mandibular condyles. However, the majority of studies focusses on morphological changes, although volumetric analysis based upon cone beam computerized tomography may provide important additional data to characterize mandibular condyles. Therefore, we aimed to provide and compare volumetric data of mandibular condyles of a young and old patient group. This is a retrospective chart review of 195 patients with cone beam computerized tomography between 2007 and 2016. Student t test, analysis of variance, and Pearson correlation test were performed to analyze associations between categorical and continuous variables. P values

Background Sinonasal sarcomas are rare and heterogeneous in nature. Continuously collecting data influencing the prognosis is fundamental for optimizing therapeutic assessment of this highly destructive neoplasm. Methods We conducted a single-institution retrospective cohort study considering 27 patients with sinonasal sarcoma. Results The overall survival (OS) rates for 1 year and 5 years were calculated as 74% and 36%, respectively. Extent of the primary tumor (P = .010), nodal spread (P = .009), and age (P = .004) significantly reduced the OS. Disease-free survival (DFS) was significantly reduced by age (P = .003), extent of the primary (P = .006), nodal (P = .004), and hematogenous (P = .048) spread. Multimodal therapy including surgery improved the OS and DFS rates (P Conclusion Prognosis is poor due to late disease recognition. However, multimodal therapeutic regimens, including surgery, may improve the outcome.

The keratocystic odontogenic tumor (KCOT) is capable of causing vast osseous destruction. Histopathological examination is pivotal for diagnosis. The diagnostic process can sometimes be hindered by tissue inflammation of KCOTs with loss of defining criteria, resulting in misdiagnosis as an odontogenic jaw cyst. We discuss the possible merits of volumetric analysis when facing this particular diagnostic dilemma and for pathophysiological characterization of KCOTs. We included 114 patients, of whom 27 were histopathologically diagnosed with a KCOT and 87 with dentigerous (n = 41) and periapical cyst (n = 46). Semiautomatic segmentation and radiological analysis of preoperative cone beam computed tomography (CBCT) image data was carried out using ITK-SNAP. The mean volumetric extent of KCOTs is significantly higher compared to non-neoplastic odontogenic jaw cysts (p = 0.001). The mean volume and standard deviation for KCOTs and non-neoplastic odontogenic jaw cysts was 10381 mm 3 ± 6410 and 5813 mm 3 ± 4425, respectively. Volumetric analysis reveals that KCOTs significantly exceed the mean size of non-neoplastic odontogenic jaw cysts, adding an argument in favor of the neoplastic nature of KCOTs. In the case of difficult histopathological examination, lesions with a size exceeding a value of about 3000 mm 3 could be considered for close clinico-radiologic follow-up.

Nodal yield has been demonstrated as a very promising marker for the prognostic outcome of patients with oral squamous cell carcinoma. However, studies on the importance of clinicopathological factors affecting the number of resected lymph nodes are rare, especially for patients without pathologically proven cervical lymph nodes.Retrospective chart review of 264 patients with treatment naive oral squamous cell carcinoma and histopathologically proven negative cervical lymph node status, who received selective neck dissection of levels I-III/IV. Exclusion criteria were neoadjuvant chemoradiotherapy, comprehensive or bilateral neck dissection, T4b classification, perioperative death, unresectable disease, synchronous malignancy, follow-up3 months and inadequate information to correctly determine nodal yield. Statistical analysis was performed by using univariate and multivariate analysis.The mean nodal yield was 22.31 with a standard deviation of 16.01 and a mean number of 17 nodes. Gender (p = 0.018), age (p = 0.03), tumor classification (p 0.001) and perineural invasion (p = 0.012) were significantly associated with nodal yield. Multivariate analysis indicated T-classification (p = 0.049) and age (p = 0.020) as independent factors. Nodal yield was significantly associated with locoregional recurrence (p = 0.041; Cutoff value = 17).Advanced age and T-classification independently affect lymph node yields in patients with oral squamous cell carcinoma. Hence, they have to be considered for interpretation of both nodal yield and recommended minimum lymph node counts. Furthermore, resection of more than 17 lymph nodes is associated with a significantly lower risk of locoregional recurrence.

Introduction Recurrence is one of the main reasons for poor prognosis of OSCC. The mortality rate is approximately 90% and the 5-year overall survival rate decreases from 90% to 30% when recurrence is diagnosed. Identification of clinicopathological risk factors predicting recurrence may be helpful for patient individualized management and improvement of therapy. Therefore we investigated in our study the incidence of locoregional recurrences and their association with clinicopathological factors to identify possible significant risk factors. Material and methods Our retrospective study consisted of 517 patients, who were diagnosed and treated between 2003–2013 at the Department for Oral and Maxillofacial Plastic Surgery, University of Cologne. Inclusion criteria were patients with treatment naive oral squamous cell carcinoma and primarily curative intended surgery with negative resection margins. Contingency tables and χ 2 -test were performed to analyse associations between clinicopathological features and recurrence. Multivariate analysis was performed using binary logistic regression analysis. Results We found out a significant correlation in univariate analysis between locoregional recurrence and number of resected cervical lymph nodes ( p = 0.013), number of positive cervical lymph nodes ( p = 0.041), postoperative radiatio ( p = 0.018), extracapsular spread ( p = 0.028) as well as grading ( p = 0.016). In multivariate analysis only grading was shown as independent risk factor for recurrence. Conclusions Histological grading has been demonstrated as an independent risk factor for locoregional recurrence in the multivariate analysis. Furthermore, univariate analysis indicated the number of resected and positive lymph nodes, postoperative radiatio and extracapsular spread as significant risk factors. Taking these results into account, the mentioned parameters, especially histological grading, need to be considered for an individualized therapy management of patients with OSCC.

Introduction The role of the volume of radicular and dentigerous cysts on clinical symptoms is unclear and potentially may predict development of pre- and postoperative complications, especially after cystectomies with large bony defects. Therefore the aim of this study was to assess pre- and postoperative symptoms associated to the volume of jaw cysts. Material and methods Retrospective chart review of 111 patients with follicular or dentigerous cysts from 2008–2012. Anterior iliac crest grafts were used to fill defects after cystectomy. χ2-test was performed to analyze associations between two qualitative variables. Binary logistic regression analysis was used as multivariate analysis. P-values p Results Postoperative hypaesthesia correlated significantly with histology (p = 0.025) and localization (p = 0.006). Volume was associated significantly with preoperative hypaesthesia (p = 0.052), postoperative hypaesthesia (p Conclusions Volume analysis appears to be a method that allows risk stratification after surgery of jaw cysts. Therefore we recommend a precise treatment planning with the means of volume analysis to improve therapy outcome of patients with jaw cysts.

Background Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. Methods Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. Results The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6–8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient’s death 10 years after transplantation. Conclusion This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.

International audience; Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions. Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly (p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection (p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65-0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly (p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) (p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients. Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings.

OBJECTIVES The aim of the study was to investigate the association between meningioma volume and the occurrence of clinic-radiologic signs of tumor aggressiveness. For volumetric approximation, the authors evaluated the method of semiautomatic image segmentation at hand of high-resolution MRI-image sequences. METHODS ITK-SNAP was utilized for semiautomatic image segmentation of 58 gadolinium-contrast enhanced T1-weighted thin-slice MRI datasets for volumetric analysis. Furthermore, multimodal imaging datasets (including T2, FLAIR, T1) were evaluated for radiological biomarkers of aggressiveness and growth potential. Thereby generated data was checked for association with retrospectively collected data points. RESULTS Location (P = 0.001), clinical disease manifestation (P = 0.033), peritumoral edema (P = 0.038), tumor intrinsic cystic degeneration (P = 0.007), three-dimensional complexity (P = 0.022), and the presence of meningioma mass effect (P = 0.001) were statistically associated with higher tumor volumes. There was no association between higher tumor volumes and histopathological tumor grade. CONCLUSION The size of a meningioma does not seem to reliably predict tumor grade. Growth potential seems to be influenced by tumor location. Higher tumor volumes were significantly associated with the occurrence of clinical symptoms.

This study aimed to investigate the prognostic implications of comorbidity/risk factors in a cohort of patients with OSCC.The prospective study included patients with biopsy-proven primary OSCC. The impact of potential predictors on (post)operative complications, days spent in the ICU, and length of hospitalization was analyzed using both univariate and multivariate analysis.Using a microvascular free flap (p = 0.009) and tobacco abuse (p = 0.005) had statistically significant impacts on postoperative complications in univariate, but not in multivariate, analysis. The duration of anesthesia (p 0.001), type of neck dissection (p = 0.014), reconstruction type (p 0.001), and red blood cell transfusion during operation (p = 0.007) had statistically significant impacts on spending ≥ 3 days in ICU in univariate analysis, with reconstruction type (p = 0.022) and red blood cell transfusion during operation (p = 0.034) having similar impacts in multivariate analysis. The duration of anesthesia (p 0.001), pT (p = 0.009), type of neck dissection (p = 0.046), reconstruction type (p 0.001), and microvascular free flap (p 0.001) had a statistically significant impacts on length of hospitalization in univariate analysis, with reconstruction type (p 0.001) also having a significant impact in multivariate analysis.None of the investigated variables showed a significant effect on the prediction of (post)operative complications according to the Clavien-Dindo classification. The type of reconstruction proved to be a valid predictor for the time spent in ICU as well as for the overall length of hospitalization. Red blood cell transfusion during operation further predicted the time spent in ICU after operation. Both variables should be taken into account when performing a comprehensive planning of the patients' hospitalization.

Introduction Microsurgical interposition of vein grafts is an extraordinarily filigree surgical technique, which requires both sound theoretical knowledge and solid manual skills. Although there are a large number of training models, the majority of these are either relatively expensive, technically complex, or employ synthetic materials with poor resemblance to human tissue. The authors' model allows training of ex vivo vein graft interposition on gradually thawed cryopreserved vessels and it, therefore, is cost-efficient and readily available when needed. Furthermore, it respects the 3R-principle (Reduce-Refine-Replace), as it is based on rat cadaveric vessels. Methods Three trainees with basic microsurgical experience, but without prior performance of vein graft interpositioning, were chosen to perform 20 femoral vein graft (5 mm) interpositions into femoral artery defects. The patency and leakage rate served as qualitative variable and operation time as a quantitative variable for efficiency control. Results For the first half of trials, the trainees had a patency failure rate of 50% and for the second half a rate of 13.3%. The leakage rate noticeably decreased from 44.4% in the first half of trials to 10% in the second half. Although the trainees needed 60 minutes on average for their first 10 trials, they improved to 51 minutes for their last 10 anastomoses. Conclusion The authors' microsurgical model offers a simple, low-cost simulation training, specifically designed for learning of vein graft interposition into arterial defects. The model is associated with a high learning curve, based on an objective control of the anastomoses by assessment of the patency, leakage, and operation time.

Introduction Published data on procalcitonin (PCT) levels after microsurgical interventions are very scarce, although infection within these patients is not only associated with severe morbidity but also significantly higher mortality rates. Material and methods Retrospective study on 20 patients, who were operated on by a single experienced plastic and reconstructive surgeon within one year (June 2017-June 2018). The authors included all patients, who received microvascular transplants for reconstruction of soft tissue defects. Furthermore, age above 18 years and appropriate documentation allowing sufficient data collection were defined as inclusion criteria. The authors excluded all patients with perioperative systemic inflammation and transplant loss, as our aim was to solely determine and evaluate potential alterations of serological PCT levels after microsurgical interventions. Results The PCT cutoff level to differentiate physiological and pathological levels was defined as 0.1 μg/L. There was no detectable increase in procalcitonin in all of our 20 patients, for whom the authors performed microvascular transplantation to reconstruct soft tissue defects. Conclusion Serological PCT levels remain stable after the considered surgical interventions and therefore PCT levels might be utilized to identify systemic inflammation, thus helping to reduce severe complications by early individualized antiinfective treatment strategies.

OBJECTIVE: Size characterization of osteolytic jaw lesions (OJL), in particular of neoplastic nature, is heterogeneously performed and lacks standardization in the medical literature and clinical practice. An OJL’s volume holds promise as a surrogate for treatment response and prognosis. We comparatively evaluate various methods for size characterization of odontogenic OJLs. METHODS: We retrospectively performed semiautomatic image segmentation of CBCT data sets for volume approximation of neoplastic (51) and non-neoplastic odontogenic OJLs (100). We assessed the three greatest orthogonal diameters and calculated the volume using the cuboid- and ellipsoid-formula. Image segmentation was carried out using ITK-SNAP. Image segmentation-based volume approximation served as reference. Intra- and inter-rater variability were evaluated at hand of Bland–Altman-Analysis and dice similarity coefficient (DSC). RESULTS: Concerning the intrarater variability, we found the DSC to be highest for image segmentation-based volume approximation, simultaneously showing the tightest limits of agreement and greatest reliability. The cuboid formula showed consistent overestimation of the lesion’s volume with a percent mean difference of −52 % (upper and lower limits of agreement +8.57 % and −112.63%, respectively). In mean, the ellipsoid formula underestimated the lesion’s volume by 10.1% (upper and lower limits of agreement +76.8% and −56.6%, respectively). Inter rater variability was higher for formula-based volume approximation. Volume and multilocularity (p = 0.001) correlate with aggressiveness and growth potential. CONCLUSIONS: Segmentation-based volume approximation holds great promise for patient individualized treatment planning and clinical management. The data suggest that maximum tumour diameter-based size characterization, especially the cuboid-formula and the maximum diameter alone, should not be recommended.

Background This study aims at investigating the prognostic significance of lymph node ratio (LNR) in a cohort of patients with oral squamous cell carcinomas (OSCC), treated with neoadjuvant radiochemotherapy followed by radical surgery. Methods The study included 171 treatment-naive patients with biopsy-proven primary OSCC, being reviewed retrospectively. All patients received a concomitant neoadjuvant radiochemotherapy (RCT) followed by radical surgery of the primary tumor and neck dissection based on the pretreatment staging results. The Kaplan–Meier survival analysis method was used to estimate the events of interest for overall survival (OS). Prognostic factors were identified through univariate and multivariate analysis. Results The 5-year overall survival rate for all patients was 48 %. In univariate analysis, patient's age and data compiled from the histopathological examination as margin status, extracapsular spread, ypT, ypN, ypUICC, number of positive lymph nodes and lymph node ratio (LNR) had a statistically significant impact on overall survival. Multivariate analysis revealed an independent significant impact of patient age, ypT, margin status and LNR on OS. ypN showed no statistical significant impact on OS. Conclusion Our results show that LNR is an important predictor for OS in patients with OSCC that were treated with neoadjuvant radiochemotherapy and radical surgery.