Brazilian dental consensus on dental management in hematopoietic stem cell transplantation−Part I−pre-HSCT

ABSTRACT The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that On behalf of the Dental Committee of the Brazilian Society of Gene Therapy and Bone Marrow Transplantation (SBTMO) can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Brazilian dental consensus on dental management in hematopoietic stem cell transplantation - Part I - pre-HSCT.

The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Magnetic resonance imaging evaluation of the disc morphology of temporomandibular joint in patients with severe hemophilia.

OBJECTIVES: This study aimed to assess the morphological differences in the articular disc (AD) between hemophilic patients and healthy individuals of the control group for further association with signs and symptoms. METHODS: Fourteen severe hemophilic patients had their AD evaluated by magnetic resonance imaging (MRI). The morphological findings were compared to those of a control group consisting of 14 healthy individuals. MRI was used to evaluate all the components of the temporomandibular (TMJ), including the AD, resulting in sequential T1-weighted parasagittal images. All the images were acquired with teeth in maximum intercuspation position. RESULTS: Morphological alterations showed significant statistical differences (P-value = 0.0068), whereas no statistical differences were found in the other variables, including TMJ pain, headache, bruxism and mouth opening limitation. In the group of non-hemophilic individuals, only two (14.29%) presented AD with non-biconcave features, whereas in the group of hemophilic patients, nine (64.29%) presented AD with a morphology other than biconcave. CONCLUSIONS: In patients with severe hemophilia, there seems to be a pattern of morphological alterations in the articular disc over time. The standard biconcave morphology of AD tends to change into other ones, particularly biplanar, hemiconvex and folded.

Salivary BPIFA proteins are altered in patients undergoing hematopoietic cell transplantation.

OBJECTIVE: The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients. MATERIAL AND METHODS: This longitudinal study included patients who had undergone autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), and unstimulated saliva was collected at three time points, with a fourth collection at oral chronic graft-versus-host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients. RESULTS: Auto-HCT patients showed increased levels of BPIFA1 (p = .021) and BPIFA2 at D+7 (p = .040), whereas allo-HCT group demonstrated decreased expression of BPIFA2 at D+8 (p = .002) and at D+80 (p = .001) and a significant association between BPIFA2 low levels and hyposalivation was observed (p = .02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (p = .04). CONCLUSIONS: The results of this study show distinct pattern of expression of BPIF proteins in both auto-HCT and allo-HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease.

The allogeneic hematopoietic stem cell transplantation procedure-the only curative therapy for many types of hematological cancers-is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day -10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD.

A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions.

PURPOSE: To review the literature for outcome measures for oral viral infections in cancer patients. A secondary aim was to update the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of oral viral infections in cancer patients. METHODS: Databases were searched for articles published in the English language, 1981-2013. Studies that met the eligibility criteria were reviewed systematically. The data about the outcome measures were classified according to the aim of the study: prevention, treatment, or non-interventional. The results of interventional studies were compared to the 2010 MASCC/ISOO publication. RESULTS: Multiple clinical and laboratory tests were used to measure oral viral infections, with great variability between studies. Most of the studies were about Herpes Simplex Virus (HSV). The outcome measure that was most commonly used was the presence of HSV infection diagnosed based on a combination of suggestive clinical presentation with a positive laboratory result. HSV culture was the most commonly reported laboratory outcome measure. Acyclovir and valacyclovir were consistently reported to be efficacious in the management of oral herpetic infections. No new data on the quality of life and economic aspects was found. CONCLUSIONS: Considering the variability in outcome measures reported to assess oral herpetic infections the researcher should select carefully the appropriate measures based on the objective of the study. Acyclovir and valacyclovir are effective in the management of oral herpetic infections in patients receiving treatment for cancer. Studies on newer anti-viral drugs may be useful to address the issue of anti-viral resistance.

Foreign Body in Jugal Mucosa

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.(AU)

Foreign Body in Jugal Mucosa.

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2 months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries.

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

Diversas doenças sistêmicas e seus tratamentos podem predispor ao desenvolvimento de cáries dentárias agressivas. A radioterapia de cabeça e pescoço, quimioterapia, síndrome de Sjögren e tratamentos prolongados com as drogas que induzem a hipossalivação são algumas destas condições. O objetivo deste artigo é descrever as características clínicas de cinco pacientes que desenvolveram doença do enxerto contra hospedeiro crônica (DECHc) como uma complicação do transplante alogênico de células-tronco hematopoiéticas (aloTCTH) e, apesar do acompanhamento periódico com dentistas, desenvolveram cáries rampantes. Nestes casos relatados, as restaurações mostraram falhas precoces e as cáries continuaram progredindo até a destruição generalizada dos dentes. A maioria dos dentes, portanto, foi extraída devido à cárie avançada e rápida progressão clínica. Neste artigo, o termo "cáries relacionadas à DECHc" é proposto para descrever esta complicação pouco conhecida do tratamento do câncer, que se manifesta em receptores de TCTH que desenvolvem DECHc. Esta condição é pouco reconhecida na literatura e pode representar o resultado final do agrupamento das complicações bucais em pacientes com DECHc, incluindo mucosite, dor oral, hipossalivação, perda de paladar e infecções orais, levando à cárie rampante devido à dificuldade de higiene oral e aumento da ingestão de alimentos altamente cariogênicos. Por consequência, o conhecimento desta complicação oral deve melhorar os tratamentos médico e odontológico das manifestações bucais da DECHc e melhorar a qualidade de vida dos pacientes com esta complicação após o TCTH.

Tooth alterations in areas of bisphosphonate-induced osteonecrosis.

OBJECTIVE: Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis. MATERIALS AND METHODS: Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-µm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope. RESULTS: The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %). CONCLUSIONS: Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications. CLINICAL RELEVANCE: It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

Randomized double-blind clinical trial comparing clobetasol and dexamethasone for the topical treatment of symptomatic oral chronic graft-versus-host disease.

Patients who undergo allogeneic stem cell transplantation frequently develop an immunologic disease caused by the reactivation of the graft to the host tissues. This disease is called graft-versus-host disease (GVHD) and it is usually a systemic disorder. In a large proportion of cases, oral disorders that are related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves the use of topical immunosuppressive drugs. Several medications have been studied for this purpose, but only a small number of clinical trials have been published. The present study is a randomized, double-blind clinical trial that compares topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD. Patients were randomly assigned to treatment with clobetasol propionate .05% or dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was administered with the corticosteroid. Oral lesions were evaluated by the modified oral mucositis rating scale (mOMRS) and symptoms were registered using a visual analogue scale. Thirty-five patients were recruited, and 32 patients were randomized into the study groups: 18 patients (56.3%) to the dexamethasone group and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted in a significant reduction in mOMRS total score (P = .04) and in the score for ulcers (P = .03). In both groups, there was significant symptomatic improvement but the response was significantly greater in the clobetasol group (P = .02). In conclusion, clobetasol was significantly more effective than dexamethasone for the amelioration of symptoms and clinical aspects of oral lesions in cGVHD.

Early and late oral features of chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. OBJECTIVE: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. METHODS: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year). RESULTS: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72%) in the group with less than one year after transplantation, and 34 (77.27%) in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. CONCLUSION: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Early and late oral features of chronic graft-versus-host disease

Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year). Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72%) in the group with less than one year after transplantation, and 34 (77.27%) in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation. .

Atuação multidisciplinar em faringoestomatologia / Multidisciplinary approach in stomatology

Objetivo: Este artigo tem o objetivo de analisar dadosepidemiológicos e clínicos do serviço de faringoestomatologia dadisciplina de otorrinolaringologia, cabeça e pescoço de todos ospacientes atendidos nos primeiros dez meses de funcionamento.Método: Foram atendidos 41 pacientes, a idade média dospacientes atendidos foi de 52 anos (12-80). Resultados: O tempomédio de duração das queixas principais foi de 38 meses. A queixamais frequente foi lesão na cavidade oral, seguida de xerostomiae ardência bucal. Dez (24%) dos 41 pacientes eram tabagistase seis (14%) ex-tabagistas. As patologias mais frequentes foramcandidíase, refluxo faringolaríngeo, má adaptação da prótesedentária, leucoplasias e síndrome da ardência bucal. A presençade serviços de faringoestomatogia em hospitais terciários éessencial para a avaliação, seguimento e tratamento adequado depacientes com patologias específicas da área. Conclusão: Houvediversidade e riqueza de situações clínicas em nosso serviço.Alguns hábitos como o tabagismo, uso e manutenção inadequadosde prótese dentária foram bastante frequentes. A abordagemmultidisciplinar na avaliação e tratamento dos pacientes faz partedo serviço contribuindo para uma melhor formação do residente.

Linear epidermal nevus of the oral cavity: a rare diagnosis.

Linear epidermal nevus is an uncommon diagnosis of benign lesions of the oral cavity. It is characterized by a congenital malformation arising from the ectoderm cells, which are arranged according to a typical linear configuration known as Blaschko's lines. We report a case of linear epidermal nevus of oral cavity in a 51-year-old lady or woman. The linear epidermal nevus of the oral cavity, although rare, can be considered a differential diagnosis of oral papillomatosis (OP). The histopathological studies and detailed description are the center of the diagnostic and clinical evolution.