Letter to the Editor, "Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis".

This article is temporarily under embargo.

[A PhD completed. General conclusions of doctoral research into regional mouth dryness]. / Serie: Hora est. Algemene conclusies promotieonderzoek naar regionale monddroogte.

Dry mouth has a complex aetiology which makes proper diagnosis complicated. Until now, dry mouth diagnosis has mainly focused on the overall oral dryness, without taking into account regional differences within the mouth. This research showed, among other things, that there are unique patterns of oral dryness, each with its own cause. For example, patients suffering from Sjogren's syndrome mainly experienced dryness of the posterior of the palate. Patients with dry mouth due to the side effects of medication, in contrast, experienced the front part of the tongue as the driest. These findings suggest that mapping of intraoral dryness may be a useful diagnostic tool to differentiate between possible causes of dry mouth.

[Knowledge and attitude of oral care providers in the Netherlands on skin lesions]. / Kennis en attitude van mondzorgverleners over huidafwijkingen.

To gain insight into the current knowledge of oral care providers in the Netherlands on facial skin lesions, a survey was distributed to 7,670 oral care providers. Their knowledge was tested by means of 4 multiple-choice questions and on the basis of 5 cases. The survey was completed in full by 90 respondents. The median age was 50.3 years and 62.2% were female. During dental check-ups, 55.6% always examined the face and 41.1% sometimes did so. Compared to the group 41 years old and older, the group 21-40 years of age alerted their patients more often to skin lesions (p = 0.017), was more afraid a specialist would find the referral useless (p < 0.001) and was more in need of a guideline (p = 0.049). The respondents scored 1.90 out of 4 correct answers to the knowledge questions. On the case studies, they scored 1.46 out of 5 for the correct diagnosis, 3.48 out of 5 for the correct choice of policy and 1.01 out of 5 for the combination correct diagnosis and correct policy. The total score was 2.91 out of 9. The results indicate that knowledge on aspects of skin lesions is limited and additional training and the availability of a guideline are necessary.

Knowledge of diagnosis and management of selected oral mucosal lesions among dentists in The Netherlands.

BACKGROUND: Knowledge of oral mucosal lesions (OMLs) among dentists is relevant in diagnosing potentially malignant diseases and oral cancer at an early stage. The aim of this survey was to explore dentists' knowledge about OMLs. MATERIAL AND METHODS: Respondents to a web-based questionnaire, containing 11 clinical vignettes representing patients with various OMLs, provided a (differential) diagnosis and management for each. Information about demographics and clinical experience of the participants was acquired as well. Descriptive statistics were performed and T-tests were used to test for significant (p<0.05) differences in mean scores for correct diagnosis and management between subgroups based on demographic variables. RESULTS: Forty-four of 500 invited dentists completed the questionnaire. For (potentially) malignant OMLs, the number of correct diagnoses ranged from 14 to 93%, whilst the number of correct management decisions ranged from 43 to 86%. For benign OMLs, the number of correct diagnoses and management decisions ranged from 32 to 100% and 9 to 48%, respectively. For 11 clinical vignettes, mean scores for correct diagnosis, correct management and correct diagnosis and management were respectively 7.2 (±1.8), 5.7 (±1.5), and 3.8 (±1.7). CONCLUSIONS: The results show that dentists in the Netherlands do not have sufficient knowledge to accurately diagnose some OMLs and to select a correct management. This may result in over-referral of benign OMLs and under-referral for (potentially) malignant OMLs. Clinical guidelines, that include standardized criteria for referral, and continuing education, may improve dentists' ability to correctly diagnose and accurately manage OMLs.

Salivary film thickness and MUC5B levels at various intra-oral surfaces.

OBJECTIVES: In this study, we investigated the salivary film thickness and the MUC5B levels at various intra-oral locations in healthy volunteers, with a focus on the palate. Besides, measurements of the palatal surface area were included to explore the possible relationships between the palatal surface area and the palatal salivary film and MUC5B levels. MATERIALS AND METHODS: The salivary film thickness was determined using filter strips, which were pressed to the mucosal surfaces of five different intra-oral locations; conductance was then analysed using a Periotron. After elution of the strips, the MUC5B levels at various intra-oral locations were determined using ELISA. The palatal surface area was measured using an intra-oral scanner. The surface area was subsequently calculated using the software. RESULTS: The anterior tongue had the thickest salivary film and also the highest levels of MUC5B, while the anterior palate had the thinnest salivary film and lowest MUC5B levels. There was no association between the palatal surface area and the salivary film thickness of the palate. CONCLUSION: The salivary film and MUC5B levels are unequally distributed over the intra-oral regions of the soft tissues. The lack of association between the palatal surface area and the salivary film thickness indicates that a larger surface area is not associated with a relative thinner palatal salivary film. CLINICAL RELEVANCE: The results of the current study increase our understanding of saliva distribution in the oral cavity and could be used as reference values for future studies.

COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy.

BACKGROUND: COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. PATIENTS AND METHODS: At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. RESULTS: In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. CONCLUSIONS: While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.

Correlations of palatal surface area with anthropometric dimensions of the head and face.

PURPOSE: Saliva distribution over the palatal surface plays an important role in the perception of dry mouth. It is envisaged that non-invasive estimation of the palatal surface area by anthropometric measurements of the head and face can be useful in the assessment of oral dryness. For this purpose, the relationship between the palatal surface area and anthropometric measurements of the head and face was investigated. METHODS: The palatal surface was measured in 51 healthy volunteers using an intra-oral scanner. The distances between anthropometric landmarks of the head and face were determined using an anatomical sliding caliper. Correlations between the palatal surface area and the anthropometric landmarks were investigated. RESULTS: The median palatal surface area for the total study population was found to be 2120.6 mm2. Virtually, all anthropometric measurements showed significant differences between females and males. Various head and face measurements had a significant correlation with the palatal surface area. However, these correlations disappeared when the participants were stratified based on their sex, with the exception of mandibular length and palatal width in females. CONCLUSION: The surface area of the palate correlates with nearly all anthropometric measurements of the head and face included in this study. Yet, the clinical applicability seems limited to females.

[Human papillomavirus vaccination available for boys also; information for oral healthcare providers]. / Humaan papillomavirus-vaccinatie nu ook beschikbaar voor jongens: informatie voor mondzorgverleners.

Recently, the Dutch National Immunization Programme has started to offer the human papillomavirus (HPV) vaccination to boys as well as girls from the age of 10. The vaccine protects against long-term HPV infection, which can lead to cervical, anogenital and oropharyngeal cancer. Besides malignant disorders, a HPV infection can also lead to certain disorders of the skin and oral cavity. Since the national HPV vaccination campaign has probably resulted in more awareness among patients about the relation between HPV and oropharyngeal cancer, patients may consult oral healthcare professionals with questions about HPV infection. Oral healthcare professionals are thus able to play a role in preventing HPV related disorders by counseling their patients on HPV. They can also contribute to early diagnosis of HPV related oral and oropharyngeal disorder, although the possibility of detecting oropharyngeal cancer during routine dental examination  is limited.

FAP imaging in rare cancer entities-first clinical experience in a broad spectrum of malignancies.

PURPOSE: 68 Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors. MATERIAL AND METHODS: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a 68 Ga-FAPI-PET/CT scan. Fourteen women and 41 men (median age 60) were included within the following subgroups: cancer of unknown primary (n = 10), head and neck cancer (n = 13), gastrointestinal and biliary-pancreatic cancer (n = 17), urinary tract cancer (n = 4), neuroendocrine cancer (n = 4), and others (n = 7). Tracer uptake was quantified by standardized uptake values SUVmax and SUVmean and the tumor-to-background ratio (TBR) was determined (SUVmax tumor/SUVmean organ). RESULTS: In 20 out of 55 patients, the primary tumor was identified and 31 patients presented metastases (n = 88), characterized by a high mean SUVmax in primary (10.1) and metastatic lesions (7.6). The highest uptake was observed in liver metastases (n = 6) with a mean SUVmax of 9.8 and a high TBR of 8.7, closely followed by peritoneal carcinomatosis (n = 16) presenting a mean SUVmax of 9.8 and an excellent TBR of 29.6. In terms of the included subgroups, the highest uptake regarding mean SUVmax was determined in gastrointestinal and biliary-pancreatic cancer with 9.8 followed closely by urinary tract cancer with 9.5 and head and neck cancer (9.1). CONCLUSION: Due to excellent tumor visualization and, thereby, sharp contrasts in terms of high TBRs in primary and metastatic lesions in different rare malignancies, 68 Ga-FAPI-PET/CT crystallizes as a powerful and valuable imaging tool, particularly with respect to epithelial carcinomas, and therefore an enhancement to standard diagnostics imaging methodologies. The realization of further and prospective studies is of large importance to confirm the potential of FAP imaging in oncology.

[Knowledge of Dutch dentists regarding HPV associated cancer of the oropharynx]. / Kennis van Nederlandse tandartsen over orofarynxkanker veroorzaakt door het humaan papillomavirus.

Worldwide and also in the Netherlands there is an increasing human papillomavirus (HPV)-attributable oropharyngeal cancer incidence. This type of cancer is more common at a younger age than the classical oropharyngeal cancer, which is usually caused by smoking and excessive drinking. Most often, the tumor occurs in the tonsils and at the base of the tongue. This study explored the level of knowledge of dentists about oropharyngeal cancer, its association with the human papillomavirus and their willingness to play a role in prevention. 7.364 digital questionnaires were sent to oral health-care providers and data from 607 dentists was analyzed. 48% of knowledge questions were answered correctly by more than half of the respondents. Significantly more female caregivers were aware of the relationship between HPV and oropharyngeal cancer and the availability of an HPV vaccine. Respondents considered it important that the relationship between HPV and oropharyngeal cancer is discussed with patients and that a protocol is developed that is useful in screening for mouth and throat cancer.

Rationale and design of the CRAFT (Continuous ReAssessment with Flexible ExTension in Rare Malignancies) multicenter phase II trial.

BACKGROUND: Approvals of cancer therapeutics are primarily disease entity specific. Current molecular diagnostic approaches frequently identify actionable alterations in rare cancers or rare subtypes of common cancers for which the corresponding treatments are not approved and unavailable within clinical trials due to entity-related eligibility criteria. Access may be negotiated with health insurances. However, approval rates vary, and critical information required for a scientific evaluation of treatment-associated risks and benefits is not systematically collected. Thus clinical trials with optimized patient selection and comprehensive molecular characterization are essential for translating experimental treatments into standard care. PATIENTS AND METHODS: Continuous ReAssessment with Flexible ExTension in Rare Malignancies (CRAFT) is an open-label phase II trial for adults with pretreated, locally advanced, or metastatic solid tumors. Based on the evaluation by a molecular tumor board, patients are assigned to combinations of six molecularly targeted agents and a programmed death-ligand 1 (PD-L1) antagonist within seven study arms focusing on (i) BRAF V600 mutations; (ii) ERBB2 amplification and/or overexpression, activating ERBB2 mutations; (iii) ALK rearrangements, activating ALK mutations; (iv and v) activating PIK3CA and AKT mutations, other aberrations predicting increased PI3K-AKT pathway activity; (vi) aberrations predicting increased RAF-MEK-ERK pathway activity; (vii) high tumor mutational burden and other alterations predicting sensitivity to PD-L1 inhibition. The primary endpoint is the disease control rate (DCR) at week 16; secondary and exploratory endpoints include the progression-free survival ratio, overall survival, and patient-reported outcomes. Using Simon's optimal two-stage design, 14 patients are accrued for each study arm. If three or fewer patients achieve disease control, the study arm is stopped. Otherwise, 11 additional patients are accrued. If the DCR exceeds 7 of 25 patients, the null hypothesis is rejected for the respective study arm. CONCLUSIONS: CRAFT was activated in October 2021 and will recruit at 10 centers in Germany. TRIAL REGISTRATION NUMBERS: EudraCT: 2019-003192-18; ClinicalTrials.gov: NCT04551521.

The MemoFlex II, a non-robotic approach to follow-the-leader motion of a snake-like instrument for surgery using four predetermined physical tracks.

The fields of Minimally Invasive Surgery (MIS) and Natural Orifices Transluminal Endoscopic Surgery (NOTES) strive to reduce the level of invasiveness by entering the body through smaller incisions and natural orifices. Hyper-redundant snake-like instruments can help in this pursuit of reducing invasiveness. Such instruments can pass along multi-curved pathways through the body without any support or guidance from its anatomical environment. In this way, the width of the surgical pathway and thus the invasiveness of the procedure can be reduced significantly. This is referred to as Follow-the-Leader (FTL) motion. Generally, surgical instruments intended for FTL-motion are robotic systems that require medical grade actuators, sensors, and controllers, driving up costs and increasing their footprint in the operation room. Our goal was to discard the need for these elements and develop a non-robotic instrument capable of FTL-motion along pre-determined paths. A proof of concept prototype called MemoFlex II was developed, consisting of a cable-driven hyper-redundant shaft that is controlled via four physical tracks. The MemoFlex II was able to perform 3D FTL-motion along pre-determined paths. Among other things, this study reports on a Ø8 mm shaft containing seven segments and 14 degrees of freedom (DOFs) following several multi-curved paths with an average maximal footprint between 11.0 and 17.1 mm.

[Dry mouth. Case histories from a saliva clinic]. / De droge mond. Casuïstiek uit het speekselspreekuur.

Three patients who were referred to the saliva of the Center for Special Care Dentistry (Stichting Bijzondere Tandheelkunde, SBT) in Amsterdam clearly demonstrate that in the case of patients suffering from xerostomia, it can be useful to have the saliva secretion rate determined and to take saliva into account in the aetiology and in developing a dental treatment plan. In the first case, a 39-year-old woman presented with dry mouth associated with Sjögren's syndrome. A fair degree of saliva secretion was still possible. The teeth were characterised by wear, caries lesions and sensitivity. The second patient was a 42-year-old man suffering from dry mouth associated with the use of medications. His teeth were weakened to the point of deciding to create conventional full dentures, despite a possible moderate prognosis due to oral dryness. The third patient, a 79-year-old woman, was suffering from severe dry mouth, associated with Sjögren's syndrome. Due to the ruinous condition of her teeth and extreme dry mouth, the decision was made to remove the remaining dentition and insert implant-retained dentures.

[Saliva testing in the daily practice]. / Speekselonderzoek in de dagelijkse praktijk.

Saliva is a very multifaceted fluid with many different functions and it plays an essential role in oral health. With an aging population, dental professionals will increasingly be confronted with patients with reduced saliva secretion (hyposalivation) or dry mouth (xerostomia). Clinical symptoms as a result of dry mouth vary from mild to severe damage to the hard and soft tissues. Therefore it is important to establish whether a patient is suffering from hyposalivation and if so, whether the patient is able to activate the saliva secretion. Based on saliva testing, hyposalivation and dry mouth can be diagnosed in the general dental practice and be taken into account in prevention and treatment plans.

[Intraoral differences in perceived oral dryness as determined by means of the Regional Oral Dryness Inventory]. / Intraorale verschillen in ervaren monddroogte, bepaald door middel van de Regional Oral Dryness Inventory.

A sensation of dry mouth can be determined with a general questionnaire, the Xerostomia Inventory (XI). This questionnaire, however, does not distinguish among regional differences of oral dryness. In this study, therefore, a new questionnaire was evaluated, the Regional Oral Dryness Inventory (RODI), quantifying the severity of dryness in various intraoral locations. 337 patients participated in this study with an average age of 54 ± 17 years. It appeared there is a significant difference in the sensation of dry mouth between different intraoral locations; the perceived dryness scored highest for the posterior palate and lowest for the floor of the mouth. Introduction of the RODI might help to discriminate among different potential causes of oral dryness in patients. The RODI is highly accessible and easy to carry out in dental practices during routine clinical assessment.

Regional differences in perceived oral dryness as determined with a newly developed questionnaire, the Regional Oral Dryness Inventory.

OBJECTIVES: Several questionnaires, such as the internationally validated and frequently used Xerostomia Inventory (XI), have been developed to quantify the subjective feeling of a dry mouth. These questionnaires quantify the overall perception of dry mouth but lack the possibility to differentiate between various intra-oral regions. In this light, a novel questionnaire, the Regional Oral Dryness Inventory (RODI), which quantifies the severity of dryness at various locations in the mouth, was evaluated. MATERIALS AND METHODS: A retrospective case report study was designed. Data were collected from patients who visited the saliva clinic for Special Care Dentistry in Amsterdam. Data, including the saliva secretion rates, RODI scores, the Xerostomia Inventory (XI) score, and Clinical Oral Dryness Score (CODS), were extracted from the electronic health record system Oase Dental. RESULTS: A total of 337 patients participated in this study with an average age of 54 ± 17 years. The majority of the patients were female (68.5%). The perceived dryness as determined by the RODI was the highest for the posterior palate and the lowest for the floor of the mouth. The highest correlations were found between the corresponding regions in the RODI and regionally related individual items of the XI and CODS. CONCLUSION: There is a significant difference in dry-mouth feeling at different intra-oral locations. CLINICAL RELEVANCE: Regional evaluation of xerostomia with RODI might improve diagnosis of xerostomia by helping to discriminate between different potential causes of oral dryness in patients and for evaluating the efficacy of mouth-moistening products. RODI is highly accessible and easy to perform in dental practices during routine clinical assessment.

[Neoadjuvant and adjuvant treatment of pancreatic cancer]. / Neoadjuvante und adjuvante Therapie beim Pankreaskarzinom.

BACKGROUND: Resection is the only curative treatment option for pancreatic cancer patients. Adjuvant chemotherapy can improve disease-free survival and overall survival after resection. Furthermore, neoadjuvant treatment protocols are currently being investigated in a large number of studies. OBJECTIVE: Summary of the current evidence for adjuvant and neoadjuvant treatment. MATERIAL AND METHODS: Review of the current scientific literature and guidelines. RESULTS AND CONCLUSION: After resection for pancreatic cancer patients should receive intensive chemotherapy with mFOLFIRINOX, gemcitabine plus capecitabine or gemcitabine/5-fluorouracil (5-FU) monotherapy. Neoadjuvant treatment concepts are promising but have to be further evaluated in prospective studies.

[Early oral symptoms of Parkinson's disease]. / Vroege orale symptomen van de ziekte van Parkinson.

A family dentist established that the oral self-care of a 58-year-old man was suddenly inadequate. The dental hygienist who had been recruited subsequently noticed that the dexterity of the man was inadequate. The man's general medical practitioner referred him to a neurologist, who diagnosed Parkinson's disease. Due to this problematic situation, the man was off the family dentist's radar for approximately 1 year. Thereafter, a course of intensive support for his oral health behaviour was initiated. Given the progressivity of Parkinson's disease, it makes sense to aim at an oral health plan resistant to the patient's life course. The family dentist should be aware of his continuing responsibility to provide care and supervision until such time when informal and professional domiciliary care are no longer satisfactory or achievable and admission to a care facility is unavoidable. Only then can the family dentist hand over his responsibility to the geriatric dentist allied to that specific care facility.