Dental Pulp Stem Cells for Salivary Gland Regeneration-Where Are We Today?

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.

The impact of COVID-19 on oral squamous cell carcinoma's diagnostic stage-A retrospective study.

OBJECTIVE: The COVID-19 pandemic has had an impact on patients' access to primary care services. A timely diagnosis of oral squamosa cell carcinoma is paramount. This study aims to quantify the pandemic's effect on tumor volume at the time of initial diagnosis. MATERIALS AND METHODS: In a retrospective study, all primarily diagnosed cancer patients between March 2018 and March 2022 were compiled; the TNM stage and the tumor volume were evaluated. Tumor volumes were calculated using pathology or radiology reports. RESULTS: In total, 162 newly diagnosed tumor cases were included in this study. Of these, 76 (46.9%) cases were allocated in the "pre-COVID-19" group and 86 (53.1%) in the "COVID-19" group. Patients diagnosed during the "COVID-19" period showed a significantly advanced T stage (p < 0.001) and larger mean tumor volumes (53.16 ± 73.55 cm3 vs. 39.89 ± 102.42 cm3 ; p = 0.002) when compared to the control group. CONCLUSION: Tumor volume and T stage were significantly advanced in the "COVID-19" group when compared to prepandemic data. We hypothesize that the postponement of routine dental check-ups may explain this finding. Hence, dentists and primary care providers are encouraged to place particular emphasis on screening during routine check-ups.

Socioeconomic Status-Related Parameters as Predictors of Competing (Non-Bladder Cancer) Mortality after Radical Cystectomy.

OBJECTIVE: To investigate the impact of socioeconomic status-related parameters on competing (non-bladder cancer) mortality after radical cystectomy. PATIENTS AND METHODS: A total of 1,268 consecutive patients who underwent radical cystectomy for urothelial or undifferentiated bladder cancer at our institution between 1993 and 2016 with a mean age of 69 years (median 70 years) were studied. The mean -follow-up of the censored patients was 7.2 years (median 5.7 years). Proportional hazard models for competing risk were used to identify predictors of non-bladder cancer (competing) mortality. The following parameters were included into multivariate analyses: age, American Society of Anesthesiologists physical status classification, Charlson score, gender, level of education, smoking status, marital status, local tumour stage, lymph node status, adjuvant and neoadjuvant chemotherapy. RESULTS: Besides age and both comorbidity classifications, the socioeconomic status-related parameters gender (female versus male, hazard ratio [HR] 0.58, 95% CI 0.40-0.84, p = 0.0042), level of education (university degree or master craftsman versus others, HR 0.76, 95% CI 0.56-0.1.03, p = 0.0801), smoking status (current smoking versus others, HR 1.47, 95% CI 1.10-1.96, p = 0.0085) and marital status (married versus others, HR 0.68, 95% CI 0.50-0.92, p = 0.0133) were independent predictors of competing mortality after radical cystectomy. If considered in combination (multiplication of HRs), the prognostic impact of socioeconomic parameters superseded that of the investigated comorbidity classifications. CONCLUSION: Socioeconomic status-related parameters may provide important information on the long-term competing mortality risk after radical cystectomy supplementary to chronological age and comorbidity.

PIK3CA Hotspot Mutations in Saliva as a Diagnostic Marker in Oral Squamous Cell Carcinoma Patients.

BACKGROUND/AIM: This study aimed at the analogous detection of PIK3CA mutations, common in oral squamous cell carcinoma (OSCC), in matched tumor and saliva samples. PATIENTS AND METHODS: Tissue and saliva samples were obtained from 29 patients diagnosed with primary OSCC. Saliva samples were obtained preoperatively; tissue specimens were acquired during tumor resection. Tumor DNA was extracted from both tissue and saliva samples. All samples were controlled for DNA quantity and quality and genetic matching of sample pairs was confirmed using the iPlex Pro Exome QC Panel. Variant detection was performed using the MassARRAY® System, a mass-spectrometry based detection system. Mutational analysis in tissue tumor DNA was made using the multiplexed ClearSEEK™ PIK3CA v1.0 Panel covering 20 hotspot mutations in PIK3CA. In saliva samples, variants were analyzed using both the ClearSEEK™ and the UltraSEEK® Lung v1.1 Panel, with a higher limit of detection but covering less PIK3CA variants. RESULTS: Overall, a PIK3CA variant was found in seven of the 29 tumor tissue samples (24%) by ClearSEEK™; UltraSEEK® additionally confirmed the variant in four of these seven positive samples. Of the three variants not detected by UltraSEEK®, two were not included in the panel and one was included but not detected. Of the seven variants found in tissue, five could also be detected in the matching saliva samples (71%), either by utilizing ClearSEEK™ or UltraSEEK® Conclusion: The detection of PIK3CA hotspot mutations in OSCC and their simultaneous occurrence in saliva underline the potential benefit of liquid biopsies for non-invasive cancer detection and follow-up care of OSCC patients.

Three-Dimensional Plotted Calcium Phosphate Scaffolds for Bone Defect Augmentation-A New Method for Regeneration.

For sinus grafting, different methods and materials are available. One possible shortcoming of particulate bone grafts is either overfilling or augmenting the planned implant area insufficiently. To overcome this risk and to determine the implant position prior augmentation, we present an approach using three-dimensional printed scaffolds. A patient with a remaining anterior dentition and bilateral severely atrophied posterior maxilla was seeking oral rehabilitation. The cone beam computed tomography (CBCT) showed residual bone heights between one and two millimeters. Following the three-dimensional reconstruction of the CBCT data, the positions of the implants were determined in areas 16 and 26. Three-dimensional scaffolds adapted to the topography of the sinus were virtually designed and printed using a calcium phosphate cement paste. Bilateral sinus floor augmentation applying the printed scaffolds with an interconnecting porosity followed. After nine months, a satisfying integration of the scaffolds was obvious. At the re-entry, vital bone with sufficient blood supply was found. One implant could be placed in positions 16 and 26, respectively. After five months, the implants could be uncovered and were provided with a temporary denture. The application of three-dimensionally printed scaffolds from calcium phosphate cement paste seems to be a promising technique to graft the severely atrophied posterior maxilla for the placement of dental implants.

Socioeconomic disparities between oral cavity cancer patients in Germany.

Objective: In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany. Patients and methods: In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence. Results: Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival. Conclusion: Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups.

Adapting the Pore Size of Individual, 3D-Printed CPC Scaffolds in Maxillofacial Surgery.

Three dimensional (3D) printing allows additive manufacturing of patient specific scaffolds with varying pore size and geometry. Such porous scaffolds, made of 3D-printable bone-like calcium phosphate cement (CPC), are suitable for bone augmentation due to their benefit for osteogenesis. Their pores allow blood-, bone- and stem cells to migrate, colonize and finally integrate into the adjacent tissue. Furthermore, the pore size affects the scaffold's stability. Since scaffolds in maxillofacial surgery have to withstand high forces within the jaw, adequate mechanical properties are of high clinical importance. Although many studies have investigated CPC for bone augmentation, the ideal porosity for specific indications has not been defined yet. We investigated 3D printed CPC cubes with increasing pore sizes and different printing orientations regarding cell migration and mechanical properties in comparison to commercially available bone substitutes. Furthermore, by investigating clinical cases, the scaffolds' designs were adapted to resemble the in vivo conditions as accurately as possible. Our findings suggest that the pore size of CPC scaffolds for bone augmentation in maxillofacial surgery necessarily needs to be adapted to the surgical site. Scaffolds for sites that are not exposed to high forces, such as the sinus floor, should be printed with a pore size of 750 µm to benefit from enhanced cell infiltration. In contrast, for areas exposed to high pressures, such as the lateral mandible, scaffolds should be manufactured with a pore size of 490 µm to guarantee adequate cell migration and in order to withstand the high forces during the chewing process.