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.

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.

[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.

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.

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.

[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.

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.

[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.

[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.

[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.

[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.

U-CH17P, -M and -S, a new cell culture system for tumor diversity and progression in chordoma.

Chordoma is a rare bone tumor with a known intrinsic heterogeneity. Here, we address this tumor heterogeneity in a new cell culture model for tumor diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumor tissues revealed that the precursor cells of U-CH17P, U-CH17M and U-CH17S were already present in the primary tumor. Therefore, we show that clonal diversity of this chordoma exists in the primary tumor and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumor progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology.

Tooth loss in Sjögren's syndrome patients compared to age and gender matched controls.

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.

Resistance training as supportive measure in advanced cancer patients undergoing TKI therapy-a controlled feasibility trial.

PURPOSE: While there is growing evidence for positive effects of progressive resistance training in curatively treated cancer patients, data on advanced cancer patients are scarce. This pilot study aimed at investigating for the first time feasibility and effects of progressive resistance training in advanced cancer patients undergoing tyrosine kinase inhibitor (TKI) therapy. METHODS: Patients starting a TKI-based anti-tumor therapy were assigned to a resistance training group (RT, 12 weeks of progressive machine-based resistance training 2×/week) or a control group (CON, treatment as usual) until 10 patients had finished in each group (RT 80% males, 90% renal cell carcinoma, 65 ± 11 years, CON 80% males, 70% renal cell carcinoma, 61 ± 6 years). Primary endpoint was feasibility. Furthermore, fatigue (MFI), quality of life (QoL, EORTC QLQC30), and muscle strength were assessed. Testing occurred at baseline and after 12 weeks. RESULTS: Training was feasible in 9 out of 10 participants and no serious adverse events occurred. It had beneficial effects on muscle strength (maximum voluntary isometric contraction of the quadriceps: RT +11 ± 9 Nm, CON -13 ± 25 Nm, p = 0.005), but not on fatigue (general fatigue score RT +0.3 ± 4.1, CON -1.5 ± 3.0, p = 0.223) or QoL (global QoL score RT -5.6 ± 16.1, CON -2.0 ± 18.2, p = 0.617). CONCLUSIONS: Progressive machine-based resistance training appears feasible in the majority of advanced cancer patients undergoing TKI therapy. However, its positive effects on muscle strength do not seem to be associated with positive effects on fatigue or quality of life. Future studies should therefore compare whether home-based training is more beneficial for patient-reported outcomes. TRIAL REGISTRATION: NCT01645150.

[Durable remission under dual HER2 blockade with Trastuzumab and Pertuzumab in a patient with metastatic gallbladder cancer]. / Dauerhafte Remission unter dualer HER2-Blockade mit Trastuzumab und Pertuzumab bei metastasiertem Gallenblasenkarzinom.

Gallbladder cancer represents a rare but dismal disease. The only curative option is complete surgical resection, though patients often develop recurrent disease. In patients with advanced biliary tract cancer, the combination of cisplatin and gemcitabine showed a benefit in overall survival compared to gemcitabine alone. However, there is no standardized second-line regimen after treatment failure. We report on a young patient with early recurrence of a gallbladder cancer with cutaneous and peritoneal metastases. Upon identification of an ERBB2 gene amplification within the NCT MASTER (Molecularly Aided Stratification for Tumor Eradication Research) exome sequencing program with resulting overexpression of HER2 in the tumors cells, the patient received a targeted therapy with the HER2 antibodies pertuzumab and trastuzumab in combination with nab-paclitaxel, which led to a durable remission for more than one year. This case report underlines the potential of molecularly aided personalized targeted therapy for patients with biliary tract cancer and the need for respective clinical trials.

Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. METHODS: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method. RESULTS: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. CONCLUSIONS: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.

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

This article is temporarily under embargo.

Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Outcome analysis and comparison with a 3D-treated patient cohort.

BACKGROUND: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT. RESULTS: Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy. CONCLUSION: IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.