[A PhD completed 9. The value of oral foci screening in oncology patients]. / Hora est 9. De waarde van tandheelkundig focusonderzoek bij oncologiepatiënten.

In both patients who undergo radiotherapy because of a tumour in the head and neck region and patients who are treated with high doses of chemotherapy because of haematological disorders, prior to treatment an oral foci screening is carried out. The aim of this focus investigation is to identify oral abnormalities, the so-called oral foci. Such foci can lead to oral problems during or post-treatment. A careful oral foci screening, conforming to protocol, appears to be very relevant for patients who have to undergo head and neck radiotherapy. Particular attention must be devoted to the evaluation of the perodontium, because the chance of disorders affecting the bone-healing that appear post-radiotherapy in the head and neck region is increased in patients with periodontitis. In patients with a haematological disorder, asymptomatic, chronic foci do not require treatment prior to or during the oncological treatment because such oral foci do not increase an extra risk of infectious complications, despite what was hitherto believed.

Bacterial colonization of the peri-implant sulcus in dentate patients: a prospective observational study.

OBJECTIVES: The aim of the present study was to compare the composition of the periodontal microflora at baseline (T0) with the submucosal microflora at least 1 year after implant placement (T1) in periodontally healthy patients. MATERIAL AND METHODS: For all 169 consecutive patients that visited our clinic during 1 year, we determined their periodontal parameters, implant mucosal index, and presence of implant calculus. At T0, self-reported smoking status was recorded and subgingival and submucosal biofilm samples were obtained and analyzed for the presence and numbers of selected periodontal pathogens. All measurements were repeated at T1. RESULTS: One hundred twenty patients completed the study. Periodontal parameters were stable or had improved at T1. The total bacterial load was lower at implant sites (P < 0.05). The prevalence of Porphyromonas gingivalis was low at baseline, but at T1, detection rate and numbers were higher at implant sites compared to dentate sites. At T1, the frequency of detection of P. gingivalis (P = 0.01), Parvimonas micra (P = 0.018), and Fusobacterium nucleatum (P = 0.035) was higher in smoking patients (n = 23) than in non-smokers (n = 97). CONCLUSIONS: Colonization of the submucosal peri-implant area is similar to the composition of subgingival microbiota. Smoking has a measurable effect on the colonization of implant-associated biofilms and may select for P. gingivalis, P. micra, and F. nucleatum. CLINICAL RELEVANCE: The colonization of implants by well-known periodontal pathogens is very similar to that in normal dentition, also in a healthy cohort. Smoking status was related with the prevalence of periodontal pathogens where smokers harbored more often periodontal pathogens such as P. gingivalis, P. micra, and F. nucleatum.

Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy.

BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. METHODS: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. RESULTS: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. CONCLUSIONS: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy.

The Reproducibility and Applicability of an EFD(®) Dispenser in the Prosthetic Technology of Maxillofacial Prostheses.

A reproducible method of dosing pigments can be beneficial and more efficient in the current colour matching procedure in maxillofacial prosthetics. In this study the reproducibility and applicability for pigment dosing of a commercial available EFD(®) dispenser were tested. The reproducibility of a Performus™ II type EFD(®) dispenser was tested by repeating dosing experiments with a set of eight syringes filled with pigment pastes (Factor 2; Flagstaff, USA). To evaluate conventional colour matching, four conventionally colour matched samples were polymerized and compared to the original ones. To investigate the reproducibility of the dispenser in practice, a fifth recipe was dispensed 10 times and colour differences were evaluated visually and as well calculated from measurements with a colour and translucency meter (CTM, PBSensortechnology bv). All dispensed amounts of pigment pastes showed a coefficient of variation in weight of less than 10 %. Evaluating the reproductions of four skin batches compared to the original batches, a ∆E2000 colour difference of 3-7 was measured. Evaluating ten reproductions of one skin coloured batch made with the dispenser, color difference ∆E2000 values compared to the average L*a*b* values, were less than 2 and no visual colour differences could be estimated. Conform these results, low colour differences could be measured with the CTM, indicating no visually observable consequences. Despite the estimated coefficient of variation, the reproducibility of the EFD(®) dispenser in terms of colour difference ∆E2000 of successive dispensing is applicable for colour reproduction in facial prosthetics. Segregation of the current color pastes in due time needs to be taken into consideration.

The effect of a calcium phosphate mouth rinse on (chemo) radiation induced oral mucositis in head and neck cancer patients: a prospective study.

OBJECTIVES: Promising results of a calcium phosphate (CP) mouth rinse on reduced severity of oral mucositis have been reported. The aim of this study was to determine the effect of a CP mouth rinse on the frequency, duration and severity of (chemo) radiation induced oral mucositis in patients with head-neck cancer. MATERIAL AND METHOD: patients with oral malignancies, treated with (chemo) radiotherapy, were included. Patients rinsed four times a day with a CP mouth rinse. Patients not willing to rinse with the CP mouth rinse served as control. Mucositis was scored according to the WHO score at baseline and twice a week during the full course of (chemo) radiotherapy. Patient's self-reported mouth-throat soreness (MTS) was evaluated at the same time interval using a diary in the CP mouth rinse group. The outcomes on MTS were compared with a historical control group. RESULTS: Fifty-two patients were analysed: 25 CP mouth rinse group, 11 control group and 16 historical group. There was no significant difference between the CP group and control group on development and severity of oral mucositis. No significant difference was found for subjective outcomes on MTS between the CP group and the historical group. CONCLUSIONS: The CP mouth rinse seems to have no influence on the frequency, duration and severity of oral mucositis during (chemo) radiation in patients with head and neck cancer. A trend to develop less MTS for drinking and eating was found when applying the CP mouth rinse.

Stem cells and the repair of radiation-induced salivary gland damage.

Hyposalivation underlying xerostomia after radiotherapy is still a major problem in the treatment of head and neck cancer. Stem cell therapy may provide a means to reduce radiation-induced hyposalivation and improve the quality of life of patients. This review discusses the current status in salivary gland stem cell research with respect to their potential to attenuate salivary gland dysfunction. Knowledge on the embryonic development, homeostasis and regeneration after atrophy of the salivary glands has provided important knowledge on the location of the salivary gland as well as on the factors that influence proliferation and differentiation. This knowledge has helped to locate, isolate and characterize cell populations that contain the salivary gland stem cell, although the exact tissue stem cell is still unidentified. The role that stem/progenitor cells play in the response to radiation and the factors that can influence stem/progenitor induced proliferation and differentiation are discussed. Finally, the mobilization and transplantation of stem cells and supportive cells and their potential to attenuate radiation-induced salivary gland damage are discussed. Based on the major advances made in the field of stem cell research, stem cell-based therapy has great potential to allow prevention or treatment of radiation-induced hyposalivation.

[Haematopoietic stem cell transplantation and oral complications]. / Hematopoëtische stamceltransplantaties en orale problemen.

New haematopoietic stem cell transplantation procedures make the treatment available to patients who previously did not qualify, such as the elderly. In addition, the spectrum of oral complications associated with haematopoietic stem cell transplantation has altered as a result of the recent developments. This article is a review of the main principles of haematopoietic stem cell transplantation and provides information on oral complications which may develop, such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia, hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and growing and developing disturbancies. Finally, the role of dental care providers in cases of haematopoietic stem cell transplantation is addressed.

[Foci of infection and oral supportive care in cancer patients]. / Focusonderzoek en mondverzorging bij patiënten met kanker.

Radiation therapy in the head and neck area and treatment with high dose chemotherapy entail damage to healthy tissue in the mouth. In order to reduce to a minimum the chances of these side effects of cancer treatment developing, it is necessary to carry out oral foci tests prior to oncological therapy. In addition supplementary oral and dental care measures seem to be important in order to limit the side effects of oncological therapy on the teeth, salivary glands and jaw as much as possible. This supportive oral care is not only necessary during, but also for years after the oncology treatment. Therefore not only dental professionals affiliated to oncology teams will have to take care of cancer patients, but also family dentists and dental hygienists.

The role of oral mucositis on the systemic inflammation parameter IL-8 in febrile neutropenic cancer patients.

PURPOSE: Cancer patients treated with cytostatic drugs often develop oral mucositis, considered to be a mucosal injury in which various cytokines, such as interleukin 8 (IL-8), may play a role. Plasma IL-8 is a systemic inflammatory response parameter. This study investigated whether oral mucositis affects plasma IL-8 levels in febrile neutropenic cancer patients. PATIENTS AND METHODS: Patients (n = 57) who were hospitalized with chemotherapy-induced neutropenic fever were scored for oral mucositis on the second day of hospitalization according to a validated oral mucositis assessment scale (OMAS) and WHO toxicity grading. Patients (n = 20) with a clinical sepsis or local bacterial infection were excluded from this evaluation. The remaining 37 patients were divided in groups with and without oral mucositis. RESULTS: The difference in plasma IL-8 level between patients with and without mucositis was not significant (P = 0.7). Similarly no difference was observed in the degree and duration of granulocytopenia. CONCLUSION: These results indicate that low-grade oral mucositis is not related to the systemic plasma IL-8 level in febrile neutropenic cancer patients without a clinical sepsis or local bacterial infection.

Preventive intervention possibilities in radiotherapy- and chemotherapy-induced oral mucositis: results of meta-analyses.

The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of randomized controlled clinical studies, published between 1966 and 2004, the aim of which was the prevention of mucositis in cancer patients undergoing head and neck radiation, chemotherapy, or chemoradiation. The control group consisted of a placebo, no intervention, or another intervention group. Mucositis was scored by either the WHO, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) score, or the absence or presence of ulcerations, or the presence or absence of grades 3 and 4 mucositis. The meta-analyses included 45 studies fulfilling the inclusion criteria, in which 8 different interventions were evaluated: i.e., local application of chlorhexidine; iseganan; PTA (polymyxin E, tobramycine, and amphotericin B); granulocyte macrophage-colony-stimulating factor/granulocyte colony-stimulating factor (GM-CSF/G-CSF); oral cooling; sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G-CSF. Four interventions showed a significant preventive effect on the development or severity of oral mucositis: PTA with an odds ratio (OR) = 0.61 (95% confidence interval [CI], 0.39-0.96); GM-CSF, OR = 0.53 (CI: 0.33-0.87); oral cooling, OR = 0.3 (CI: 0.16-0.56); and amifostine, OR = 0.37 (CI: 0.15-0.89). To date, no single intervention completely prevents oral mucositis, so combined preventive therapy strategies seem to be required to ensure more successful outcomes.

Assessment of oral mucositis in clinical trials: impact of training on evaluators in a multi-centre trial.

In the assessment of mucositis, the inter-evaluator variability needs to be minimised and would likely to be best accomplished by training. The aim of this study was to evaluate the effect of training on concordance of evaluators in scoring oral mucositis. The evaluators were informed about the pathobiology and clinical appearance of mucositis and were trained in scoring mucositis according the Oral Mucositis Assessment Scale (OMAS). The effect of the training was evaluated by a pre- and post-training test. Each test consisted of 15 slides depicting oral mucositis. The pre- and post-training scores were compared to the reference standard. During 8 months at 6 meetings, 65 evaluators were trained. The mean percentage correctly scored slides according the OMAS increased significantly between the pre- and post-training test (P<0.001). Training evaluators in scoring oral mucositis has a significant improvement on the outcome of mucositis assessment.

Clinical effects of flurbiprofen tooth patch on radiation-induced oral mucositis. A pilot study.

BACKGROUND: Mucositis is an oral sequela of radiotherapy. In the development of mucositis several mechanisms play a role, such as inflammation and the effect of radiation on the high proliferation rate of oral basal epithelial cells. Therefore, administration of a drug with antiinflammatory and antiproliferative properties might delay the disorder and/or alleviate the severity of oral mucositis. The aim of this pilot study was to evaluate the effect of flurbiprofen in a tooth patch on the development, severity and duration of pseudomembranous mucositis in patients treated with curative head and neck radiotherapy. METHODS: The study group comprised 12 patients with a malignant tumor in the head and neck region to be treated with primary curative or postoperative radiotherapy. Patients applied once a day before sleep a flurbiprofen tooth patch to a natural tooth or upper denture during the full course of radiotherapy, starting 1 week before the onset of radiotherapy. Oral mucositis, pain, feeding, body weight and viability and maturation of epithelial cells were assessed. The results were compared with the findings in a historical control group. RESULTS: No differences were found for severity and duration of pseudomembranous mucositis between the two groups. The onset of pseudomembranous/ulcerative mucositis occurred later in the flurbiprofen group (14.6+/-3.8 days, mean+/-SD) than in the historical control group (11+/-3.5 days; P<0.05). CONCLUSION: This study shows that the flurbiprofen 15 mg tooth patch cannot prevent the development of pseudomembranous mucositis and has no influence on the duration of oral mucositis.

Outcome of local application of amifostine (WR-1065) on epirubicin-induced oral mucositis. A phase II study.

BACKGROUND: Intravenous administration of amifostine reduces chemotherapy-induced toxicity. Preclinical experiments showed a reduction in radiation-induced mucositis after local application of the active metabolite of amifostine (WR-1065). This study evaluated the effect of local application of WR-1065 on chemotherapy-induced oral mucositis. PATIENTS AND METHODS: Non-small cell lung cancer patients treated with gemcitabine and epirubicin every 3 weeks for a maximum of five cycles were included. WR-1065 was administered during the second and third cycle as an oral rinse. Oral mucositis evaluation included WHO toxicity grading, a validated oral mucositis assessment scale (OMAS) and a questionnaire. RESULTS: Twenty-four patients were evaluated for at least one control and one rinse cycle. Mucositis scores, pain and feeding difficulties increased from day 1 to day 15, and were not significantly different between the control and rinse cycles. Local application of WR-1065 leads to detectable quantities of WR-1065 in epithelial mucosa cells. A negative correlation between the WR-1065 concentration and OMAS score was found. CONCLUSION: No clinical detectable influence of WR-1065 on oral mucositis was found.

Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial.

Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial. Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative radiotherapy participated in this study. The patients received either the active lozenges of 1 g containing polymyxin E 2 mg, tobramycin 1.8 mg and amphotericin B 10 mg (PTA) (33 patients) or the placebo lozenges (32 patients), four times daily during the full course of radiotherapy. Mucositis, changes in the oral flora, quality of feeding and changes of total body weight were assessed. Mucositis score did not differ between the groups during the first 5 weeks of radiotherapy. Nasogastric tube feeding was needed in six patients (19%) of the placebo group and two patients (6%) of the PTA group (P=0.08). Mean weight loss after 5 weeks of radiation was less in the PTA group (1.3 kg) (s.d.: 3.0) than in the placebo group (2.8 kg) (s.d.: 2.9) (P=0.05). Colonisation index of Candida species and Gram-negative bacilli was reduced in the PTA group and not in the placebo group (P<0.05). No effect on other microorganisms was detected. In conclusion, selective oral flora elimination in head and neck irradiation patients does not prevent the development of severe mucositis.

Quantification of oral mucositis due to radiotherapy by determining viability and maturation of epithelial cells.

BACKGROUND: An in-vitro assay has been developed for quantitative assessment of chemotherapy induced oral mucositis. In the present study this method was evaluated for assessment of irradiation mucositis at a cellular level. METHODS: Ten patients participated in this consecutive study. All patients were treated with conventional fractionated curative postoperative radiotherapy. Prior to, and weekly during, the irradiation course, oral washings were obtained to determine viability of epithelial cells by trypan blue dye exclusion. Maturation of epithelial cells was assessed from smears (Papanicolaou staining). The viability data were compared with the WHO-score for mucositis. RESULTS: Epithelial cell viability increased during the first three weeks of radiation (P = 0.04), and was seen earlier than the subjective mucosal changes with the WHO-score. Cell maturity shifted from immature and intermediate to mature (P = 0.03). CONCLUSIONS: The cell viability assay can be considered an objective method for following the development of irradiation mucositis, and seems to be more sensitive during the first three weeks of irradiation than the WHO-scoring method.

Parotid and submandibular/sublingual salivary flow during high dose radiotherapy.

It was studied whether differences in acute radiosensitivity exist between parotid and submandibular/sublingual glands. The results revealed that salivary flow rates decreased dramatically during the first 2 weeks of radiotherapy. Neither recovery nor significant differences were observed between the production of saliva from the parotid and submandibular/sublingual glands during the 13 weeks observation period.