Preliminary study in a new protocol for the treatment of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT).

Oral mucositis (OM) is a debilitating and serious side effect in patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT). Laser therapy is becoming a promising treatment option in these patients, avoiding the necessity of enteral/parenteral nutrition. The aim of this study was to evaluate the efficacy of laser therapy in patients affected by oral mucositis induced by chemotherapy and HSCT. Sixteen onco-hematological pediatric patients receiving chemotherapy and hematopoietic stem cell transplantation, affected by oral mucositis, were enrolled in this study. They were divided in two randomized groups: the laser group and the placebo-control group. Patients in the laser group were treated with HPLT (970 ± 15 nm, 3.2 W (50%), 35-6000 Hz, 240 s) for four consecutive days, once a day; and placebo group underwent sham treatment. The assessment of mucositis was recorded through WHO Oral Mucositis Grading Objective Scale, and pain was evaluated through Visual Analogue Scale (VAS). Patients were monitored and evaluated 3, 7, and 11 days after the first day of laser therapy. Once OM was diagnosed, the patients had mucositis grading assessments before laser or sham application at day 3, 7, and 11 after first application. All patients of laser group demonstrated improvement in pain sensation from day 3 after first application of laser (p < 0.05), ulcerations reduced their dimensions and erythema disappeared. The patients of placebo group had improvement from day 7. In laser group, all mucositis were fully resolved from day 7 (p < 0.05). Oral mucositis negatively impacts on nutritional intake, oral hygiene, and quality of life. Laser therapy appears to be a safe and innovative approach in the management of oral mucositis. In this preliminary study, HPLT encourages to consider laser therapy as a part of onco-hematological protocol, providing to decrease pain and duration of OM induced by CT and HSCT. Further researches will be needed, especially randomized, controlled clinical trials with a large number of enrolled patients and a long term of follow-up to confirm the efficacy of laser therapy in prevention and control of OM in onco-hematological pediatric patients.

[Lesions of the oral mucosa : Differential diagnostic approach from the maxillofacial surgeon's perspective]. / Schleimhauterkrankungen : Differenzialdiagnostischer Zugang aus kieferchirurgischer Sicht.

A detailed medical history and a careful clinical examination are the basis for developing a list of possible differential diagnoses in lesions of the oral mucosa. On this basis, it can be decided whether a lesion can be observed for 14 days after removal of possible causes or the start of a trial treatment, or whether a biopsy for histological examination must be taken immediately. An excisional biopsy is performed for small and presumably benign lesions, an incisional biopsy for large and presumably malignant lesions. If an autoimmune blistering disease is suspected, a second sample for examination by immunofluorescence is taken. Depending on the results of the histological examination further treatment steps are planned or regular appointments for follow-up are arranged.

Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study.

Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation.

BACKGROUND AND PURPOSE: Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. MATERIAL AND METHODS: Daily fractionated irradiation (5 × 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. RESULTS: Transplantation of 6 × 10(6), but not of 3 × 10(6) bone marrow stem cells on day - 1, + 4, + 8, + 11 or + 15 significantly increased the ED50 values (dose, at which an ulcer is expected in 50 % of the mice); transplantation on day + 2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day - 1, 2 or + 8 significantly, and on day + 4 marginally increased the ED50 values. CONCLUSION: Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation.

Therapy of peri-implant diseases. Where is the evidence?

Peri-implant diseases are a common problem in dentistry today and no definitive treatment protocol exists for their treatment. The purpose of this review was to examine the evidence concerning the management of these diseases. The evidence provided suggests that peri-mucositis can be managed with use of mechanical nonsurgical therapy. Peri-implantitis does not respond to nonsurgical therapy. Various surgical methods have been proposed for management of peri-implantitis with some success; however, no single method can be promoted based on the current evidence.

[Use of erbium laser for treatment of dental implant complications].

The paper presents the results of the use of Er:YAG laser for surgical treatment of 48 patients aged 25-73 years with early and late dental implant complications were presented. Among all lasers used in the field of dentistry, the Er:YAG laser seems to possess characteristics most suitable for oral treatment, due to its ability to ablate both soft and hard tissues as well as bacterial biofilms and calculus without causing major thermal damage to the adjacent tissue.

Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta).

BACKGROUND: A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. METHODS: To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. RESULTS: Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin-resistant Staphylococcus aureus infection. Vancomycin and ampicillin-sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. CONCLUSIONS: Simian noma associated with methicillin-resistant Staphylococcus aureus (MRSA) had not previously been reported in non-human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.

Maxillary osteomyelitis in two Scottish terrier dogs with chronic ulcerative paradental stomatitis.

Two Scottish terrier dogs were presented for recurrent oral problems. They were diagnosed with refractory chronic ulcerative paradental stomatitis and necrosis of the incisive and maxillary bones. Both dogs were treated with a combination of bilateral rostral maxillectomy and tooth extractions. The ostectomy was performed with a specific cutting device using piezoelectric bone surgery technology. These two cases show that a precise evaluation of dogs is essential for the diagnose of chronic ulcerative paradental stomatitis and its differentiation from mucocutaneous autoimmune diseases.

Diagnosis of peri-implant status after peri-implantitis surgical treatment: Proposal of a new classification.

BACKGROUND: The 2017 World Workshop classified peri-implant diseases into health, peri-implant mucositis, and peri-implantitis. The aim of this article is to build upon this recent classification and propose a framework for the diagnosis of peri-implant status after surgical treatment for peri-implantitis. METHODS: A literature review was conducted to discuss the relevant diagnostic, clinical, and radiographic parameters, including probing depth, bleeding on probing, visual inspection, and radiographic bone loss. Case definitions of possible treatment outcomes were discussed, and a flowchart was constructed to guide post-treatment diagnosis according to the possible clinical scenarios which can be encountered in daily practice. RESULTS: Three possible treatment outcomes were identified after resective treatment of peri-implantitis: 1) peri-implant health with a reduced support, 2) peri-implant mucositis with a reduced support, and 3) recurrent/refractory peri-implantitis. After regenerative treatment for peri-implantitis, the peri-implant condition was classified according to the same diagnoses with the addition of peri-implant health or peri-implant mucositis after complete regeneration for cases where complete regeneration was attained. Criteria for successful treatment of peri-implantitis were proposed. After resective therapy, a successful treatment outcome was defined as peri-implant health with a reduced support, whereas, after regenerative therapy, a successful outcome was described as either peri-implant health after complete regeneration or peri-implant health with a reduced support. CONCLUSIONS: The proposed classification system of peri-implant status after surgical treatment for peri-implantitis provides a framework for diagnosing the various forms of peri-implant stability or disease to guide clinical decision-making post-treatment.

Feline chronic gingivostomatitis is more prevalent in shared households and its risk correlates with the number of cohabiting cats.

OBJECTIVES: The aim of this study was to determine whether feline chronic gingivostomatitis (FCGS) is more prevalent in shared vs single-cat households, whether the number of cohabiting cats or outdoor access represent risk factors for FCGS and whether the number of cohabiting cats is a useful prognostic indicator for standard surgical treatment. METHODS: Cats diagnosed with FCGS (study group) in the past 5 years at a referral institution were identified. The number of cohabiting cats, outdoor access, number of other cohabiting cats diagnosed with FCGS, ⩾6 month surgical outcome, when applicable, and historical signs of upper respiratory disease among any of the cohabiting cats, as well as patient demographic information, were recorded. Data were collected from medical records and by means of a telephone interview with the owners. The same information was collected from a group of cats of similar demographic characteristics diagnosed with periodontal disease but free of FCGS (control group). RESULTS: Seventy-six cats were included, of which 36 (47%) had FCGS and 40 (53%) served as controls. Bivariate analysis showed that cats with FCGS were significantly more likely to come from shared households, and had significantly more total cats per household compared with controls. Multivariate analysis also showed that cats in shared households had a significantly increased odds of FCGS compared with those from single-cat households. Historical signs of upper respiratory disease and outdoor access among cats within the same household were not associated with FCGS. The number of cohabiting cats was not associated with surgical outcome. CONCLUSIONS AND RELEVANCE: Cats with FCGS are more likely to live in shared households. The risk of FCGS correlates with the number of cohabiting cats. The epidemiological features of FCGS may support an infectious etiology. The number of cohabiting cats within a household is not a useful prognostic indicator for standard surgical treatment of FCGS.

Long time follow up of implant therapy and treatment of peri-implantitis.

Dental implants have become an often used alternative to replace missing teeth, resulting in an increasing percentage of the adult population with implant supported prosthesis. Although favourable long-term results of implant therapy have been reported, infections occur. Until recently few reports included data on peri-implant infections, possibly underestimating this complication of implant treatment. It is possible that some infections around implants develop slowly and that with time peri-implantitis will be a common complication to implant therapy as an increasing number of patients have had their implants for a long time (>10 years). Data on treatment of peri-implant lesions are scarce leaving the clinician with limited guidance regarding choice of treatment. The aim of this thesis was to study the frequency of implant loss and presence of peri-implant lesions in a group of patients supplied with Brånemark implants 9-14 years ago, and to relate these events to patient and site specific characteristics. Moreover three surgical treatment modalities for peri-implantitis were evaluated. The thesis is based on six studies; Studies I-III included 218 patients and 1057 implants followed for 9-14 years evaluating prevalence of, and factors related to implant loss (Paper I) and prevalence of peri-implant infections and related factors (Paper I-III). Study IV is a review describing different treatment modalities of peri-implant infections. Study V is a prospective cohort study involving 36 patients and 65 implants, evaluating the use of a bone substitute with or without the use of a resorbable membrane. Study VI is a case series with 12 patients and 16 implants, evaluating a bone substitute in combination with a resorbable membrane and submerged healing. This thesis demonstrated that: After 9-14 years the survival rates of dental implants are high (95.7%). Implant loss seems to cluster within patients and are related to periodontitis evidenced as bone loss on radiographs at remaining teeth before implant placement. (Paper I) Peri-implantitis is a common clinical entity after 9-14 years. (Paper II) Using the implant as the statistical unit the level of keratinized mucosa and pus were explanatory for a bone level at > or =3 threads (1.8 mm). When the patient was used as a statistical unit a history of periodontitis and smoking were explanatory for peri-implantitis. (Paper III) Animal research has demonstrated that re-osseointegration can occur. The majority of human studies were found to be case reports. Using submerged healing and bone transplants, bone fill can occur in peri-implant defects. (Paper IV) Surgical treatment of peri-implantitis using a bone substitute with or without a resorbable membrane resulted in similar pocket depth reduction, attachment gain and defect fill. (Paper V) Bone substitute in combination with a resorbable membrane and a submerged healing resulted in defect fill > or =2 threads (1.2 mm) in 81% of the implants. (Paper VI) In conclusion: 9-14 years after implant installation peri-implant lesions are a common clinical entity. Smokers and patients with a history of periodontal disease are at higher risk to develop peri-implantitis. Clinical improvements and defect fill can be obtained with various surgical techniques using a bone substitute.

Cement-associated peri-implant mucositis. A 1-year follow-up after excess cement removal on the peri-implant tissue of dental implants.

BACKGROUND: Methacrylate-based cements seem to promote peri-implant tissue inflammation even in the absence of excess cement. PURPOSE: The present study deals with the question of whether the removal of methacrylate cement from the peri-implant sulcus will lead to peri-implant tissues free of inflammation on a 1-year follow-up basis. MATERIAL AND METHODS: Implant supported suprastructures that had been in the mouth for at least 3.5 years either cemented with methacrylate (premier implant cement [PIC]) or zinc eugenol (temp bond [TB]) cement were compared. All superstructures in 33 patients with a total of 61 implants (35 with PIC and 26 with TB) were removed and excess cement, bleeding on probing (BOP), suppurationen and probing depth were documented. Excess cement found was removed, and in all cases the suprastructure was recemented with TB. Patients were followed up after 4 weeks (F1) and 1 year (F2). RESULTS: Excess cement was found around 60% of the implants with PIC. No excess cement was found around implants with TB. At the time of revision therapy, BOP was found around 100% of the implants with PIC and excess cement (PIC+), 93% around implants with PIC but no excess cement (PIC-), and around 42% of the TB-cemented implants (Chi-squared P < .01). Suppuration was observed in 86% of the PIC+ implants, in 14% of the PIC- implants and in 0% of the TB implants (Chi-squared P < .01). At the time of both F1 and F2, the inflammation parameters, that is BOP and suppuration, on implant level were significantly reduced in the PIC+ cases (McNemar's test P < .01). For PIC-, BOP was significantly reduced at both points in time (P < .05). For TB no differences were found. Probing depth at F2 had significantly decreased in all groups (t test P < .05). CONCLUSION: The removal of excess cement and recementation with TB had an anti-inflammatory effect on the peri-implant tissues after 1 year.

Assessment of the effectiveness of peripheral administration of morphine with local articaine anaesthesia for surgery in inflamed oral and maxillofacial tissues.

The controversy surrounding clinical trials of peripherally applied morphine with local anaesthetic and the attendant ambiguous results led to a study of our own clinical material. The aim of the study was to assess the effectiveness of peripheral administration of morphine with local articaine anaesthesia in inflamed oral and maxillofacial tissues. Sixty patients who qualified for the randomized, double-blinded study were randomly divided into two groups. Group 'LA' received a standard local anaesthetic solution (articaine plus epinephrine) while group 'LA-Mo' received the standard solution with an addition of 1 mg of morphine. Pain intensity was assessed using the Visual Analogue Scale, before and directly after surgery as well as at 1, 2, 6, 12, 24 and 48 h after completion of surgery. Furthermore, supplemental consumption of the prescribed analgesic was recorded. Despite a very similar average level of initial pain, there was a marked difference between the groups in the pain level during surgery. Moreover, during the next 12 h, there were significant differences observed in the level of pain between both groups. There was also considerable difference between both groups in the time of first analgesic intake and the total amount of analgesic. Our results show that modified local anaesthesia may be of benefit for the relief of operative and post-operative pain and may also help reduce analgesic intake after oral surgery.

Gingivostomatitis.

Gingivostomatitis (GS) with various patterns of disease may require antiviral therapy, steroids, laser fulguration, immunomodulation drugs, or nonsteroidal anti-inflammatory drugs. The use of cyclosporine as an immunomodulation drug has long-term benefits in reduction of the immunologic events that contribute to GS. Whole-mouth extraction or partial extraction (premolars and molars), with radiographic conformation that all root remnants have been removed, may be the most viable option in nonresponsive and or intractably painful stomatitis in noncompliant cats or dogs. Oral inflammation subsided after extraction without the need for further medication in approximately 70% of the cats from two studies with previous chronic unrelenting oral disease. The combination of immunomodulation with cyclosporine together with laser resection of proliferative tissue should be recommended if extraction of teeth is not desired. Removal of proliferative oral tissues by lasing (carbon dioxide laser) removes the tissue that maybe producing tissue antigens and the area where bacteria are sequestered. The use of anti-inflammatory medications is recommended in the management of GS. Therapeutic success is achieved when there is elimination of proliferative tissue and inflammation.

Lymphoplasmacytic gingivitis in a cat.

A 12-year-old male neutered short haired cat was presented due to difficulty eating and pawing at the face. Examination revealed severe gingivitis and stomatitis throughout the oral cavity. Gingival biopsy provided a diagnosis of lymphoplasmacytic stomatitis. Extraction of all premolars and molars resulted in elimination of all clinical signs.

Microbes of the tonsils in PFAPA (Periodic Fever, Aphtous stomatitis, Pharyngitis and Adenitis) syndrome - a possible trigger of febrile episodes.

Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis (PFAPA) is a childhood febrile syndrome that is often cured by tonsillectomy (TE). We hypothesized that microbes present in the tonsils may act as a trigger for the activation of inflammasomes and investigated the microbiology of the tonsils in PFAPA patients and controls. We recruited 31 consecutive children who underwent TE due to PFAPA; 24 children who underwent TE due to other reasons served as controls. We cultured all the samples for bacteria, mycobacteria, yeasts, and viruses and used PCR for 15 viruses. Also biofilm formation and histologic findings were identified. The samples of the patients yielded Candida albicans more often than did the controls (16 vs 0%, p = 0.003). Staphylococcus aureus occurred in only 10% of the patients, but in 38% of the controls (p = 0.01). Varicella zoster and Herpes simplex viruses occurred less often in patients than in controls. Biofilm was present in 55% of PFAPA tonsils, but in only 24% of the controls (p = 0.03). The microbes found in the tonsils of PFAPA patients showed significant differences from those of controls. This may in part explain the efficacy of TE in PFAPA.

A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication.

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue.

Preprosthetic surgery.

Several of the abnormal conditions existing in the edentulous patient can be corrected surgically, prior to construction of dentures, to enable the patient to function more successfully following prosthetic restoration. The more common problems have been discussed which often require surgical correction. In some instances, articulated diagnostic models of the patient's mouth show that surgery can be avoided, or when surgery is necessary, these models help identify the exact locations of the tissue to be corrected. Alveolectomy has been presented with an eye toward conservatism since this procedure affects the quality of denture foundation and therefore denture stability. Alveolectomy should be performed only when there is a definite indication for the procedure. Correction of soft tissue abnormalities can substantially improve the patient's ability to function with dentures and solve many of the adjustment problems which confront the dentist. It is often better to correct the soft tissue abnormality rather than to circumvent the problem with an inferior prosthetic restoration. Since the introduction of resilient acrylics and tissue conditioning materials, the patient need no longer suffer the discomfort of denture withdrawal after surgery. Electrosurgery has emerged as a successful method of correcting many soft tissue abnormalities. Vestibuloplasty is receiving much emphasis as a possible treatment for atrophic ridges in which there is still enough alveolar bone from which to extend a sulcus. These sulcus extension procedures may offer some help in the future regarding the problem of resorbed ridges, but presently, more research is necessary before widespread use is recommended.