Effects of Glycine on Collagen, PDGF, and EGF Expression in Model of Oral Mucositis.

Oral mucositis is frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory, and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in a hamster model oral mucositis. The mucositis was induced by the protocol of Sonis. There were 40 hamsters used, divided into two groups: Group I-control; Group II-supplemented with 5% intraperitoneal glycine, 2.0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation of collagen expression, and the growth factors: Epidermal growth factor (EGF) and platelet (PDGF). It was observed that the group supplemented with glycine experienced higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

Pilot study on the efficacy of combined intraoral and extraoral low-level laser therapy for prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE AND BACKGROUND DATA: Studies suggest that intraoral low-level laser therapy (LLLT) can ameliorate oral mucositis in adult patients receiving high-dose chemotherapy. The objective of this study was to evaluate the use of a combined protocol of intraoral and extraoral LLLT in children undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Twelve children undergoing HSCT were treated four times a week with a combined protocol of intraoral and extraoral LLLT, for a mean duration of 22 days. Clinical and functional mucositis scores were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These scores were compared with a matched retrospective control group of 12 children who did not receive LLLT during HSCT. RESULTS: Clinical mucositis scores were significantly lower in the LLLT group than in the control group (p = 0.004). Incidence of ulcerative oral mucositis was also significantly lower in the LLLT group (p = 0.027). Functional limitation associated with diet/swallowing was less severe in the LLLT group; however, this was not statistically significant. CONCLUSIONS: This study indicates that a combined protocol of intraoral and extraoral application of LLLT can reduce the severity of oral mucositis in pediatric patients undergoing HSCT. Randomized double-blind clinical trials with a larger number of subjects are needed to further test such combined protocols.

Dental anomalies in children submitted to antineoplastic therapy.

Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

Dental anomalies in children submitted to antineoplastic therapy

Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

Facial reconstruction surgery 10 years after treatment for hemangiopericytoma: planning considerations and clinical outcomes.

This paper describes the surgical correction of ankylosis of the right temporomandibular joint and reconstruction of the middle and lower thirds of the right side of the face in a young man who had undergone treatment for hemangiopericytoma 10 years earlier, which led to serious functional, esthetic, and psychological problems and diminished his quality of life. The results of reconstruction surgery with alloplastic material (Medopor®) and surgical planning with fibrotic tissue due to radiation and the risk of osteoradionecrosis are discussed.

Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients.

BACKGROUND: The aim of this study was to review the available literature and define clinical practice guidelines for the use of laser and other light therapies for the prevention and treatment of oral mucositis. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. RESULTS: A new recommendation was made for low-level laser (wavelength at 650 nm, power of 40 mW, and each square centimeter treated with the required time to a tissue energy dose of 2 J/cm(2) (2 s/point)) for the prevention of oral mucositis in adult patients receiving hematopoietic stem cell transplantation conditioned with high-dose chemotherapy, with or without total body irradiation. A new suggestion was made for low-level laser (wavelength around 632.8 nm) for the prevention of oral mucositis in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. No guideline was possible in other populations and for other light sources due to insufficient evidence. CONCLUSIONS: The increasing evidence in favor of low-level laser therapy allowed for the development of two new guidelines supporting this modality in the populations listed above. Evidence for other populations was also generally encouraging over a range of wavelengths and intensities. However, additional well-designed research is needed to evaluate the efficacy of laser and other light therapies in various cancer treatment settings.

Long-term oral effects in patients treated with radiochemotherapy for head and neck cancer.

PURPOSE: The purpose of this study is to assess the late oral complications and the role of salivary gland hypofunction in the severity of mucosal reaction in nonsurgical head and neck cancer patients, submitted to radiotherapy with or without chemotherapy. METHODS AND MATERIALS: Five hundred fifteen charts from patients treated between 2005 and 2009 were reviewed, and 41 patients met the inclusion criteria. Salivary gland function was assessed using a simplified grading system (GSX) and sialometry. Late effects were assessed using the Common Toxicity Criteria (CTC Version 2.0). RESULTS: The average follow-up was 17.1 (4-51) months. A statistical correlation was found for whole salivary flow rates and the average CTC grades for the mucous membrane. Both unstimulated/stimulated whole salivary flow rates (<0.09 mL/min) were identified as potential risk factors (p < 0.05) and an independent predictor for late mucous membrane toxicity (≥ grade 2). A significant correlation was also found between unstimulated salivary flow rates-GSX scores (p = 0.001) and CTC grades for salivary glands. Eighty-five percent of the patients were classified as suffering from salivary gland hypofunction, as well as 58.2 % considered dryness of the mouth the most debilitating complication. CONCLUSIONS: Considering the late effects assessed, the salivary gland hypofunction was the most significant and received the highest morbidity graduation (grade 2/grade 3); xerostomia was also considered the most debilitating complication after treatment. Data show the role of salivary gland hypofunction in the severity of late mucous membrane complication.

Effects of low-level laser therapy on collagen expression and neutrophil infiltrate in 5-fluorouracil-induced oral mucositis in hamsters.

BACKGROUND AND OBJECTIVES: Several studies have suggested that low-level laser therapy (LLLT) can ameliorate oral mucositis; however, the mechanisms involved are not well understood. The aim of this study was to investigate the mechanisms of action of LLLT on chemotherapy-induced oral mucositis, as related to effects on collagen expression and inflammation. MATERIALS AND METHODS: A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil, followed by surface irritation. Animals were randomly allocated into three groups, and treated with an InGaAIP diode laser at a wavelength of 660 nm and output power of 35 or 100 mW laser, or no laser. Clinical severity of mucositis was assessed at four time-points by a blinded examiner. Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points. Collagen was qualitatively and quantitatively evaluated after picrosirius staining. The density of the neutrophil infiltrate was also scored. RESULTS: Peak clinical severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW and control groups. The reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a decrease in the number of neutrophils and an increase in the proportion of mature collagen as compared to the other two groups. The total quantity of collagen was significantly higher in the control (no laser) group at the day 11 time-point, as compared to the 35 mW laser group, consistent with a more prolonged inflammatory response in the control group. CONCLUSION: This study supports two mechanisms of action for LLLT in reducing mucositis severity. The increase in collagen organization in response to the 35 mW laser indicates that LLLT promotes wound healing. In addition, LLLT also appears to have an anti-inflammatory effect, as evidenced by the reduction in neutrophil infiltrate.

Cyclooxygenase-2 and vascular endothelial growth factor expression in 5-fluorouracil-induced oral mucositis in hamsters: evaluation of two low-intensity laser protocols.

GOAL OF WORK: The aim of this study was to investigate the mechanisms whereby low-intensity laser therapy may affect the severity of oral mucositis. MATERIALS AND METHODS: A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil followed by surface irritation. Animals were randomly allocated into three groups and treated with a 35 mW laser, 100 mW laser, or no laser. Clinical severity of mucositis was assessed at four time-points by a blinded examiner. Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points. This tissue was used for immunohistochemistry for cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and factor VIII (marker of microvessel density) and the resulting staining was quantified. MAIN RESULTS: Peak severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW laser and control groups. This reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a significantly lower level of COX-2 staining. The 100 mW laser did not have an effect on the severity of clinical mucositis, but was associated with a decrease in VEGF levels at the later time-points, as compared to the other groups. There was no clear relationship of VEGF levels or microvessel density to clinical mucositis severity. CONCLUSION: The tissue response to laser therapy appears to vary by dose. Low-intensity laser therapy appears to reduce the severity of mucositis, at least in part, by reducing COX-2 levels and associated inhibition of the inflammatory response.

Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients.

OBJECTIVE: A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis (OM) in young patients. BACKGROUND DATA: Besides compromising the patient's nutrition and well-being, oral mucositis represents a portal of entry into the body for microorganisms present in the mouth, which may lead to sepsis if there is hematological involvement. Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment. LLLT appears to be an interesting alternative to other approaches to treating OM, due to its trophic, anti-inflammatory, and analgesic properties. MATERIALS AND METHODS: Patients undergoing chemotherapy (22 cycles) without mucositis were randomized into a group receiving prophylactic laser-irradiation (group 1), and a group receiving placebo light treatment (group 2). Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purposes (group 3, with 10 cycles of CT). Serum granulocyte levels were taken and compared to the progression of mucositis. RESULTS: In group 1, most patients (73%) presented with mucositis of grade 0 (p = 0.03 when compared with the placebo group), and 18% presented with grade 1. In group 2, 27% had no OM and did not require therapy. In group 3, the patients had marked pain relief (as assessed by a visual analogue scale), and a decrease in the severity of OM, even when they had severe granulocytopenia. CONCLUSION: The ease of use of LLLT, high patient acceptance, and the positive results achieved, make this therapy feasible for the prevention and treatment of OM in young patients.