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Purpose: To investigate the pathobiological origin of local relapse after chemoradiotherapy, we studied genetic relationships of primary tumors (PT) and local relapses (LR) of patients treated with chemoradiotherapy. Experimental Design: First, low-coverage whole genome sequencing was performed on DNA from 44 biopsies of resected head and neck squamous cell carcinoma (HNSCC) specimens (median 3 biopsies/tumor) to assess suitability of copy number alterations (CNAs) as biomarker for genetic relationships. CNAs were compared within and between tumors and an algorithm was developed to assess genetic relationships with consideration of intratumor heterogeneity. Next, this CNA-based algorithm was combined with target enrichment sequencing of genes frequently mutated in HNSCC to assess the genetic relationships of paired tumors and LRs of patients treated with chemoradiotherapy. Results: Genetic relationship analysis using CNAs could accurately (96%) predict tumor biopsy pairs as patient-matched or independent. However, subsequent CNA analysis of PTs and LRs after chemoradiotherapy suggested genetic relationships in only 20% of cases, and absence in 80%. Target enrichment sequencing for mutations confirmed absence of any genetic relationship in half of the paired PTs and LRs. Conclusions: There are minor variations in CNA profiles within different areas of HNSCC tumors and many between independent tumors, suggesting that CNA profiles could be exploited as a marker of genetic relationship. Using CNA profiling and mutational analysis of cancer driver genes, relapses after chemoradiotherapy appear to be partially genetically related to the corresponding PTs, but seem often genetically unrelated. This remarkable observation warrants further studies and will impact therapeutic innovations and prognostic modeling when using index tumor characteristics.

De diagnose arteriitis temporalis is soms lastig te stellen omdat de klachten kunnen variëren, in intensiteit wisselen en niet altijd karakteristiek zijn. De aandoening is een craniale uiting van reuscelarteriitis met aantasting van grote en middelgrote arteriën. De eerste uiting van arteriitis temporalis kan een pijnklacht in de tong zijn zonder afwijkingen bij klinisch onderzoek. Soms is in een later stadium sprake van ulceratie of necrose van een deel van een tonghelft . Andere symptomen kunnen nieuw ontstane hoofdpijn, kaakclaudicatie en acuut visusverlies zijn. Om de diagnose arteriitis temporalis te stellen wordt histologisch onderzoek verricht van een biopt, genomen van de arteria temporalis. Behandeling bestaat uit langdurig gebruik van corticosteroïden. Bij patiënten met enkelzijdige onverklaarbare pijn in een klinisch niet afwijkende tong of een ulcus op de tong zonder direct aanwijsbare oorzaak, kan sprake zijn van arteriitis temporalis.

Background: To investigate if depth of invasion (DOI) can predict occult nodal disease in patients with cT1‐2N0 (7th TNM) oral squamous cell carcinoma (OSCC) staged by sentinel lymph node biopsy (SLNB).Methods: In 199 OSCC patients, DOI measurements and SLNB were performed.Results: Metastases were found in 64 of 199 patients (32%). Of these 64 patients, the mean DOI was 6.6 mm compared to 4.7 mm in patients without metastases (P = .003). The ROC‐curve showed an area under the curve of 0.65 with a most optimal cutoff point of 3.4 mm DOI (sensitivity 83% and specificity 47%). Regional metastases were found in 15% of patients with DOI ≤ 3.4 mm.Conclusion: DOI seems to be a poor predictor for regional metastasis in patients with cT1‐2N0 OSCC. Therefore, staging of the neck using SLNB in patients with early stage oral cancer should also be performed in tumors with limited DOI and probably in T3 (8th TNM) OSCC ≤4 cm diameter.

RATIONALE: This study evaluates the lymphatic drainage patterns and determines the accuracy of the sentinel lymph node biopsy (SLNB) in patients diagnosed with a cT1-2N0 OSCC and a history of neck surgery or radiotherapy in three Dutch head and neck centers.MATERIALS AND METHODS: Retrospective analysis of 53 cT1-2N0 OSCC patients, who underwent SLNB between 2007 and 2016, after a history of neck surgery or radiotherapy. Ten patients had previous treatment of the neck only contralateral from the current tumour. These ten patients were not used for the analysis of lymphatic drainage patterns. The 43 patients with previous ipsilateral or bilateral treatment of the neck had a history of ipsilateral SLN extirpation (n = 9; 21%), neck dissection (n = 16; 37%), radiotherapy (n = 10; 23%), or combined neck dissection and radiotherapy (n = 8; 19%).RESULTS: SLNs were detected in 45 patients, resulting in an identification rate of 85% (45/53). Three patients (7%) had at least one positive SLN. One patient (1/45; 2%) was diagnosed with regional recurrence during the follow-up after a negative SLNB (sensitivity 75%, negative predictive value 98%). The first SLN was detected in level I-III in 58% of the patients, unexpected drainage patterns were observed in 30% (first SLN level IV 9% and level V 5% and contralateral neck in well-lateralized tumours 16%). In 12% no lymphatic drainage pattern was visible.CONCLUSIONS: SLNB seems to be a reliable procedure for neck staging of cT1-2N0 OSCC patients with a previously treated neck. SLNB determines the individual lymphatic drainage patterns, enabling visualization of unexpected drainage pattern variability in 30% of these patients.

Head and neck squamous cell carcinomas (HNSCC) develop in fields of genetically altered cells. These fields are often dysplastic and a subset can be recognized as (erythro)leukoplakia, but most are macroscopically invisible. There is a lack of adequate treatment options to eradicate these fields, whereas they underlie the development of primary tumors as well as part of the local relapses. Unfortunately, there are almost no representative cellular models available to identify suitable treatment options. To this end, clinical biopsy specimens (n = 98) were cultured from normal appearing mucosa of the surgical margins of patients with primary HNSCCs (n = 32) to generate precancer cell culture models. This collection was extended with six previously established precancer cell cultures. Genetic analysis was performed on cultures with an extended life span (≥20 population doublings), the previously established cultures, and some randomly selected cultures. In total, cancer-associated changes were detected in 18 out of 34 (53%) cultures analyzed, which appeared to be independent of life span. A variety of genetic changes were identified, including somatic mutations as well as chromosomal copy-number aberrations (CNA). Loss of CDKN2A/p16Ink4A and mutations in TP53/p53 were most prominent. Remarkably, in some of these precancer cell cultures only chromosomal CNAs were detected, and none of the frequently occurring driver mutations. Implications: The precancer cell cultures, characterized herein, form a representative collection of field models that can be exploited to identify and validate new therapeutic strategies to prevent primary HNSCCs and local relapses.

There is a distinct lack of uniformity in the definitions and clinical terminologies related to oral leukoplakia and leukoplakialike lesions and disorders. Proposals have been put forward to subclassify leukoplakia into a homogeneous and a non-homogeneous type based on color only, being either predominantly white or mixed white-and-red, respectively, irrespective of the texture of the lesion. In this proposal there is no need anymore to regard the poorly defined proliferative verrucous leukoplakia as a separate entity. Since keratosis is primarily a histopathological term, its clinical use is discouraged. Alternative terminology for these so-called keratotic lesions and disorders has been put forward. Finally, a suggestion has been made to rename the term hairy leukoplakia, being a well defined, not potentially malignant disorder particularly related to HIV-infection, into 'EBV-positive white lesion of the tongue' (EBVposWLT). Key words:Potentially malignant oral disorders, oral leukoplakia, oral keratosis, hairy leukoplakia.

Objectives: The aim of this study was to investigate whether the extent of mandibular resorption and gender is related to the bone turnover and microarchitecture of the edentulous mandible. Participants and methods: A mandibular bone sample was obtained at canine position from 36 edentulous participants (50% women; mean age: 65 years) during dental implant surgery. All female participants were postmenopausal. Mandibular height, duration of edentulous state and resorption pattern (Cawood classification) were recorded. Microcomputed tomography was used to determine bone mineral density, bone volume fraction, trabecular connectivity density, trabecular number, trabecular thickness and trabecular separation. Histomorphometric analysis was used to assess bone turnover: osteoid area and surface were measured as a parameter for bone formation and osteoclast numbers were determined as a parameter for bone resorption. Correlations between micro-CT, histomorphometrical parameters and clinical data were analysed with correlation coefficients and parametric and non-parametric tests. Results: Lower mandibular height was strongly associated with higher bone mineral density in trabecular bone. Women showed higher osteoclast numbers in trabecular bone than men. In trabecular bone of women, bone volume was significantly related to osteoclast numbers, osteoid surface and osteoid area. Conclusions: The higher trabecular bone mineral density found in the edentulous mandible could either indicate a restructuring process of the resorbed mandible or suggests that the inferior region of the mandible is more highly mineralised. In women, higher bone turnover is associated with lower bone volume, suggesting an effect of postmenopausal oestrogen deficiency on bone turnover in the edentulous mandible.

During inflammation of the gums, resident cells of the periodontium, gingival fibroblasts (GFs), interact with heterogeneous cell populations of the innate and adaptive immune system that play a crucial role in protecting the host from pathogenic infectious agents. We investigated the effects of chronic inflammation, by exposing peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocyte (PBL) cultures, and GF&ndash, PBMC cocultures to Toll-like receptor 2 (TLR2) and TLR4 activators for 21 days and assessed whether this influenced leukocyte retention, survival, and proliferation. Chronic stimulation of PBMC&ndash, GF cocultures with TLR2 and TLR4 agonists induced a reduction of NK (CD56+CD3&minus, ), T (CD3+), and B (CD19+) cells, whereas the number of TLR-expressing monocytes were unaffected. TLR2 agonists doubled the T cell proliferation, likely of a selective population, given the net decrease of T cells. Subsequent chronic exposure experiments without GF, using PBMC and PBL cultures, showed a significantly (p &lt, 0.0001) increased proinflammatory cytokine production of TNF-&alpha, and IL-1&beta, up to 21 days only in TLR2-activated PBMC with concomitant T cell proliferation, suggesting a role for monocytes. In conclusion, chronic TLR activation mediates the shift in cell populations during infection. Particularly, TLR2 activators play an important role in T cell proliferation and proinflammatory cytokine production by monocytes, suggesting that TLR2 activation represents a bridge between innate and adaptive immunity.

Een 58-jarige man wordt door zijn tandarts verwezen naar de MKA-chirurg met de vraag of de restdentitie kan worden verwijderd en de reeds vervaardigde volledige immediaatgebitsprothese aansluitend kan worden geplaatst. Patiënt wil de behandeling vanwege extreme angst voor tandheelkundige behandelingen onder algehele narcose laten plaatsvinden. Ten tijde van het consult is hij klachtenvrij. Patiënt heeft een blanco medische voorgeschiedenis en gebruikt geen medicijnen. Bij intraoraal onderzoek wordt een gemutileerde restdentitie gezien met in de molaarstreek van de bovenkaak beiderzijds verdiepte pockets tot 8 mm. Er zijn geen afwijkingen van het mondslijmvlies. Op een vervaardigde panoramische röntgenopname wordt gegeneraliseerd horizontaal paradontaal botverlies gezien. Daarnaast valt een scherp begrensde lineaire radiopake structuur op aan de achter- en onderzijde van de mandibula die rechts meer uitgesproken is dan links (figuur 1).

Het syndroom van Sjörgren (SS) is een auto-immuunziekte waarbij de exocriene klieren zijn betrokken. Met name de traan-en speekselklieren zijn vaak aangedaan. een droge mond en ogen zijn hiervan het gevolg. Tevens zijn er vaak ook aspecifieke symptonen aanwezig, zoals algehele malaise en vermoeidheid. SS komt vooral voor bij vrouwen - met een vrouw-manration van 9:1 - en kan op elke leeftijd voorkomen. Tandartsen en mondhygiënisten spelen een zeer belangrijke rol in het zo gezond mogelijk houden van de mond en dentitie van deze patiënten. In dit artikel wordt besproken wat het syndroom van Sjörgren is. Ook besteden we aandacht aan hoe het kan worden vastgesteld of een mond droog is.

Human papillomavirus (HPV)-induced oropharyngeal squamous cell carcinoma (OPSCC) remains increasing worldwide. We aimed to investigate if the HPV-prevalence of OPSCC in the Netherlands is rising as well, also in female patients. In addition, we evaluated the association between HPV-positive OPSCC and suspicious Pap results of the cervix in these female patients. Patients with OPSCC treated in the period 2000–2015 at the VU University Medical Center Amsterdam, were included (n = 926). The presence of an oncogenic HPV infection was determined by p16-immunostaining, followed by a high-risk HPV general primer 5+/6+ DNA PCR on the p16-immunopositive cases. A review of pathology reports in all female patients (n = 305) was undertaken to identify cytological signs of HPV-related (pre)cancer of the cervix. In total 281 of 926 (30.3%) OPSCCs were HPV-positive. Moreover, a significant increase in the prevalence of HPV-positive OPSCCs was observed from 14.0% in 2000 to 48.1% in 2015 (p < 0.001). Among the female patients with an HPV-positive OPSSC (n = 70), the results of cervical smears were available in 56 of 70 patients (80.0%). Of the female patients with HPV-positive OPSCC, 9 of 56 (16.1%) patients had a vaginal cuff Papanicolaou (Pap) test ≥3b in their medical history compared to 7 of 168 (4.2%) in the HPV-negative group (p = 0.003). In conclusion, a continuous increase in the HPV-attributable fraction of OPSCC was demonstrated in the period 2000–2015 in the Amsterdam region. HPV-positive OPSCC has a significant association with a history of suspicious Pap results of the cervix in female patients.

Bij een patiënt met myasthenia gravis kan een levensbedreigendemyasthene crisis optreden. Het betreft een complicatie van deziekte. De crisis kan onder andere worden uitgelokt door emotionele stress,pijn, infecties en een reactie op medicatie. Het beleid bij een invasievetandheelkundige behandeling bij een patiënt met myasthenia gravis moetgericht zijn op het voorkomen van een crisis. Voorafgaand aan de behandelingis overleg met de behandelende neuroloog nodig omdat soms eerst optimalisatievan de medicatie of preventieve maatregelen noodzakelijk zijn. Eenbehandeling van een patiënt met myasthenia gravis onder lokale anesthesie vanhet amide-type of narcose is mogelijk, waarbij lokale anesthesie (in minimaledosering) de voorkeur heeft boven narcose. Na de tandheelkundige behandelingis optimaal pijnmanagement cruciaal om de kans op het optreden van een crisiste beperken.

ObjectivesTo assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren’s syndrome (SS).MethodsForty-nine patients with SS were randomly assigned to a control group (n=15) and two intervention groups: irrigation of the major glands with saline (n=16) or with saline followed by triamcinolone acetonide (TA) in saline (n=18). Unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) score and the European League Against Rheumatism (EULAR) SS Patient-Reported Index (ESSPRI) were obtained 1 week (T0) before, and 1 (T1), 8 (T8), 16 (T16) and 24 (T24) weeks after sialendoscopy.ResultsMedian baseline UWS, SWS and SPF scores were 0.14, 0.46 and 0.22 mL/min, respectively. After intervention, significant increases in UWS and SWS were observed in the saline group (at T8 (P=0.013) and T24 (P=0.004)) and the saline/TA group (at T24 (P=0.03) and T=16 (P=0.035)). SPF was increased significantly in the saline/TA group at T24 (P=0.03). XI scores declined after sialendoscopy in both intervention groups. Compared with the control group, CODS, XI and ESSPRI improved in the intervention groups. UWS, SWS and SPF were higher in the intervention groups compared with the control group, but these differences were not significant except for SPF in the saline/TA group at T24 (P=0.005).ConclusionsIrrigation of the major salivary glands in patients with SS enhances salivary flow and reduces xerostomia up to 6 months after sialendoscopy.

This study aimed to assess the value of cone beam computed tomography (CBCT) in the detection of salivary stones in patients with signs and symptoms of salivary gland obstruction. A total of 142 major salivary glands were analysed in a cohort of 127 patients with signs and symptoms of salivary gland obstruction. CBCT scans were performed in order to determine the presence of one or more salivary stones. All glands were also investigated by sialendoscopy. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for the submandibular gland, the parotid gland, and the whole group, based on the observers' abilities to diagnose the presence or absence of calculi in the CBCT scan using the sialendoscopy data as the gold standard. Fifty salivary stones were detected in the CBCT scans of the 142 glands analysed: 34 in the submandibular gland and 16 in the parotid gland. The sensitivity (94%), specificity (90%), positive predictive value (84%), and negative predictive value (97%) for the whole group were good to excellent, with an overall accuracy of 92%. CBCT appears to be an ideal first-line imaging modality for patients with signs and symptoms of obstructed major salivary glands.

The purpose of this study was to explore the association of the clinical oral dryness score (CODS) with salivary flow rates, xerostomia inventory (XI), and bother index (BI). 147 patients were screened using CODS, which determined 10 features of oral dryness. Each feature contributed 1 point, and the total score varied from 0 to 10. Unstimulated (UWS), chewing-stimulated (CH-SWS) and acid-stimulated (A-SWS) whole salivary flows and the XI and BI were measured. Associations were explored with a bootstrapped Spearman rank correlation test (1000 × bootstrapping). Based on unstimulated salivary flow, 55 patients were classified as hyposalivators, 31 as low salivators, 48 as normosalivators and 13 as high salivators. Median CODS in the hyposalivation group was 5 (IQR 3–6) compared with 3 (IQR 2–5) in the low salivation group, 2 (IQR 1–4) in the normal salivation group and 2 (IQR 1–2.5) in the high salivation group. Significant associations between CODS and the other parameters were only found in the hyposalivation group between CODS and UWS (ρ(53) = − 0.513; p

Objective: To assess the accuracy of five different computed tomography (CT) scanners for the evaluation of the oropharynx morphology. Methods: An existing cone-beam computed tomography (CBCT) data set was used to fabricate an anthropomorphic phantom of the upper airway volume that extended from the uvula to the epiglottis (oropharynx) with known dimensions (gold standard). This phantom was scanned using two multi-detector row computed tomography (MDCT) scanners (GE Discovery CT750 HD, Siemens Somatom Sensation) and three CBCT scanners (NewTom 5G, 3D Accuitomo 170, Vatech PaX Zenith 3D). All CT images were segmented by two observers and converted into standard tessellation language (STL) models. The volume and the cross-sectional area of the oropharynx were measured on the acquired STL models. Finally, all STL models were registered and compared with the gold standard. Results: The intra- and inter-observer reliability of the oropharynx segmentation was fair to excellent. The most accurate volume measurements were acquired using the Siemens MDCT (98.4%; 14.3 cm3) and Vatech CBCT (98.9%; 14.4 cm3) scanners. The GE MDCT, NewTom 5G CBCT, and Accuitomo CBCT scanners resulted in smaller volumes, viz., 92.1% (13.4 cm3), 91.5% (13.3 cm3), and 94.6% (13.8 cm3), respectively. The most accurate cross-sectional area measurements were acquired using the Siemens MDCT (94.6%; 282.4 mm2), Accuitomo CBCT (95.1%; 283.8 mm2), and Vatech CBCT (95.3%; 284.5 mm2) scanners.The GE MDCT and NewTom 5G CBCT scanners resulted in smaller areas, viz., 89.3% (266.5 mm2) and 89.8% (268.0 mm2), respectively. Limitations: Images of the phantom were acquired using the vendor-supplied default airway scanning protocol for each scanner. Conclusion: Significant differences were observed in the volume and cross-sectional area measurements of the oropharynx acquired using different MDCT and CBCT scanners.The Siemens MDCT and the Vatech CBCT scanners were more accurate than the GE MDCT, NewTom 5G, and Accuitomo CBCT scanners. In clinical settings, CBCT scanners offer an alternative to MDCT scanners in the assessment of the oropharynx morphology.

This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)

Background: There is a great interest in developing biomarkers to enhance early detection and clinical management of tongue squamous cell carcinoma (TSCC). However, the developmental path towards a clinically valid biomarker remains extremely challenging. Ideally, the initial key step in moving a newly discovered biomarker towards clinical implementation is independent replication. Therefore, the focus of this review is on biomarkers that consistently showed clinical relevance in two or more publications. Methods: We searched PubMed database for relevant papers across different TSCC sample sources, i.e., body fluids (saliva, serum/plasma) and tissues. No restriction regarding the date of publication was applied except for immunohistochemistry (IHC); only studies published between 2010 and June 2017 were included. Results: The search strategy identified 1429 abstracts, of which 96 papers, examining 150 biomarkers, were eventually included. Of these papers, 66% were exploratory studies evaluating single or a panel of biomarkers in one publication. Ultimately, based on studies that had undergone validation for their clinical relevance in at least two independent studies, we identified 10 promising candidates, consisting of different types of molecules (IL-6, IL-8, and Prolactin in liquid samples; HIF-1α, SOX2, E-cadherin, vimentin, MALAT1, TP53, and NOTCH1 in tissue biopsies).Conclusions: Although more exploratory research is needed with newer methods to identify biomarkers for TSCC, rigorous validation of biomarkers that have already shown unbiased assessment in at least two publications should be considered a high priority. Further research on these promising biomarkers or their combination in multi-institutional studies, could provide new possibilities to develop a specific panel for early diagnosis, prognosis, and individualized treatments.

Objective: The purpose of this contribution is to discuss how the subject of oral leukoplakia might be communicated among the various healthcare workers and also among patients. Material and Methods: The discussion is based on the available literature and on many decades of clinical and histopathological experience of the author. Results: The literature does not contain guidelines on what level of expertise can be expected from the various dental and medical healthcare workers in the field of oral leukoplakia, nor on how to communicate this disorder with patients. Based on personal experience, a number of suggestions have been proposed to overcome this shortcoming. Conclusion: Knowledge about oral leukoplakia varies among the various healthcare workers, depending on their level of expertise. Communication on this subject with patients should be in easy to understand wording, avoiding professional terminology as much as possible.

The aim of this study was to define the acid-etching technique for bone samples embedded in polymethyl metacrylate (PMMA) in order to visualize the osteocyte lacuno-canalicular network (LCN) for scanning electron microscopy (SEM). Human jaw bone tissue samples (N = 18) were collected from the study population consisting of patients having received dental implant surgery. After collection, the bone samples were fixed in 70% ethanol and non-decalcified samples embedded routinely into polymethyl metacrylate (PMMA). The PMMA embedded specimens were acid-etched in either 9 or 37% phosphoric acid (PA) and prepared for SEM for further analysis. PMMA embedded bone specimens acid-etched by 9% PA concentration accomplishes the most informative and favorable visualization of the LCN to be observed by SEM. Etching of PMMA embedded specimens is recommendable to start with 30 s or 40 s etching duration in order to find the proper etching duration for the samples examined. Visualizing osteocytes and LCN provides a tool to study bone structure that reflects changes in bone metabolism and diseases related to bone tissue. By proper etching protocol of non-decalcified and using scanning electron microscope it is possible to visualize the morphology of osteocytes and the network supporting vitality of bone tissue.

Background: Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally caused by smoking and excessive alcohol consumption. However, in the last decades high-risk human papillomavirus (HPV) infections play an increasingly important role in tumorigenesis. HPV-driven OPSCCs are known to have a more favorable prognosis, which has led to important and marked changes in the recently released TNM-8. In this 8th edition, OPSCCs are divided based on p16 immunostaining, with p16 overexpression as surrogate marker for the presence of HPV. The aims of this study are to evaluate TNM-8 on a Dutch consecutive cohort of patients with p16-positive OPSCC and to determine the relevance of additional HPV DNA testing.Patients and methods: All OPSCC patients without distant metastases at diagnosis and treated with curative intent at VU University Medical Center (2000-2015) and Erasmus Medical Center (2000-2006) were included (N = 1204). HPV status was determined by p16 immunostaining followed by HPV DNA PCR on the p16-immunopositive cases. We compared TNM-7 and TNM-8 using the Harrell's C index.Results: In total, 388 of 1204 (32.2%) patients were p16-immunopositive. In these patients, TNM-8 had a markedly better predictive prognostic power than TNM-7 (Harrell's C index 0.63 versus 0.53). Of the 388 p16-positive OPSCCs, 48 tumors (12.4%) were HPV DNA-negative. This subgroup had distinct demographic, clinical and morphologic characteristics and showed a significantly worse five-year overall survival compared with the HPV DNA-positive tumors (P Conclusions: TNM-8 has a better predictive prognostic power than TNM-7 in patients with p16-positive OPSCC. However, within p16-positive OPSCCs, there is an HPV DNA-negative subgroup with distinct features and a worse overall survival, indicating the importance to perform additional HPV DNA testing when predicting prognosis and particularly for selecting patients for de-intensified treatment regimens.

Objectives: The aberrant expression of mucins and mucin-type carbohydrates has been described in many types of cancer, including mucoepidermoid carcinoma (MEC), a malignant salivary gland tumor. In this study, we examined the aberrant expression patterns of mucins (MUC1, MUC4, MUC5AC and MUC5B), simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) and mature carbohydrate antigens (Lewisa and sulfo-Lewisa antigens) in MEC originating from the parotid gland, which normally does not secrete mucins. Design: We conducted an immunohistochemical study to investigate the presence of mucins and carbohydrates in 24 MEC samples originating from the parotid gland and in surrounding normal tissue of the same gland in comparison 6 samples of normal salivary glands. The expression levels were compared with respect to the histological grading. Furthermore, 24 MEC samples from non-parotid salivary glands were included. Results: We observed loss of topology of membrane-bound MUC1 and MUC4, and de novo expression of MUC5AC, MUC5B and sialyl-Tn in MEC that originated in the parotid gland. Furthermore, mucins MUC1, MUC4 and carbohydrate antigens Tn, sialyl-Tn, T, Lewisa and sulfo-Lewisa were overexpressed in MEC samples compared to surrounding normal salivary gland tissues. MUC1 was expressed in both low- and high grade MECs, whereas MUC4 was not expressed in high grade MECs of the parotid gland. Conclusion: During the development of MEC in the parotid gland, the genes for gel-forming secretory mucins are switched on. Besides these MEC tissues overexpress short oligosaccharides, suggesting that the glycosylation machinery is altered.

The biochemical composition of articaine differs from other amide anaesthetics. The lipophilic part of articaine consists of a thiophene ring, whereas other amide anaesthetics contain a benzene ring. When used correctly, local anaesthetics are remarkably safe. However, all local anaesthetics are potentially neurotoxic. In rare cases a prolonged abnormal perception/sensation may be present after the expected duration of action (paraesthesia). In several countries retrospective studies have been conducted that examined the incidence of persistent paraesthesia after the use of local anaesthetics. In most studies the number of paraesthesia cases after the use of articaine was higher than the market share of this anaesthetic. In animal studies and in cell culture experiments, however, articaine did not have a higher toxicity compared to other amide anaesthetics. Further studies of the cause of paraesthesia after administration of local anaesthetics seem to be warranted.

Purpose: To assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1–T2) oral cancer and a clinically negative neck (cN0). Methods: In addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator. Results: Identification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort. Conclusions: The addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

Purpose: Recent literature suggests that sialendoscopy of the major salivary glands could alleviate symptoms of Sjögren syndrome (SS) and restore salivary function. The aim of this study was to evaluate the authors’ experience of sialendoscopy of the salivary glands in patients with SS. Materials and Methods: In this retrospective case series study, the surgical data of patients with SS who had undergone sialendoscopy at the VU University Medical Center (Amsterdam, The Netherlands) from November 2014 through April 2015 were used. Outcome measurements were successful entry to the salivary gland and completion of sialendoscopy as planned. Furthermore, pre- and postoperative complications were scored. Descriptive analysis of the data was performed. Results: Surgical data of sialoendoscopic procedures in 26 patients with SS (24 women and 2 men; mean age, 57 yr; range, 27 to 72 yr) were analyzed. Sialendoscopy was successfully performed in 78 of 104 salivary glands (75%; 50 parotid and 28 submandibular glands) in the 26 patients. Sialendoscopy failed in 26 of the 104 sialoendoscopic procedures (25%; 2 parotid and 24 submandibular glands). In 16 salivary glands, the ductal orifice could not be identified. In 7 salivary glands, sialendoscopy could not be performed because of partial or complete stenosis of the salivary duct. In 3 salivary glands, sialendoscopy was not performed because of a ductal perforation. Three patients developed a postoperative infection. Conclusion: The overall rate of complications was limited and the sialoendoscopic complications in patients with SS could be regarded as minor. Most complications were seen for sialendoscopy of the submandibular glands in this specific patient category. Careful preoperative selection of patients and salivary glands could contribute to a lower rate of complications and more predictable results.

Ulcerative colitis is a rather common inflammatory bowel disease, especially in the industrialised world. A limited number of studies have reported the prevalence of oral signs and symptoms in these patients, and widely varying prevalence rates have been reported ranging from 2 to 34%. Pyostomatitis vegetans is the most pathognomonic oral sign but also other abnormalities as oral ulcerations, caries and periodontitis are more often seen in patients with ulcerative colitis. In this review we describe the oral manifestations of ulcerative colitis and their potential dental implications.

Contains fulltext : 171056.pdf (Publisher’s version ) (Open Access) BACKGROUND: Data on non-small-cell lung cancer (NSCLC) patients with non-classic epidermal growth factor receptor (EGFR) mutations are scarce, especially in non-Asian populations. The purpose of this study was to evaluate prevalence, clinical characteristics and outcome on EGFR-TKI treatment according to type of EGFR mutation in a Dutch cohort of NSCLC patients. METHODS: We retrospectively evaluated a cohort of 240 EGFR-mutated NSCLC patients. Data on demographics, clinical and tumour-related features, EGFR-TKI treatment and clinical outcome were collected and compared between patients with classic EGFR mutations, EGFR exon 20 insertions and other uncommon EGFR mutations. RESULTS: Classic EGFR mutations were detected in 186 patients (77.5%) and non-classic EGFR mutations in 54 patients (22.5%); 23 patients with an exon 20 insertion (9.6%) and 31 patients with an uncommon EGFR mutation (12.9%). Median progression-free survival (PFS) and overall survival (OS) on EGFR-TKI treatment were 2.9 and 9.7 months, respectively, for patients with an EGFR exon 20 insertion, and 6.4 and 20.2 months, respectively, for patients with an uncommon EGFR mutation. Patients with a double uncommon EGFR mutation that included G719X/L861Q/S768I had longer PFS and OS on EGFR-TKI treatment compared with patients with a single G719X/L861Q/S768I EGFR mutation (both P=0.02). CONCLUSIONS: In our Dutch cohort, prevalence and genotype distribution of non-classic EGFR mutations were in accordance with previously reported data. The PFS and OS on EGFR-TKI treatment in patients with an uncommon EGFR mutation were shorter compared with patients with classic EGFR mutations, but varied among different uncommon EGFR mutations. 9 p.

Tandartsen worden met enige regelmaat geconfronteerd met pigmentaties van het mondslijmvlies en het tandvlees. De oorzaken kunnen velerlei zijn. Wanneer is waakzaamheid geboden? Deze bijdrage beoogt de tandarts houvast te geven voor het stellen van de diagnose en advies te geven voor het verdere beleid.

Orale leukoplakie is een premaligne, overwegend witte laesie van het mondslijmvlies, die bij ongeveer 0,1% van de bevolking voorkomt. Meestal betreft het patiënten boven het 30e levensjaar; de laesie komt ongeveer even vaak bij mannen als bij vrouwen voor. In het merendeel van de gevallen betreft het rokers. Leukoplakie kan overal in het mond- en tongslijmvlies en ook op de gingiva voorkomen en gaat soms gepaard met klachten van een ruw en soms geirriteerd gevoel. De kans op het ontstaan van mondkanker vanuit leukoplakie bedraagt 2%-3% per jaar. Er zijn geen betrouwbare factoren voorhanden die bij een individuele patiënt toekomstige kwaadaardigheid kunnen voorspellen. Wel is de kans daarop vooral vergroot bij lokalisatie op de tongranden of de mondbodem. Dat geldt ook voor de grootte van de leukoplakie: hoe groter des te meer kans op kwaadaardige verandering. Wat moet een tandarts ermee?

Kwaadaardige processen komen relatief zelden in het bovenkaakbot of de kaakholte, de sinus maxillaris, voor. Het gaat daarbij om verschillende vormen van kwaadaardigheid, variërend van kanker in het bekledende slijmvlies van de sinus maxillaris, tot speekselklierkanker, botkanker, kanker van lymfoïd weefsel en een enkele maal zelfs een uitzaaiing van een elders in het lichaam gelegen kwaadaardig proces.De klinische en röntgenologische veranderingen kunnen zeer uiteenlopend zijn. Bij de meeste van de hier genoemde tumorsoorten betreft het oudere patiënten. Een uitzondering is het sarcoom van het kaakbot, waarbij kan het ook om jeugdige patiënten gaan.De klachten van met name bijholtekanker kunnen bestaan uit neusverstopping, hoogstand van één van de ogen, spontane neusbloedingen en soms uitval van de n. infraorbitalis. Soms gaat het om dentogeenachtige klachten, bestaande uit onverklaarbare kiespijn en mobiele gebitselementen.In de hierna te bespreken patiëntengeschiedenissen zal vooral worden stilgestaan bij de rol van de tandarts bij de diagnostiek.

Objective: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. Materials and methods: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. Results: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p

Objective: The aim of this study was to analyze the complications and outcomes of surgical treatment of angle fractures managed at departments of maxillofacial surgery in several European countries. Study Design: Patients hospitalized with unilateral isolated angle fractures between 2013 and 2017 were included. The following data were recorded: gender and age of patients, fracture etiology, presence of the third molar, maxillomandibular fixation, osteosynthesis technique, and complications. Results: In total, 489 patients were included in the study. The Champy technique was found to be the most frequently chosen osteosynthesis technique. Sixty complications were observed, at a rate of 12.3%. Complications were associated with the absence of third molars (P < .05). Instead, the Champy technique was associated with fewer complications (P < .05), in comparison with the other adopted techniques. Conclusions: The management of angle fractures still represents a challenging task with a significant complication rate. The Champy technique still seems to be a valid option for the treatment of such injuries.

Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by heterotopic ossification (HO). The disease is caused by a mutation in the activin receptor type 1 (ACVR1) gene that enhances this receptor's responsiveness to Activin‐A. Binding of Activin‐A to the mutated ACVR1 receptor induces osteogenic differentiation. Whether Activin‐A also affects osteoclast formation in FOP is not known. Therefore we investigated its effect on the osteoclastogenesis‐inducing potential of periodontal ligament fibroblasts (PLF) from teeth of healthy controls and patients with FOP. We used western blot analysis of phosphorylated SMAD3 (pSMAD3) and quantitative polymerase chain reaction to assess the effect of Activin‐A on the PLF. PLF‐induced osteoclast formation and gene expression were studied by coculturing control and FOP PLF with CD14‐positive osteoclast precursor cells from healthy donors. Osteoclast formation was also assessed in control CD14 cultures stimulated by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of nuclear factor kappa‐B ligand (RANK‐L). Although Activin‐A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID‐1) expression only in FOP PLF. Activin‐A inhibited PLF mediated osteoclast formation albeit only significantly when induced by FOP PLF. In these cocultures, it reduced M‐CSF and dendritic cell‐specific transmembrane protein (DC‐STAMP) expression. Activin‐A also inhibited osteoclast formation in M‐CSF and RANK‐L mediated monocultures of CD14+ cells by inhibiting their proliferation. This study brings new insight on the role of Activin A in osteoclast formation, which may further add to understanding FOP pathophysiology; in addition to the known Activin‐A‐mediated HO, this study shows that Activin‐A may also inhibit osteoclast formation, thereby further promoting HO formation.

Purpose: To evaluate possible risk factors associated with wound dehiscences following pre-implant alveolar bone augmentation with autologous anterior iliac crest bone grafts covered with resorbable collagen membranes or human demineralised bone laminae. Materials and methods: Data of 161 patients who underwent bone augmentation prior to the insertion of dental implants were analysed. The preoperative dental status, locations of alveolar bone augmentation sites and location of wound dehiscences were recorded. Gender, age, smoking, alcohol exposure, and dental and medical histories were reviewed. Information was also collected on the surgeons, augmentation technique, application of a collagen membrane, fixation screw type and suture material. Univariate logistic regression analysis was used to evaluate pre- and perioperative variables as predictors of dehiscences. Results: A total of 42 (26.1%) of the 161 augmented patients developed a wound dehiscence following surgery. Most commonly affected sites were the anterior maxilla, followed by the anterior mandible. Males developed wound dehiscences with higher probability than females (odds ratio female = 0.444; P = 0.025; 95% CI: 0.214 to 0.903). Furthermore, marginal associations (P < 0.10) are found for smoking and an anterior location of the augmentation. Smokers were found to have higher probability of a wound dehiscence (odds ratio 2.089; P = 0.064; 95% CI: 0.957 to 4.500) compared to non-smokers. A posterior location of the augmentation was associated with lower probability of a wound dehiscence (odds ratio 0.188; P = 0.076; 95% CI: 0.035 to 0.802) compared to an anterior location. Conclusions: Based on this study population, smoking in males seems to be the most important risk factor for the development of wound dehiscences after pre-implant alveolar bone augmentation procedures.

Purpose: Fractures of the zygomaticomaxillary complex (ZMC) are common injuries that may lead to loss of an aesthetically pleasing appearance and functional impairment. The aim of this study was to analyze the demographics, causes, characteristics, and outcomes of zygomatic fractures managed at several European departments of oral and maxillofacial surgery. Materials and methods: This study is based on a multicenter systematic database that allowed the recording of all patients with ZMC fractures between 1 January 2013 and 31 December 2017. The following data were recorded: gender, age, personal medical history, etiology, side of zygomatic fracture, classification of ZMC fracture, associated maxillofacial fractures, symptoms at diagnosis, type of performed treatment, and sequelae/complications. Results: A total of 1406 patients (1172 males, 234 females) were included in the study. Statistically significant correlations were found between assault-related ZMC fractures and the A3 class (p

In deze rubriek zullen röntgenopnamen worden getoond zoals u ze dagelijks in de praktijk kunt tegenkomen. Elke röntgenfoto kan echter iets verrassends laten zien, ook al is de reden om de opname te maken heel gewoon. Elke opname dient daarom beoordeeld te worden zonder beïnvloeding van vooraf gestelde verwachtingen. De röntgenopnamen die in deze rubriek worden opgenomen bevatten een diagnostisch probleem. Soms zult u het gemakkelijk herkennen, soms wellicht ook niet direct.

In deze rubriek zullen röntgenopnamen worden getoond zoals u ze dagelijks in de praktijk kunt tegenkomen. Elke röntgenfoto kan echter iets verrassends laten zien, ook al is de reden om de opname te maken heel gewoon. Elke opname dient daarom beoordeeld te worden zonder beïnvloeding van vooraf gestelde verwachtingen. De röntgenopnamen die in deze rubriek worden opgenomen bevatten een diagnostisch probleem. Soms zult u het gemakkelijk herkennen, soms wellicht ook niet direct.

Purpose: The aim of this study was to analyze the demographic variables and causes and characteristics of mandibular angle fractures managed at several European departments of maxillofacial surgery. Materials and Methods: This study was based on a multicenter systematic database that allowed the recording of data from all patients with mandibular angle fractures between January 1, 2013, and December 31, 2017. The following data were recorded: gender, age, etiology, side of angle fracture, associated mandibular fractures, presence of third molar, intermaxillary fixation, and osteosynthesis. Results: The study included 1,162 patients (1,045 male and 117 female patients). A significant association was found between the presence of a third molar and the diagnosis of an isolated angle fracture (P

Comparing accuracy results for mandibular reconstructions using computer-assisted surgery (CAS) is limited due to heterogeneity in image acquisition, extent of mandibular resection, and evaluation methodologies between studies. We propose a practical, feasible and reproducible guideline for standardizing evaluation methods to allow valid comparisons of postoperative results and facilitate meta-analyses in the future. It offers a guide to imaging, data comparison, volume assessment of 3-dimensional models, classification of defects, and it also contains a quantitative accuracy evaluation method.

The aim of this study is to assess dental students’ opinions of the dentists’ role in primary prevention of human papillomavirus (HPV)-related oral cancer using a cross-sectional web-based survey. A questionnaire, containing questions about knowledge of HPV and oral cancer, confidence in head and neck examination and role of the dentist in preventing HPV-related oral cancer, was sent to all students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and twenty-six (n = 126) students completed the questionnaire. Significantly, more master students (75%) than bachelor students (54.3%) were aware that HPV is a causative factor for oral cancer. Master students had more knowledge of HPV than bachelor students, but knowledge about HPV vaccination was irrespective of the study phase. The majority of dental students agreed that it is important to discuss HPV vaccination with patients. Eighty-nine percent of the students think that more education about symptoms of oral cancer will increase screening for oral cancer. Development of a protocol for screening in dental practices was considered even more important. According to dental students, dentists should discuss HPV as a risk factor for oral cancer with patients. Future dentists are willing to be involved in both primary and secondary prevention of HPV-related oral cancer. Therefore, screening for oral cancer and education about HPV vaccination should be integral elements of the dental curriculum.

Objectives: Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow. Materials and methods: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point 2). Results: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels. Conclusions: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored.

Background: We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease. Methods: A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured. Distant disease-free survival (DDFS) and time to death since distant metastases diagnosis were analyzed. Results: Forty-two percent of the patients were diagnosed with distant metastases. DDFS showed significant negative associations with advanced T classification, N+ classification, solid type tumor, and positive surgical margins. Distant metastases (91%) developed in the first 5 years after presentation. Median distant metastatic survival was 13.8 months. The most frequent organ sited was the lung. Solid type ACC showed a preponderance for multiorgan metastases (17/28; 61%). Distant metastases seemed not to occur in case of clear surgical margins. Solid type ACC had a significant poorer survival after development of distant metastases. Conclusion: Metastatic ACC is not always an indolent disease.

Background. We retrospectively analyzed the incidence and types of postoperative complications after mandibular continuity reconstructions with fibular free flaps (FFF) in patients with oral squamous cell carcinoma (OSCC) and identified potential risk factors for postoperative complications.Methods. Data were retrieved from the medical records in the Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands from April 1995 to September 2013, and were statistically analyzed.Results. In this study, 85 patients were included in whom 86 FFFs were used for mandibular reconstruction. Thirty-seven patients (43%) developed ≥ 1 surgical complication and 9 patients (10.5%) developed ≥ 1 systemic complication. Three patients (3.5%) developed total flap failure and six patients (7.0%) developed partial flap failure. Surgical complications were correlated with tobacco use, partial glossectomy, type of mandibular defect, and anatomic staging. Systemic complications were associated with age > 60 years and Charlson comorbidity index > 2. Hospitalization > 30 days was associated with type of mandibular defect.Conclusions. The use of the FFF for reconstructing mandibular continuity defects in OSCC patients may be associated with postoperative complications. Patients with coexisting medical conditions and anterior mandibular defects have an increased risk for developing complications. Patients who undergo segmental mandibular resection including a partial glossectomy could have a reduced risk for complications.

Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17+ non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p

Een klinisch patholoog is een medisch specialist, die door weefsel- en celonderzoek te doen een diagnose stelt. Met kennis van de bouw van normaal weefsel, kan de patholoog afwijkingen, zoals kanker of een ontsteking, herkennen. Kanker wordt vrijwel altijd vastgesteld door microscopisch onderzoek door de patholoog.

Op tandheelkundige röntgenfoto’s worden soms onverwachte afwijkingen gezien die geen klachten veroorzaken en derhalve eigenlijk als toevalsbevinding moeten worden aangemerkt. Als het om een afwijkend beeld in de directe omgeving van de gebitselementen gaat, zullen tandartsen vermoedelijk meestal wel weten wat er aan de hand is. Mocht dat onverhoopt niet het geval zijn, ligt overleg met een meer deskundige voor de hand; vaak zal dat een MKA-chirurg zijn. Bij het toevalligerwijs aantreffen van een afwijking buiten het directe werkterrein van de tandarts, rijzen er toch wel wat vragen. Ligt het wel op de weg van de tandarts er nader aandacht aan te besteden? Moet de patiënt wel worden geïnformeerd en zorgt dat niet voor onnodige onrust? En, als er toch advies van een meer deskundige wenselijk is, wie moet dat dan zijn? Laten we maar eens een aantal casussen bespreken.

Background To analyze the prevalence and location of tooth loss in Sjögren’s syndrome (SS) patients and compare them with an age- and gender-matched control group. Material and Methods Dental charts and x-rays of 108 (SS) patients were retrieved from an academic dental center and special care dentistry department. For each SS patient, an age- and gender-matched non-SS patient was randomly selected. Medication, number of extractions and date and location of extractions were assessed. Differences between SS and non-SS patients were analyzed using Mann-Whitney U tests, Chi-square tests and Fisher’s exact tests. Results Significantly more SS patients were edentulous compared to the non-SS group (14.8% versus 1.9%, p = 0.001). SS patients had a 61% higher risk to have experienced one or more extractions than control patients. In the SS group, there was a non-significant tendency for more maxillary teeth to have been extracted than mandibular teeth (42:34). In the control group, the number of extractions in the maxilla and mandible were comparable (21:20). When divided into sextants, the number of SS patients with one or more extractions was significantly higher than for non-SS patients for each sextant (p = 0.001 to p = 0.032). The largest difference in the proportion of patients with one or more extractions between the SS and non-SS patients occurred in the upper anterior sextant (3.4 times more frequent). Conclusions SS patients are more prone to experience dental extractions compared to patients without SS. It could be speculated that this is related to a decreased salivary secretion. Key words:Sjögren’s syndrome, dentition, edentulism, extractions, dental health.

Background Salivary stones are calcified structures most often found in the main duct of the submandibular or parotid salivary gland. They contain of a core surrounded by laminated layers of organic and inorganic material. Material and Methods Submandibular and parotid sialoliths (n=155) were collected at the department of Oral and Maxillofacial surgery of a general hospital between February 1982 and September 2012. The weight of the sialoliths was determined and the consistency was subjectively classified. Subsequently, the biochemical composition of the stones was determined by wet chemical methods or FT-IR spectrometry. Age and gender of the patients were retrieved from their medical records. Data were statistically analyzed using Fisher’s exact tests. Results Sialoliths are mainly composed of inorganic material. Carbonate apatite was identified in 99% of the stones, phosphate in 88%, calcium in 87%, magnesium in 68%, struvite in 44%, oxalate in 38% and carbonate in 35%. Solid salivary stones contain more frequently struvite than stones with a soft consistency (p=0.05). Larger stones (>100mg) contain more frequently carbonate (p=0.05). Stones from older patients (≥38years) showed an almost significant trend towards more frequent presence of phosphate (p=0.083). Conclusions The biochemical composition of submandibular and parotid sialoliths is related to stone-related factors, probably to age but not to the gender of the patient. Key words:Salivary stone, sialolith, biochemical composition, FT-IR spectrometry.

In deze rubriek zullen röntgenopnamen worden getoond zoals u ze dagelijks in de praktijk kunt tegenkomen. Elke röntgenfoto kan echter iets verrassends laten zien, ook al is de reden om de opname te maken heel gewoon. Elke opname dient daarom beoordeeld te worden zonder beïnvloeding van vooraf gestelde verwachtingen. De röntgenopnamen die in deze rubriek worden opgenomen bevatten een diagnostisch probleem. Soms zult u het gemakkelijk herkennen, soms wellicht ook niet direct.