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Wound healing is a complex biological process subject to complications that might jeopardize the patient's postoperative care. Appropriately approaching surgical wounds after head and neck surgery positively influences the quality and speed of wound healing and increases patient comfort. A large variety of dressing materials currently exist that allow the care of different types of wounds. Nevertheless, there is limited literature on the most suitable types of dressings after head and neck surgery. The objective of the present article is to review the most commonly used wound dressings, their benefits, indications, and disadvantages, and to provide a systematic approach for wound care within the head and neck. The Woundcare Consultant Society distinguishes wounds into three groups: black, yellow, and red. Each type of wound represents distinctive underlying pathophysiological processes with unique needs. Utilizing this classification along with the TIME model allows a proper characterization of wounds and the identification of potential healing barriers. This evidence-based and systematic approach can facilitate and guide the head and neck surgeon in selecting a wound dressing upon acknowledging their properties, which are herein reviewed and exemplified with representative cases.

Purpose: We aim to identify the dosimetric and clinical impact of reducing the total GTV-CTV-PTV margins in head-and-neck squamous cell carcinoma (HNSCC) treated with definitive (chemo)radiation. Materials and methods: The acute and late toxicity and outcomes of 155 consecutive patients treated between February 2017 and March 2019 with GTV-CTV-PTV margins of 9 mm were compared to those of 155 consecutive patients treated with total margin of 15 mm margin, before April 2015. All patients were treated with VMAT with daily-image guidance using CBCT. Results: Reducing the GTV-CTV-PTV by 6 mm resulted in significant reduction of total irradiated volume (PTV-total) by a median of 28.1% and significant reduction of doses to all salivary glands (largest reduction ipsilateral parotid gland; median −9.6 Gy) and constrictor muscle (−6.1 Gy) with subsequent reduction of the incidence of overall acute grade 3 toxicity (47.7% for 9 mm and 66.5% for 15 mm groups, p = 0.001), grade 3 mucositis (18.1% vs. 35.5%, p < 0.001) and feeding tube-dependency at the end of treatment (24.5% vs. 40%, p = 0.005). The incidence of late grade ≥ 2 xerostomia and dysphagia were also significantly lower in the 9 mm group (31.7% vs. 58.6% p < 0.001, and 15.4% vs. 26.7%, p = 0.04). The 2-year rates of loco-regional control, disease-free and overall survival were 78.8% vs.75.8%, 70.9% vs. 64.4%, and 83.8% vs. 67.6%, (p > 0.05, all). Conclusion: Reduction of the total GTV-CTV-PTV margins from 15 to 9 mm in HNSCC significantly reduced the irradiated volumes and the dose to salivary glands and constrictor muscle with significant reduction of radiation-related toxicity. The loco-regional control rates of both groups were comparable.

Psammomatoid ossifying fibroma (PsOF), also known as juvenile PsOF, is a benign fibro-osseous neoplasm predominantly affecting the extragnathic bones, particularly the frontal and ethmoid bones, with a preference for adolescents and young adults. The clinical and morphologic features of PsOF may overlap with those of other fibro-osseous lesions, and additional molecular markers would help increase diagnostic accuracy. Because identical chromosomal breakpoints at bands Xq26 and 2q33 have been described in 3 cases of PsOF located in the orbita, we aimed to identify the exact genes involved in these chromosomal breakpoints and determine their frequency in PsOF using transcriptome sequencing and fluorescence in situ hybridization (FISH). We performed whole RNA transcriptome sequencing on frozen tissue in 2 PsOF index cases and identified a fusion transcript involving SATB2, located on chromosome 2q33.1, and AL513487.1, located on chromosome Xq26, in one of the cases. The fusion was validated using reverse transcription (RT)-PCR and SATB2 FISH. The fusion lead to a truncated protein product losing most of the functional domains. Subsequently, we analyzed an additional 24 juvenile PsOFs, 8 juvenile trabecular ossifying fibromas (JTOFs), and 11 cemento-ossifying fibromas (COFs) for SATB2 using FISH and found evidence of SATB2 gene rearrangements in 58% (7 of 12) of the evaluable PsOF cases but not in any of the evaluable JTOF (n = 7) and COF (n = 7) cases. A combination of SATB2 immunofluorescence and a 2-color SATB2 FISH in our index case revealed that most tumor cells harboring the rearrangement lacked SATB2 expression. Using immunohistochemistry, 65% of PsOF, 100% of JTOF, and 100% of COF cases showed moderate or strong staining for SATB2. In these cases, we observed a mosaic pattern of expression with >25% of the spindle cells in between the bone matrix, with osteoblasts and osteocytes being positive for SATB2. Interestingly, 35% (8 of 23) of PsOFs, in contrast to JTOFs and COFs, showed SATB2 expression in

Background: Nontuberculous mycobacterial (NTM) cervicofacial lymphadenitis is a rare infection which almost exclusively occurs in children, most commonly children 0–5 years old. It can leave scars in highly visible areas. The present study aimed to evaluate the long-term esthetic outcome of different treatment modalities for NTM cervicofacial lymphadenitis. Methods: This retrospective cohort study included 92 participants with a history of bacteriologically proven NTM cervicofacial lymphadenitis. All patients were diagnosed at least 10 years prior and were aged >12 years upon enrollment. Based on standardized photographs, the scars were assessed by subjects with the Patient Scar Assessment Scale, and by five independent observers with the revised and weighted Observer Scar Assessment Scale. Results: The mean age at initial presentation was 3,9 years and the mean follow-up time was 15.24 years. Initial treatments included surgical treatment (n = 53), antibiotic treatment (n = 29) and watchful waiting (n = 10). Subsequent surgery was performed in two patients, due to a recurrence after initial surgical treatment, and in 10 patients initially treated with antibiotic treatment or watchful waiting. Esthetic outcomes were statistically significantly better with initial surgery, compared to initial non-surgical treatment, based on patient scores of scar thickness, and based on observer scores of scar thickness, surface appearance, general appearance and the revised and weighted sum score of all assessment items. Conclusions: The long-term esthetic outcome of surgical treatment was superior to non-surgical treatment. These findings could facilitate the process of shared decision making. Level of Evidence: Level III

Aims: Simple Bone Cysts (SBCs) predominantly occur in long bones and 59% harbour NFATC2 rearrangements. Jaw SBC is rare and was previously referred to as traumatic bone cyst. It can rarely occur in association with cemento-osseous dysplasia (COD). To determine whether jaw SBCs represent the same entity as SBC of the long bones, or if they have a different molecular signature, we collected 48 jaw SBC cases of 47 patients to assess NFATC2 rearrangement. Methods and results: Out of the 48 cases, 36 could be used for fluorescence in-situ hybridization (FISH), of which nine (two of which associated with COD) were successful using an NFATC2 split probe. The remaining cases failed to show adequate FISH signals. All nine cases lacked NFATC2 rearrangement and five of these showed no detectable gene fusions using Archer FusionPlex. Conclusion: In our study, NFATC2 rearrangement is absent in solitary jaw SBC (n = 7) and COD-associated SBC (n = 2). Our findings suggest that SBC presenting in the jaw is molecularly different from SBC in long bones. Future molecular studies may confirm the absence of clonal molecular aberrations in SBC of the jaw which would support a non-neoplastic, reactive origin.

Pleomorphic adenoma is the most common salivary gland tumor but is extremely rare in pediatric patients. The parotid gland is the most affected salivary gland, and the minor salivary glands are rarely affected. Here, we report a case of a 12-year-old boy with a pleomorphic adenoma of the palate.

Cementoblastomas are rare odontogenic tumors developing in close proximity to the roots of teeth. Due to their striking morphologic resemblance to osteoblastomas of the peripheral skeleton, we set out to determine whether cementoblastomas harbor the same FOS rearrangements with overexpression of c-FOS as has recently been described for osteoblastomas. In total, 16 cementoblastomas were analyzed for FOS expression by immunohistochemistry and for FOS rearrangements by fluorescence in situ hybridization (FISH). We observed strong and diffuse staining of c-FOS in 71% of cementoblastomas and identified a FOS rearrangement in all cases (n=3) applicable for FISH. In the remaining cases, FISH failed due to decalcification. Cementoblastomas harbor similar FOS rearrangements and show overexpression of c-FOS like osteoblastomas, suggesting that both entities might represent parts of the spectrum of the same disease.

In mandibular surgery, three-dimensionally printed patient-specific cutting guides are used to translate the preoperative virtually planned resection planes to the operating room. This study was performed to determine whether cutting guides are positioned according to the virtual plan and to compare the intraoperative position of the cutting guide with the resection performed. Nine patients were included. The exact positions of the resection planes were planned virtually and a patient-specific cutting guide was designed and printed. After surgical placement of the cutting guide, intraoperative cone beam computed tomography (CBCT) was performed. Postoperative CT was used to obtain the final resection planes. Distances and yaw and pitch angles between the preoperative, intraoperative, and postoperative resection planes were calculated. Cutting guides were positioned on the mandible with millimetre accuracy. Anterior osteotomies were performed more accurately than posterior osteotomies (intraoperatively positioned and final resection planes differed by 1.2 ± 1.0 mm, 4.9 ± 6.6°, and 1.8 ± 1.5°, respectively, and by 2.2 ± 0.9 mm, 9.3 ± 9°, and 8.3 ± 6.5° respectively). Differences between intraoperatively planned and final resection planes imply a directional freedom of the saw through the saw slots. Since cutting guides are positioned with millimetre accuracy compared to the virtual plan, the design of the saw slots in the cutting guides needs improvement to allow more accurate resections.

Purpose: 3D-printed cutting guides are the current standard to translate the virtual surgery plan to the intraoperative setting. The production of these patient-specific cutting guides is time-consuming and costly, and therefore, alternative approaches are currently subject of research. The aim of this study was to assess the accuracy and reproducibility of using a novel electromagnetic (EM) navigated surgical cutting guide to perform virtually planned osteotomies in mandible models. Methods: A novel 3D navigated cutting guide (dubbed Bladerunner) was designed and evaluated with a total of 20 osteotomies, performed on plaster mandibular models according to preoperative planning using EM navigation. The pre- and postoperative scans were registered, and the difference between the preoperatively planned osteotomy and the performed osteotomy was expressed as the distance between the planned and performed cutting planes, and the yaw and roll angles between the planes. Results: The mean difference in distance between the planned osteotomy and performed osteotomy was 1.1 mm (STD 0.6 mm), the mean yaw was 1.8° (STD 1.4°), and mean roll was 1.6° (STD 1.3°). Conclusion: The proposed EM navigated cutting guide for mandibular osteotomies demonstrated accurate positioning of the cutting plane according to the preoperative virtual surgical plan with respect to distance, yaw and roll angles. This novel approach has the potential to make the use of 3D-printed cutting guides obsolete, thereby decreasing the interval between diagnosis and surgery, reduce cost and allow for adaptation of the virtual plan in case of rapid tumor proliferation or unanticipated in situ deviations from the preoperative CT/MR imaging.

We wanted to find out whether ultrasound (US) can be used to assess the deep resection margins after excision of squamous cell carcinoma (SCC) of the tongue, as intraoperative feedback on their condition might help to prevent them being too close. Resected specimens of cancers of the tongue from 31 patients with SCC of the tongue were suspended in US gel and scanned with a small 5-10 MHz US probe. The tumour was readily visible and US could differentiate it from muscle tissue. The margin of normal tongue musculature surrounding the tumour was measured on the US images, and the minimal resection margin was noted and compared with that reported by the histopathologist. The mean (SD) deep resection margins measured on the US images differed by 1.1 (0.9) mm from those reported by the histopathologist (Pearson's correlation coefficient: 0.79, p < 0.01). The US measurements took a maximum of five minutes. It is feasible to use US to assess resection specimens of SCC of the tongue as an adjunct to existing strategies (such as frozen section analysis) to help achieve the desired deep surgical margins. The method is easy to incorporate into surgical routine as it does not take long.

Contains fulltext : 288341.pdf (Publisher’s version ) (Open Access) BACKGROUND: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). METHODS: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. RESULTS: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0-62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8-43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0-50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. CONCLUSION: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.

According to the WHO, mesenchymal tumours of the maxillofacial bones are subdivided in benign and malignant maxillofacial bone and cartilage tumours, fibro-osseous and osteochondromatous lesions as well as giant cell lesions and bone cysts. The histology always needs to be evaluated considering also the clinical and radiological context which remains an important cornerstone in the classification of these lesions. Nevertheless, the diagnosis of maxillofacial bone tumours is often challenging for radiologists as well as pathologists, while an accurate diagnosis is essential for adequate clinical decision-making. The integration of new molecular markers in a multidisciplinary diagnostic approach may not only increase the diagnostic accuracy but potentially also identify new druggable targets for precision medicine. The current review provides an overview of the clinicopathological and molecular findings in maxillofacial bone tumours and discusses the diagnostic value of these genetic aberrations.

Non-ossifying fibroma (NOF) and central giant cell granuloma (CGCG) are both benign tumours of bone with overlapping morphology and similar mutations in the RAS/MAPK pathway. However, NOF is located in the long bones with regression after puberty in contrast to CGCG which is located in the jaw bones and does not regress spontaneously. We hypothesised that endocrine regulation by oestrogen plays a role in the spontaneous regression in NOF. Therefore, we examined the expression of ERα in a series of NOF and CGCG. ERα expression (EP1) was determined using immunohistochemistry on 16 NOFs (whole slides), and 47 CGCGs (tissue microarrays (TMA’s n = 41 and whole slide n = 6)). As comparison, we included TMAs of other giant cell containing bone lesions: giant cell tumour of bone (n = 75), chondroblastoma (n = 12), chondromyxoid fibroma (n = 12), aneurysmal bone cyst (n = 6) and telangiectatic osteosarcoma (n = 6). All 16 NOF samples demonstrated ERα protein expression, while all 47 CGCG and all other giant cell containing bone tumours were negative. Most NOF samples had moderate staining intensity and between 24 and 49% of the spindle cells were ERα-positive. Our findings further support the role of endocrine regulation via oestrogen in the spontaneous regression in NOF. Whether oestrogen signalling at puberty is involved in the induction of senescence in the neoplastic cells of NOF harbouring RAS/MAPK pathway mutations needs further research. Since ERα expression was not observed in other giant cell containing bone lesions with overlapping morphological features, positive ERα expression may favour the diagnosis of NOF in challenging diagnostic cases.

© 2021 The AuthorThe majority of giant cell lesions of the jaw present as a solitary focus of disease in bones of the maxillofacial skeleton. Less frequently they occur as multifocal lesions. This raises the clinical dilemma if these should be considered distinct entities and therefore each need a specific therapeutic approach. Solitary giant cell lesions of the jaw present with a great diversity of symptoms. Recent molecular analysis revealed that these are associated with somatic gain-of-function mutations in KRAS, FGFR1 or TRPV4 in a large component of the mononuclear stromal cells which all act on the RAS/MAPK pathway. For multifocal lesions, a small group of neoplastic multifocal giant cell lesions of the jaw remain after ruling out hyperparathyroidism. Strikingly, most of these patients are diagnosed with jaw lesions before the age of 20 years, thus before the completion of dental and jaw development. These multifocal lesions are often accompanied by a diagnosis or strong clinical suspicion of a syndrome. Many of the frequently reported syndromes belong to the so-called RASopathies, with germline or mosaic mutations leading to downstream upregulation of the RAS/MAPK pathway. The other frequently reported syndrome is cherubism, with gain-of-function mutations in the SH3BP2 gene leading through assumed and unknown signaling to an autoinflammatory bone disorder with hyperactive osteoclasts and defective osteoblastogenesis. Based on this extensive literature review, a RAS/MAPK pathway activation is hypothesized in all giant cell lesions of the jaw. The different interaction between and contribution of deregulated signaling in individual cell lineages and crosstalk with other pathways among the different germline- and non-germline-based alterations causing giant cell lesions of the jaw can be explanatory for the characteristic clinical features. As such, this might also aid in the understanding of the age-dependent symptomatology of syndrome associated giant cell lesions of the jaw; hopefully guiding ideal timing when installing treatment strategies in the future.

The purpose of this study was to evaluate the feasibility of electromagnetic (EM) navigation for guidance on osteotomies in patients undergoing oncologic mandibular surgery. Preoperatively, a 3D rendered model of the mandible was constructed from diagnostic computed tomography (CT) images. Cutting guides and patient specific reconstruction plates were designed and printed for intraoperative use. Intraoperative patient registration was performed using a cone beam CT scan (CBCT). The location of the mandible was tracked with an EM sensor fixated to the mandible. The real-time location of both the mandible and a pointer were displayed on the navigation system. Accuracy measurements were performed by pinpointing four anatomical landmarks and four landmarks on the cutting guide using the pointer on the patient and comparing these locations to the corresponding locations on the CBCT. Differences between actual and virtual locations were expressed as target registration error (TRE). The procedure was performed in eleven patients. TREs were 3.2 ± 1.1 mm and 2.6 ± 1.5 mm using anatomical landmarks and landmarks on the cutting guide, respectively. The navigation procedure added on average half an hour to the duration of the surgery. This is the first study that reports on the accuracy of EM navigation in patients undergoing mandibular surgery.

Purpose Information on long-term treatment outcome for nontuberculous mycobacterial (NTM) cervicofacial lymphadenitis in children is scarce. The purpose of this study is to evaluate long-term outcome for surgical treatment, which is the mainstay treatment modality. Methods This case series describes recurrence rates of surgically treated NTM cervicofacial lymphadenitis patients with a follow-up of at least 10 years. The current study data were partially collected from a randomized, prospective, multicenter, multidisciplinary trial (CHIMED study), which was conducted between 2000 and 2006 to determine the optimal treatment for NTM cervicofacial lymphadenitis in children. After the CHIMED trial inclusion ended, our institute continued to serve as a referral center. This enabled us to enlarge the surgical CHIMED cohort by adding patients who were treated during 2007 to 2010 in our center and collect the rest of the current study data. Results About 427 children with chronic cervicofacial lymphadenopathy were analyzed. Among these, 290 had microbiologically confirmed cervicofacial mycobacterial infections (n = 3 Mycobacterium tuberculosis, n = 1 Mycobacterium bovis, n = 286 NTM). Of these 286 children with NTM cervicofacial lymphadenitis, 189 were treated surgically (median age: 41 months, range: 9-144, 46.0% males). The affected lymph nodes were excised in 151 children (79.9%), and curettage was performed in 38 children (20.1%). One patient (0.07%) experienced a reactivation/recurrence 2 years after surgical excision and required another surgical excision. Three children (7.9%) experienced infection reactivation/recurrences after curettage, confirmed by redness or a draining fistula, within the first year after healing. Two of these 3 patients were treated with additional surgical excisions. Conclusion The long-term outcome of surgical excision for NTM cervicofacial lymphadenitis is favorable with a low recurrence rate. Curettage or a conservative wait-and-see approach can be considered an alternative in advanced and surgically challenging cases. However, healing will take longer, and late recurrences are possible.

Purpose: A dental splint was developed for non-invasive rigid point-based registration in electromagnetically (EM) navigated mandibular surgery. Navigational accuracies of the dental splint were compared with the common approach, that is, using screws as landmarks. Methods: A dental splint that includes reference registration notches was 3D printed. Different sets of three points were used for rigid point-based registration on a mandibular phantom: notches on the dental splint only, screws on the mandible, contralateral screws (the side of the mandible where the sensor is not fixated) and a combination of screws on the mandible and notches on the dental splint. The accuracy of each registration method was calculated using 45 notches at one side of the mandible and expressed as the target registration error (TRE). Results: Average TREs of 0.83 mm (range 0.7–1.39 mm), 1.28 mm (1.03–1.7 mm), 2.62 mm (1.91–4.0 mm), and 1.34 mm (1.30–1.39 mm) were found, respectively, for point-based registration based on the splint only, screws on the mandible, screws on the contralateral side only, and screws combined with the splint. Conclusion: For dentate patients, rigid point-based registration performs best utilizing a dental splint with notches. The dental splint is easy to implement in the surgical, and navigational, workflow, and the notches can be pinpointed and designated on the CT scan with high accuracy. For edentate patients, screws can be used for rigid point-based registration. However, a new design of the screws is recommended to improve the accuracy of designation on the CT scan.

In patients with non-tuberculous mycobacterial cervicofacial lymphadenitis, incomplete surgical removal of infected lymph nodes leads to delayed healing and a higher recurrence rate, with eventual spontaneous drainage through the skin. However, complete surgical removal is not always achievable due to the extent of the infected tissue and proximity to vulnerable structures, such as the facial or accessory nerve. The aim of this study was to identify the clinical determinants of the (in)ability to perform complete surgical removal. The electronic health records of patients aged 0–15 years with bacteriologically proven non-tuberculous mycobacterial cervicofacial lymphadenitis, who underwent surgical treatment and preoperative sonographic imaging, were analysed. This was a case–control study. A total of 103 patients met the inclusion criteria. Most of the infections were unilateral, submandibular, and caused by Mycobacterium avium. Multiple logistic regression analysis revealed that higher age (odds ratio 1.24, 95% confidence interval 1.04–1.47) and fistulization (odds ratio 3.15, 95% confidence interval 1.13–8.75) were significantly associated with a limited ability to surgically remove all infected tissue. However, a larger sonographic lymph node size was not significantly associated. These findings could aid clinicians when informing the parent(s)/guardian(s) of the patient preoperatively and in properly estimating the intraoperative and postoperative course.

Background: Photodynamic therapy (PDT) is a promising treatment option for recurrent sinonasal malignancies. However, light administration in this area is challenging given the complex geometry, varying tissue optical properties and difficult accessibility. The goal of this study was to estimate the temporal and spatial variation in fluence and fluence rate during sinonasal mTHPC-mediated PDT. It was investigated whether the predetermined aim to illuminate with a fluence of 20 J⋅cm−2 and fluence rate of 100 mW⋅cm−2 was achieved. Methods: In eleven patients the fluence and fluence rates were measured using in vivo light dosimetry at the target location during real-time sinonasal PDT. There was a variance in sinonasal target location and type of light diffuser used. In four patients two isotropic detectors were used within the same cavity. Results: All measurements showed major fluence rate fluctuations within each single isotropic detector probe over time, as well as between probes within the same cavity. The largest fluence rate range measured was 328 mW⋅cm−2. Only one probe showed a mean fluence rate of ∼100 mW⋅cm−2. Taken all probes together, a fluence rate above 80 mW⋅cm−2 was measured in 31 % of the total light exposure; in 22 % it was less than 20 mW⋅cm−2. Thirty-three percent showed a fluence of at least 20 J⋅cm−2. Conclusions: The current dosimetry approach for sinonasal intra-cavity PDT shows major temporal and spatial variations in fluence rate and a large variance in light exposure time. The results emphasize the need for improvement of in vivo light dosimetry and dosimetry planning.

Previous dosimetric studies during photodynamic therapy (PDT) of superficial lesions within a cavity such as the nasopharynx, demonstrated significant intra- and interpatient variations in fluence rate build-up as a result of tissue surface re-emitted and reflected photons, which depends on the optical properties. This scattering effect affects the response to PDT. Recently, a meta-tetra(hydroxyphenyl)chlorin-mediated PDT study of malignancies in the paranasal sinuses after salvage surgery was initiated. These geometries are complex in shape, with spatially varying optical properties. Therefore, preplanning and in vivo dosimetry is required to ensure an effective fluence delivered to the tumor. For this purpose, two 3D light distribution models were developed: first, a simple empirical model that directly calculates the fluence rate at the cavity surface using a simple linear function that includes the scatter contribution as function of the light source to surface distance. And second, an analytical model based on Lambert's cosine law assuming a global diffuse reflectance constant. The models were evaluated by means of three 3D printed optical phantoms and one porcine tissue phantom. Predictive fluence rate distributions of both models are within +/- 20% accurate and have the potential to determine the optimal source location and light source output power settings.

Bloom syndrome is an autosomal recessive condition characterized by severe pre- and postnatal growth deficiency, immunodeficiency, an increased risk for malignancies, craniofacial dysmorphisms, and "typical" erythematous sun-sensitive skin lesions of the face. This facial rash has a butterfly-shaped distribution around the nose and is usually observed for the first time during the early years of life. Though reported as being a main feature of Bloom syndrome, there seems to be phenotypic variability regarding this facial skin rash among patients. It has been previously reported that in some individuals with Bloom syndrome these sun-sensitive lesions are less prominent or even absent. In this report we describe a 36 year old woman with short stature, microcephaly, several dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months after her consultation at the department of Clinical Genetics. Whole Exome Sequencing demonstrated that she had Bloom syndrome caused by a compound heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome does not always present with erythematous sun-sensitive skin lesions of the face. We would like to underline that phenotypic variation regarding this "hallmark" feature of Bloom syndrome exists. Being aware of this might prevent a delay in diagnosing this rare short-stature syndrome and, subsequently, its potential clinical implications.

Objective In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the clinical benefit of PDT as adjuvant therapy next to surgery with positive resection margins. The role of the time interval between surgery and PDT on survival outcomes also was investigated. Study design Retrospective cohort analysis. Methods Adjuvant PDT was performed in patients with a malignancy in the head and neck region with close or positive resection margins who were not eligible for conventional treatment options. The primary endpoint was progression-free survival. Secondary endpoints were disease-free survival, overall survival, and optimal time interval between surgery and PDT. Results Fifty-four patients were treated with surgery followed by meta-tetrahydroxyphenylchlorin-mediated PDT. There was a large diversity in tumor location and histopathology, as well as in time interval between surgery and PDT. The 2-year progression-free survival rate was 30%; 2-year disease-free survival rate was 28%; and 2-year overall survival was 51%. Disease-free survival was significantly better when the time interval between surgery and PDT was ≥ 6 weeks (P = 0.02). Conclusion PDT can be applied as adjuvant therapy after surgery in cases of a malignancy with close or positive tumor resection margins. However, the clinical benefits are yet to be determined. There is a significantly better disease-free survival with a time interval between surgery and PDT of minimal 6 weeks. Level of evidence 4. Laryngoscope, 128:657-663, 2018.

Purpose: This is a retrospective cohort study of patients with a central giant cell granuloma (CGCG) treated at a single center to assess and compare the different surgical and non-surgical approaches. Material and methods A cohort with a single histologically proven non-syndrome-related CGCG was selected and reviewed. Patients were allocated to group I (surgery), group II (pharmacotherapy), and group III (pharmacotherapy and surgery). The primary outcome was long-term radiologic response using computed tomography. Secondary outcomes were intermediate radiologic responses and occurrence and severity of side effects. Results Thirty-three subjects were included in the study. The surgical group (n = 4) included 1 patient with progression during follow-up and a relatively high post-surgical morbidity. Twenty-nine patients started on various pharmacological treatment regimens (groups II and III). Fourteen patients could be managed without additional surgery. One of these lesions showed progression during follow-up. The other 15 lesions underwent additional surgery, and none showed progression during follow-up. Interferon treatment was associated with the most side effects.Conclusion Pharmacological agents have a role in the treatment of aggressive and non-aggressive CGCGs by limiting the renewed progression during long-term follow up and the extent and morbidity of surgical treatment.

Purpose To document long-term outcomes using a standardized treatment protocol of enucleation with preservation of vital structures and adjuvant subcutaneous interferon for aggressive giant cell lesions (GCLs) of the jaws. Materials and Methods A retrospective cohort study was designed. We evaluated all patients treated at Massachusetts General Hospital from April 1995 through September 2015 by enucleation with preservation of vital structures and adjuvant daily subcutaneous interferon for aggressive GCLs. The sample included patients with complete medical records consisting of clinical, radiographic, histopathologic, and follow-up data. The exclusion criteria included patients with incomplete records, contraindications to interferon therapy, non-aggressive GCLs, and GCLs associated with syndromes or with hyperparathyroidism. The primary outcome variable was long-term progression-free survival (PFS). The secondary outcome variables were adverse effects and laboratory abnormalities classified by type, frequency, and severity. Predictor variables for recurrence or failure included age, gender, location and features of lesion, type of procedure, duration of interferon treatment, amount of bone fill at end of treatment, and adverse effects. Descriptive statistics, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were computed. Results Of a total of 77 patients, 45 (mean age, 18.8 ± 12.5 years; 29 female patients; 36 in whom the mandible was affected) met the inclusion criteria. The mean duration of interferon therapy was 7.9 ± 2.3 months. After follow-up of 4.8 ± 3.9 years, 6 patients showed progression of the lesion, considered recurrence (13.3% failure rate, 82.6% PFS rate). Most patients had mild (n = 42; 93.3%) and/or moderate (n = 31; 68.8%) side effects, which were readily managed. Adverse effects required stoppage of interferon in 7 patients, whereas no patients had long-term toxicity. No variable was significantly associated with PFS. Conclusions The results of this study indicate that enucleation with preservation of vital structures in combination with adjuvant interferon alfa is a reliable treatment for aggressive GCLs of the jaws associated with a low recurrence rate.

Background The majority of patients with head and neck squamous cell carcinoma (HNSCC) receive bilateral elective nodal irradiation (ENI), in order to reduce the risk of regional failure. Bilateral ENI, as compared to unilateral ENI, is associated with higher incidence of acute and late radiation-induced toxicity with subsequent deterioration of quality of life. Increasing evidence that the incidence of contralateral regional failure (cRF) in lateralized HNSCC is very low ( Methods In this one-armed, single-center prospective trial, patients with primary T1-4 N0-2b HNSCC of the oral cavity, oropharynx, larynx (except T1 glottic) or hypopharynx, not extending beyond the midline and planned for primary (chemo) radiotherapy, are eligible. After 99mTc-nanocolloid tracer injection in and around the tumor, lymphatic drainage is visualized using SPECT/CT. In case of contralateral lymph drainage, a contralateral sentinel node procedure is performed on the same day. Patients without contralateral lymph drainage, and patients with contralateral drainage but without pathologic involvement of any removed contralateral sentinel nodes, receive unilateral ENI. Only when tumor cells are found in a contralateral sentinel node the patient will be treated with bilateral ENI. The primary endpoint is cumulative incidence of cRF at 1 and 2 years after treatment. Secondary endpoints are radiation-related toxicity and quality of life. The removed lymph nodes will be studied to determine the prevalence of occult metastatic disease in contralateral sentinel nodes. Discussion This single-center prospective trial aims to reduce the incidence and duration of radiation-related toxicities and improve quality of life of HNSCC patients, by using lymph drainage mapping by SPECT/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation. Trial registration ClinicalTrials.gov Identifier: NCT03968679, date of registration: May 30, 2019.

Background: Cutaneous squamous cell carcinoma (cSCC) is a common type of malignant skin disorder. An uncommon feature is local bony invasion, as can rarely be seen in lesions on the scalp. The optimal treatment strategy in these rare cases is still under debate. Objective: The aim of this case report is to present a 1-stage three-dimensional planned surgical resection and reconstruction of a cSCC with bony invasion into the scalp and to discuss the alternative options and potential pitfalls. Materials and methods: A patient diagnosed with rT4N0M0 cSCC of the scalp underwent a cranial resection and reconstruction in 1 stage. With the use of computer-assisted design and computer-assisted manufacturing a patient-specific implant (PSI) of poly (ether ether ketone) was manufactured. After the PSI was inserted, it was covered with a latissimus dorsi muscle and a split-thickness skin graft. Results: Intraoperatively the resection template generated an accurate resection and accurate and fast placement of the PSI. The reconstruction had a clinical satisfactory esthetic result, but was hampered by the development of a small wound dehiscence was observed over the postoperative course. Conclusion: Three-dimensional planned resection and reconstruction for composite defects of the skull after resection of a cSCC of the scalp with bony invasion may lead to an accurate and predictable resection and accurate and fast placement of the PSI. However, patient specific characteristics should be considered to assess potential risks and benefits before opting for this one-stage treatment strategy.

Highlights • Contralateral regional failure still occurs after bilateral nodal irradiation. • No significant predictive factors were identified for contralateral regional failure. • Overall survival did not differ between patients with ipsi- or contralateral failure., Background The vast majority of patients with head and neck squamous cell carcinoma (HNSCC) routinely undergo elective nodal irradiation (ENI) to both sides of the neck. Little is known about the extent to which bilateral ENI prevents regional failure (RF) and contralateral RF (cRF) in particular, while such knowledge is necessary to evaluate the results of more selective approaches like unilateral ENI. We investigated the rate and pattern of RF after bilateral ENI, the rate of cRF in the electively irradiated contralateral neck, and tried to identify risk factors for development of cRF. Materials and methods Retrospective cohort study of a consecutive series of 605 patients with T1-4N0-3 HNSCC treated between 2008 and 2017 with primary (chemo)radiation and bilateral ENI. Results Median follow-up was 43 months (range 1.4–126). Three-year cumulative incidence of RF was 12.7%. Three-year cumulative incidences of ipsilateral RF (iRF) and cRF were 10.6% and 2.8%, respectively. All cRF occurred within the electively treated volume. Salvage treatment was possible in 65% and 59% of patients with iRF and cRF, respectively (p = 0.746). The 3-year overall survival rates after RF in patients with iRF and cRF were 27.4% and 41.2%, respectively (p = 0.713). Three-year cancer-specific survival rates were 31.6% and 48.1%, respectively (p = 0.634). In multivariate analysis, no significant predictive factors were identified for cRF after bilateral ENI. Conclusion Contralateral regional failure is rare, but still occurs in 2.8% of patients treated with bilateral ENI. The possibilities for salvage treatment, the rates of overall survival and cancer-specific survival were comparable to patients with iRF.

To investigate the feasibility of lymph drainage mapping (LDM) using SPECT/CT to help select head and neck cancer (HNSCC) patients for unilateral elective neck irradiation (ENI). Patients with lateralized HNSCC treated with radiotherapy routinely undergo bilateral ENI, despite the incidence of contralateral regional failure being relatively low even after unilateral ENI. We hypothesized that patients with a lateralized tumor without visible lymph drainage to the contralateral neck have an extremely low risk of contralateral involved nodes. Excluding the contralateral neck from elective irradiation will reduce radiation-induced toxicity and improve quality-of-life. Fifty-five patients with lateralized cT1-3N0-2bM0 HNSCC not crossing the midline underwent LDM. Radiolabeled 99mTc-nanocolloid was injected in 4–5 depots around and in the primary tumor. Lymph drainage patterns were visualized using planar scintigraphy and SPECT/CT after 4 h. We report on the incidence of contralateral drainage, the location of draining areas, and the size of underlying nodes. Lymphatic drainage was successfully visualized in 54 patients (98%). In 11 patients (20%) with visible contralateral drainage, 14 draining areas (16 nodes; median volume 0.50 cc, diameter 8.0 mm) were identified. Neck levels with contralateral drainage were level II (88%), III (25%), and IV (13%). Contralateral drainage was significantly higher in T3 compared to T1–2 tumors (45 and 14%, respectively, P = 0.035). SPECT/CT-guided LDM is feasible and can be used to guide unilateral ENI in HNSCC patients in prospective studies. In addition, the anatomical confidence in visualization of contralateral drainage indicates a potential for ENI limited to draining levels alone.

In this research project the outcomes of photodynamic therapy for the treatment of stage I and II carcinoma of the lip are presented. Retrospectively, 15 patients diagnosed with a primary stage I or II lip carcinoma and treated with meta-tetra hydroxyphenyl chlorin mediated photodynamic therapy were evaluated. The primary outcome measure was disease free survival; the secondary outcome measure was the functional and aesthetic outcome after treatment. A total of 16 primary lip carcinomas were evaluated (75% stage I; 25% stage II). In 94% of the primary lip carcinomas, photodynamic therapy led to a complete remission after a variable follow-up of 14 months to 11 years. The functional and aesthetic long-term outcomes were considered excellent. Photodynamic therapy for the treatment of stage I and II lip carcinoma has a disease free survival rate comparable to surgery or radiotherapy and has outstanding functional and aesthetic outcomes.De mond voorspoelen met water of poetsen met een droge tandenborstel, draagt niet bij aan een verbeterde tandplaque verwijdering bij het tandenpoetsen. Ook poetsen volgens een specifieke poetsvolgorde draagt daaraan niet bij. Spoelen met water of water drinken heeft een direct effect op de slechte ochtendadem. De combinatie van tandenpoetsen, tong reinigen en een mondspoelmiddel laat na 24 uur een effect zien op de slechte ochtendadem ten opzichte van alleen poetsen met tandpasta. Het gebruik van een mondspoelmiddel met de specifieke ingrediënten chloorhexidine en essentiële oliën, heeft een positief effect op de reductie van gingivitis. Het gebruik van vergelijkbare mondspoelmiddelen als koelvloeistof in ultrasone apparatuur heeft geen toegevoegd effect op het behandelresultaat bij parodontitispatiënten. Water is een effectieve koelvloeistof.

Background This is a review of the management considerations regarding exodontia for patients taking antithrombotic medications that affect platelet function or aggregation. Methods The authors reviewed the literature, focusing on the indications and mechanisms of antiplatelet therapy and the perioperative management of patients taking these agents who require exodontia or other dentoalveolar surgery. Results Dentists making management decisions regarding patients taking antiplatelet therapy should consider the patient’s risk of experiencing perioperative hemorrhage against the risk of experiencing complications associated with thromboembolic events. The risk of perioperative bleeding complications is low for patients taking single or dual antiplatelet therapy. Intraoperative and postoperative bleeding can be controlled with local hemostatic measures. Conclusion For patients taking antiplatelet medication, bleeding risk for exodontia is generally lower than the risk of experiencing thromboembolic events owing to cessation of therapy. Practical Implications Dentists can safely complete exodontia in patients who continue taking antiplatelet therapy. The dentist should consult the patient’s prescribing physician before considering altering the patient’s antiplatelet therapy regimen.

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.

A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. This is the second reported NSML patient with MGCL. Our case adds to the assumption that, despite a different molecular pathogenesis and effect on the RAS/MEK pathway, NSML shares the development of MGCL, with other RASopathies.

ObjectiveThe aim of this study is to analyze the craniofacial morphology in patients with unrepaired isolated cleft palate (UICP) at childhood, adolescence and adulthood, in order to assess the influence of nonsurgical factors on the craniofacial growth in these patients.Material and methodsLateral and posteroanterior cephalograms of 106 non-syndromic UICP patients and 102 normal matched controls were obtained and analyzed. Patients and controls were divided into three subgroups: children (5-7 years), adolescents (12-14 years), and adults (>18 years).ResultsUICP patients in childhood showed a shortened cranial basal length; reduced bony nasopharyngeal height; short maxillary depth and height with a posterior positioned maxilla and an increased width of the nasal cavity, maxilla and orbit; and a shortened mandibular length and height. UICP patients in adulthood showed a normal nasopharyngeal and mandibular morphology. However, the patients in this subgroup still showed a shortened cranial basal length, and short maxillary depth and anterior height with increased width of the nasal cavity, maxilla and orbit.ConclusionsCraniofacial morphology and growth in patients with UICP were significantly affected by nonsurgical factors. Growth of the cranial base and upper face were absolutely reduced, while growth of the bony nasopharynx and mandible were only postponed.

Immunostaining revealed the presence of KLK 3, 4, 9 & 11 in all tissue types studied. KLK 5 was present only in KOT’s (p

Purpose. It is assumed that osteosarcomas of the jaws mainly occur at older ages, whereas the most prominent sites, that is, the long bones, are more affected at ages Patients and Methods. This study analyses the nationwide data of the Dutch Cancer Registry on osteosarcoma during the period from 1991 to 2010. Age-corrected incidence rates were calculated.Results. In 949, 38 patients had tumors in the maxilla and in 58 in the mandible. Median age for maxilla, mandible, and other localizations was 45.5, 49, and 23 years, respectively. Age-corrected incidence for osteosarcomas increased after a steep decline for the age cohorts from 20 to 60 years to nearly the same level as the younger patients. The incidence for maxillary lesions showed a steady increase from 0.46 to 1.60 per million over all age ranges; the highest incidence for mandibular lesions was found in the age cohort from 60 to 79 years. In respect to histology, no shifts for age were found, except for Paget’s disease-related osteosarcoma. In older patients, chemotherapy was omitted more often. Overall survival was similar for all age groups, except for extragnatic tumor patients in the age range of 60–79 years.Conclusions. Osteosarcomas have comparable incidences below the age of 20 as compared with ages >60 years. Poorer outcome in older people is likely due to refraining from chemotherapy.