Oral and cutaneous immune-related adverse events in cancer patients: Prevalence and overall survival.

OBJECTIVES: To assess the prevalence of cutaneous and oral immune-related adverse events (irAEs) in cancer patients, risk factors for its development, and overall survival (OS). MATERIALS AND METHODS: This retrospective observational study which included 748 medical records of cancer patients who received immune checkpoint inhibitors (ICIs). Demographic and clinicopathological characteristics were collected and analyzed. RESULTS: Most patients were male (59.4%), with stage IV cancer (65%) and received pembrolizumab (46.7%). Four hundred fourteen (55.34%) patients developed cutaneous lesions, 84 (11.2%) developed oral mucosal lesions, and 70 (9.3%) developed xerostomia. The median time for irAEs development was 11 weeks for cutaneous and oral mucosal lesions, and 21.5 weeks for xerostomia. Patients who received PD-1 + CTLA-4 had a higher risk for developing cutaneous irAEs (p = 0.001), while those who underwent ICI and concurrent chemotherapy had a higher risk (p = 0.008) for developing oral mucosal lesions. Patients who presented oral and cutaneous irAEs had better OS than those who did not present (p = 0.0001). CONCLUSION: Cutaneous effects affected more than half of the patients, while oral effects and xerostomia were found in around 11% and 9% of patients, respectively. Concurrent chemotherapy and PD-1 + CTLA-4 were more associated with oral and cutaneous irAEs, respectively. Patients who developed such irAEs had better overall survival.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

3D printing technology to produce intraoral stents for head and neck radiotherapy: A scoping review.

INTRODUCTION: Radiotherapy remains one of the main treatments for head and neck cancer; however, it is accompanied by acute and chronic adverse effects. Use of three-dimensional (3D) oral stents to modulate radiation intensity to specific target areas have been developed to minimize these adverse effects. This study aimed to present a scoping review of studies published on 3D printing of oral stents and their clinical applicability. METHODS: MEDLINE/Pubmed, Scopus, Web of Science and CENTRAL Cochrane data bases were searched, studies selected, and data collected by three independent reviewers up to December 2022. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis-Extension for Scoping Reviews (PRISMA-ScR). RESULTS: The search resulted in 404 studies and 5 articles fulfilled the eligibility criteria and were considered for this review. Three-dimensional printed intraoral stents were produced for 56 patients with indication for radiotherapy. 3D-printed stents were well-tolerated by all tested patients and demonstrated great reproducibility of maxillomandibular relation, required less time for production and lower cost to manufacture. Two studies showed great protection of healthy tissues with 3D-printed stents during radiotherapy. CONCLUSIONS: Three-dimensional printing is promising for production of intraoral stents, however, more studies are needed to improve the technique and further investigate the safety and prevention of oral toxicities from radiotherapy.

Gingival cyst of the adult.

The gingival cyst of the adult (GCA) is a rare odontogenic cyst, consisting of 0.3% of all odontogenic cysts. This case report, based on CARE guidelines for case reports, aims to present a case of a 52-year-old female patient with a symptomatic translucent nodule in the upper left anterior gingiva, measuring approximately 6mm. Excisional biopsy was performed, and the histological examination revealed multiple cystic cavities lined by the squamous epithelium of varying thickness with focal areas of nodular thickenings. The presence of clusters of cells with clear cytoplasm within epithelial thickenings was observed. PAS staining was negative in clear cells. The diagnosis of the GCA was established. Despite its rarity, GCA should be considered in the differential diagnosis of gingival lesions. Conservative surgical treatment proved to be effective, with no signs of recurrence.

Clinicopathological Features of Metastasis to the Oral and Maxillofacial Region-Multicenter Study.

BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

Craniofacial fibrous dysplasia with cystic degeneration - A diagnostic challenge.

Benign fibro-osseous lesions with cystic degenerations have been scarcely reported in craniofacial bones and its unusual characteristics pose a diagnostic challenge. Here, we report a case of craniofacial fibrous dysplasia presenting a large cystic degeneration. A 55-year-old woman had a history of pain, slight asymmetry on the zygomatic region and ocular pressure. Computed tomography revealed on the right side, multiple craniofacial bones showing a ground glass aspect, associated with an extensive hypodense, unilocular, well circumscribed lesion in the maxilla, and smaller lesions in the sphenoid bone. After a surgical procedure performed in another service, there was a complete improvement in symptoms, and after 1 year, the patient remains stable, with no changes. In the literature review, thirty-three reported cases of the same association in the craniofacial region were found. The main symptoms were sudden increase in the lesion and pain, and the indication of intervention in cystic lesions was only indicated in symptomatic cases or functional deficit. The knowledge of the possibility of the association of benign fibro-osseous lesions and cystic degenerations in craniofacial bones is essential to perform a correct diagnosis and treatment for these patients, consequently avoiding unnecessary procedures. Key words:Craniofacial fibrous dysplasia, Fibrous dysplasia, Benign fibro-osseous lesions, Cystic degeneration.

Osteoradionecrosis treatment in head and neck cancer patients: An overview of systematic reviews.

AIMS: Evaluate the existing evidence of osteoradionecrosis (ORN) treatment in adults with head and neck cancer, the methodological quality and the evidence grade within systematic reviews (SRs). METHODS: An extensive systematic literature search of SRs that addressed ORN in head and neck cancer patients was conducted with screening of eligible studies, data extraction, methodological (AMSTAR 2) and evidence quality assessment (GRADE) of the SRs by independent and calibrated authors. RESULTS: A total of six SRs were enrolled. Based primarily on studies from the 1990s, there is critically low- or moderate-quality evidence that hyperbaric oxygen therapy (HBO) improves ORN healing. From 2005 onward, evidence has been discovered in relation to treatment with pentoxifylline and tocopherol (PENTO). The SRs indicate that the management of ORN with PENTO appears to be promising. The greatest rates of healing are seen in mild and moderate stages of ORN. However, the quality of evidence regarding PENTO, surgery and other treatments remains critically low. CONCLUSION: There is no standardized protocol to treat ORN. PENTO appears to be the most promising conservative treatment; however, the current level of evidence regarding PENTO is still critically low. More robust clinical studies are needed to establish the best treatment for ORN.

Gingival cyst of the adult

ABSTRACT The gingival cyst of the adult (GCA) is a rare odontogenic cyst, consisting of 0.3% of all odontogenic cysts. This case report, based on CARE guidelines for case reports, aims to present a case of a 52-year-old female patient with a symptomatic translucent nodule in the upper left anterior gingiva, measuring approximately 6mm. Excisional biopsy was performed, and the histological examination revealed multiple cystic cavities lined by the squamous epithelium of varying thickness with focal areas of nodular thickenings. The presence of clusters of cells with clear cytoplasm within epithelial thickenings was observed. PAS staining was negative in clear cells. The diagnosis of the GCA was established. Despite its rarity, GCA should be considered in the differential diagnosis of gingival lesions. Conservative surgical treatment proved to be effective, with no signs of recurrence.

Solitary fibrous tumor of the tongue.

Solitary fibrous tumor (SFT) is a benign mesenchymal neoplasm originally described in pleura with a rare presentation in the oral cavity. Herein, we report a case of a 28-year-old male patient who presented an asymptomatic slow-growing mass in the anterior part of the tongue. Intraoral examination revealed a well-circumscribed mass covered by normal mucosa with a fibrous consistency. Due to non-specific clinical findings, the initial diagnostic hypotheses include benign submucosal neoplasms such as leiomyoma, neurofibroma, SFT, and others. An excisional biopsy was performed. Microscopically, the tumor was surrounded by a thick fibrous capsule; hypo and hypercellular areas were arranged in a storiform pattern with a stroma formed by collagen and abundant vascularization. Tumor cells showed immunopositivity for CD34 and STAT-6 and no expression of CD99, AML, S-100, and Ki-67. According to these findings, the diagnosis of SFT was established. After 24 months, the patient is asymptomatic and has no evidence of recurrence. Although oral involvement is rare, SFT should be included in the differential diagnosis of oral submucosal lesions.

Secondary primary tumor mimicking osteoradionecrosis.

Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long-term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.

Bethanechol used to prevent salivary gland dysfunction in patients submitted to radioactive iodine therapy: A double blind, placebo-controlled, randomized study.

Symptoms related to salivary gland damage are one of the most frustrating complications after radioactive iodine (131I) therapy. To the best of our knowledge, this is the first study that aimed to evaluate the prophylactic effect of Bethanechol on the radioiodine content of salivary gland. Fifty patients who were referred to 131I therapy were randomized into Bethanechol and placebo groups. Patients received Bethanechol or Placebo (25 mg, 2 times daily), starting 2 h after 131I therapy to 1-month.  Both groups were compared at baseline, 10, 30 and 90 days after 131I therapy based on the following: symptoms related to salivary gland damage; unstimulated whole saliva (UWS) and quality of life using University of Washington Quality of Life 4 questionnaire. Bethanechol group presented significantly lower complaints of dry mouth on 10 (p = 0.047) and 30 (p = 0.003) days compared with placebo. Salivary gland pain and swelling were more frequent among placebo patients at 10 days (p = 0.047). Comparison of the two groups by UWS, no statistical difference was found. Placebo group presented worse score related to activity (p = 0.034), saliva (p = 0.05) and humor (p = 0.05) at 10 days; palate (p = 0.05) and saliva (p = 0.05) at 1 month. Interestingly, Bethanechol patients who received 131I dose > 125mCi, showed better xerostomia indices when compared to the Placebo with same dose. Bethanechol during 131I therapy was found to be effective in decreasing the acute salivary gland damage with impact on patients' quality of life.

Solitary fibrous tumor of the tongue

ABSTRACT Solitary fibrous tumor (SFT) is a benign mesenchymal neoplasm originally described in pleura with a rare presentation in the oral cavity. Herein, we report a case of a 28-year-old male patient who presented an asymptomatic slow-growing mass in the anterior part of the tongue. Intraoral examination revealed a well-circumscribed mass covered by normal mucosa with a fibrous consistency. Due to non-specific clinical findings, the initial diagnostic hypotheses include benign submucosal neoplasms such as leiomyoma, neurofibroma, SFT, and others. An excisional biopsy was performed. Microscopically, the tumor was surrounded by a thick fibrous capsule; hypo and hypercellular areas were arranged in a storiform pattern with a stroma formed by collagen and abundant vascularization. Tumor cells showed immunopositivity for CD34 and STAT-6 and no expression of CD99, AML, S-100, and Ki-67. According to these findings, the diagnosis of SFT was established. After 24 months, the patient is asymptomatic and has no evidence of recurrence. Although oral involvement is rare, SFT should be included in the differential diagnosis of oral submucosal lesions.

Secondary primary tumor mimicking osteoradionecrosis

ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long‐term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.

Intraoral versus extraoral photobiomodulation therapy in the prevention of oral mucositis in HSCT patients: a randomized, single-blind, controlled clinical trial.

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019.

Oral squamous cell carcinoma around dental implants: a systematic review.

OBJECTIVE: This systematic review aimed to evaluate the epidemiologic profile, screen for possible risk factors, and evaluate the spectrum of clinical characteristics of oral squamous cell carcinoma (OSCC) around dental implants (DIs). METHODS: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement. RESULTS: Thirty-three articles met the eligibility criteria. In total, the sample consisted of 63 patients, and women comprised the majority (55.5%). The mean age of patients was 66.7 years. Oral potentially malignant disorders were reported in 46% of patients, of which 65.5% occurred in women. The most common lesion found in women was oral lichen planus (52.6%). In 88.8% of patients OSCC around DIs occurred in the mandible, and the most common clinical appearance of the lesions was an exophytic mass (46%). Most of these lesions were initially treated as peri-implantitis. CONCLUSIONS: Most patients with OSCC around DIs were women without known risk factors. It is important to emphasize that these lesions may present clinical and radiographic features that could resemble peri-implantitis, which can lead to delay in the diagnosis and subsequent treatment.