Could MRONJ Be Related to Osimertinib Monotherapy in Lung Cancer Patients after Denosumab Suspension?

BACKGROUND: Medication-related osteonecrosis of the jaws is the most frequent complication in patients treated or in therapy with antiresorptive/antiangiogenetic drugs. The list of medications possibly related to MRONJ onset is constantly growing; we aimed to report on a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (Osimertinib) as possibly responsible for bilateral maxillary necrosis onset in the herein-described case. METHODS: In June 2023, an oncologic patient with two different maxillary bone exposures was referred to our attention. His medical history revealed a two-year Denosumab regimen along with Osimertinib, the latter not suspended before teeth extractions. The clinicians performed a sequestrum removal and bone debridement after three cycles of antibiotic therapy. RESULTS: Histologic examinations confirmed the clinical diagnosis of MRONJ excluding a metastatic occurrence, while complete mucosal healing was achieved after 15 days. CONCLUSIONS: The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes.

Type 1 citrullinemia patient with Brugada pattern undergoing general anesthesia for dental extractions: A case report.

Key Clinical Message: The perioperative control of ammonia, reduction of stress, and administration of drugs tolerated in type 1 citrullinemia and Brugada pattern allowed the successful and uneventful management of general anesthesia in the study patient. Abstract: The aim of this study was to report the targeted perioperative management of general anesthesia (GA) adopted for dental extractions in a rare patient with type 1 citrullinemia and Brugada pattern. A male, Caucasian, adult type 1 citrullinemia patient needed dental extractions under GA. The medical history showed neurodevelopmental impairment, growth retardation, epilepsy, and a Type 2 Brugada electrocardiographic pattern in the second precordial lead. The authors focused the anesthesiologic protocol on the prevention of hyperammonemia and fatal arrhythmias. Changes in diet and 10% glucose solution administration prevented protein catabolism due to the fasting period (ammonia was 44 µmol/L preoperatively and 46 µmol/L postoperatively; glycemia was 120 g/dL preoperatively and 153 g/dL postoperatively). The patient received a continuous electrocardiogram, noninvasive blood pressure, pulse oximeter, entropy monitoring, train-of-four monitoring, and external biphasic defibrillator pads. Midazolam, remifentanil, and dexamethasone were administered for pre-anesthesia; thiopental and rocuronium for induction; remifentanil and desflurane for maintenance; sugammadex for decurarization. After the intraligamentary injection of lidocaine 2% with epinephrine 1:100,000 for local anesthesia, the patient developed a transient Type 1 Brugada pattern that lasted a few minutes. The whole procedure lasted 30 min. The patient's discharge to ward occurred 3 h after the end of GA. The perioperative management of ammonia, reduction of stress, and administration of drugs tolerated in Type 1 citrullinemia and Brugada pattern allowed the successful and uneventful administration of GA in the study patient.

The Effect of a Zinc-L-Carnosine Mouthwash in the Management of Oral Surgical Wounds: Preliminary Results of a Prospective Cohort Study.

BACKGROUND: Zinc L-carnosine promotes the transition from the inflammatory to the proliferative phase of wound healing by reducing the expression of pro-inflammatory signals and enhancing the expression of anti-inflammatory signals. This prospective cohort study aims to test the effect of a zinc-L-carnosine mouthwash in promoting oral surgical wound healing. METHODS: From October 2022 to February 2023, the authors enrolled healthy adult volunteers who needed the extraction of bilateral molars at the Unit of Dentistry of the University of Bari. The authors studied the baseline wound healing of each patient after the first extraction. Three months later, the patients underwent the second extraction and rinsed their mouths with zinc-L-carnosine mouthwash twice per day for the following 28 postoperative days. For a month after each extraction, the patients received weekly follow-up visits by an oral surgeon blinded about the study to record the modified healing index score of the wounds (range 0-6 points). For statistical analysis, we used the one-tailed t-test for paired samples with a significance level set at p < 0.05 to compare the baseline scores with those recorded during the exposure to the zinc-L-carnosine mouthwash. RESULTS: The authors enrolled four women and six men (mean age = 44.60 ± 19.22 years). On the seventh and fourteenth postoperative days, the mean difference between the modified healing index scores obtained by using the zinc-L-carnosine mouthwash and the baseline was not significant. On the twenty-first postoperative day, the mean score obtained by using the mouthwash was 5.2 ± 1.3 points and was significantly higher than the 4.7 ± 1.8 points of the baseline (p = 0.026). On the twenty-eighth postoperative day, the mean difference was significant as well (5.9 ± 0.3 points and 5.4 ± 1.1 points, respectively). CONCLUSION: The preliminary results of this study showed that the zinc-L-carnosine mouthwash improved the quality of oral surgical wound healing.

Targeted Diode Laser Therapy for Oral and Perioral Capillary-Venous Malformation in Pediatric Patients: A Prospective Study.

BACKGROUND: This study describes the management protocol for capillary-venous malformations in pediatric patients and reports the epidemiology of diagnosed and treated cases at the Unit of Odontostomatology of the Aldo Moro University of Bari from 2014 to 2022. METHODS: The authors classified the intraoral and perioral capillary-venous malformations by superficial diameter (<1 cm, 1-3 cm, >3 cm) and ultrasonographical depth extension (≤5 mm, >5 mm). All patients underwent pulsed-mode diode laser transmucosal photocoagulation (8-12 W/cm2); those with malformations that were wide (>3 cm) and deep (>5 mm) received intralesional photocoagulation, too (13 W/cm2). The children received general anesthesia based on their compliance and lesions' extension. The follow-up lasted six months. RESULTS: A total of 22 females and 14 males (age range 4-18 years) presented 63 capillary-venous malformations. Five patients with Sturge-Weber syndrome, seven with hereditary hemorrhagic telangiectasia, and five with angiomatosis showed multiple malformations. The authors found no intraoperative or postoperative complications. Seventeen patients with lesions >1 cm and >5 mm deep required multiple laser sessions to heal. CONCLUSION: The results of the current study support diode laser photocoagulation as the gold standard for the treatment of intraoral and perioral capillary-venous malformations in pediatric patients.

Effect of Preoperative Music Therapy Versus Intravenous Midazolam on Anxiety, Sedation and Stress in Stomatology Surgery: A Randomized Controlled Study.

BACKGROUND: Patients undergoing surgery and general anesthesia often experience anxiety, fear and stress, with negative bodily responses. These may be managed by the pre-procedural application of anxiolytic, analgesic, and anesthetic drugs that have, however, potential risks or side effects. Music therapy (MT) can be used as a complementary no-drug intervention alongside standard surgical care before, during and after medical procedures. The aim of this study was to evaluate the effects of preoperative MT intervention compared to premedication with midazolam on levels of anxiety, sedation and stress during general anesthesia for elective stomatology surgery. METHODS: A two-arm randomized and controlled single-center, parallel-group, pre-post event study was conducted. In total, 70 patients affected by stage I or II (both clinically and instrumentally N0) micro-invasive oral cancer and undergoing elective surgery under general anesthesia were assigned to the control group (CG) or to the music therapy group (MTG). MTG patients received preoperative music therapy intervention (MT) from a certified music therapist before surgery, while the CG patients did not receive MT but instead received premedication with intravenous midazolam, 0.02 mg/kg. Anesthesia was the same in both groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at the entrance to the operating room, just before the induction of anesthesia and every 5 min until the end of surgery. An anxiety visual analogues scale (A-VAS) was used to evaluate the level of anxiety. The bispectral index (BIS) monitor was used to measure the depth of sedation just before and 10 min after both music intervention and midazolam administration. Stress response was assessed 5 min before and 20 min after surgery via the control of plasma prolactin (PRL), growth hormone (GH), and cortisol levels. The patient global impression of satisfaction (PGIS) was tested 1 h after surgery. Participants in the MTG were asked to answer 3 questions concerning their experience with MT. RESULTS: No statistical differences among the PRL, GH and cortisol levels between the two groups were registered before and after the treatment, as well as for PAS, PAD and HR. Significant differences in the A-VAS scores between the MTG and CG (p < 0.01) was observed. Compared to the CG, MTG patients had a statistically significantly lower BIS score (p = 0.02) before induction. A PGIS score of 86.7% revealed that patients in the MTG were very satisfied, versus 80% in the CG (p < 0.05). CONCLUSION: Preoperative music therapy could be an alternative to intravenous midazolam when aiming to promote a preoperative and post-operative state of anxiolysis and sedation in stomatology surgery, even if no differences were found in terms of the surgery-related stress response according to physiological and hormonal determinations.

Oral lichen planus in children: An Italian case series.

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.

Oral lesions with immunohistochemical evidence of Sars-CoV-2 in swab-negative post-COVID syndrome.

OBJECTIVES: Growing evidence exists about post-COVID condition/syndrome as sequelae of Sars-CoV-2 infection in healed patients, possibly involving the lungs, brain, kidney, cardiovascular and neuromuscular system, as well the persistency of taste dysfunction. Such symptoms develop during or after infection and continue for more than 12 weeks with pathogenesis related to virus persistency but variable by organs or systems. MATERIALS AND METHODS: We recently observed six patients recovered from COVID-19 and with negative RT-PCR testing, showing oral mucosa lesions (mainly ulcers) overlapping those occurring in the acute phase, persisting up to 20 days and thus needing a biopsy with histological investigation and spike protein evaluation by immunohistochemistry. RESULTS: We found epithelial ulceration, inflammatory infiltrate, vessels with increased diameter and flattened endothelium but no thrombi formation; also, we found a weak epithelial SARS-CoV-2 positivity limited to the basal/spinosum layers, progressively decreasing toward the periphery, and the intraepithelial lymphomonocytes, endothelium, and perivascular pericytes too. CONCLUSIONS: Our findings provide evidence that SARS-CoV-2 can persist, as for other organs/systems, also in the oral epithelium/mucosa after the acute phase and can be responsible for lesions, although by a pathogenetic mechanism that should be better defined but certainly referable as the oral mucosa counterpart of post-COVID syndrome.

Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review.

Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.

Relationship between oral lesions and severe SARS-CoV-2 infection in intensive care unit patients.

OBJECTIVE: Oral lesions received increased attention as likely new signs or secondary manifestations of COVID-19. Therefore, we clinically examined oral cavity of patients with COVID-19 and investigated oral lesions and patient comorbidities as possible risk factors of COVID-19 disease outcome. METHODS: From January to March 2022, a prospective study was conducted by recruiting all COVID-19 patients admitted to the Intensive Care Unit and Respiratory Intensive Care Unit of Maxi-Emergencies Hospital in Bari, Italy. RESULTS: From the enrolled 103 COVID-19 patients, 46.6% were females and 53.4% were males. Findings show that risk of presenting with severe COVID-19 disease was higher in patients who developed oral lesions related to COVID-19 than those with no oral lesions (RR = 7.998, p = .002). Next, patients with concomitant autoimmune diseases were at higher risk of a negative COVID-19 disease outcome than those without comorbidities (OR = 8.838, p = .026). CONCLUSIONS: COVID-19-related lesions of oral mucosa should not be ignored as they can be early and easily detectable signs of severe COVID-19 disease condition, thus, serving as a prevention measure for any potential unfortunate event. Findings of this study, without implying causation, offer a direction for future investigations that aim to confirm the presence of specific oral lesions in COVID-19 patients as signs of severe disease progression.

Medication-related osteonecrosis of the jaw triggered by endodontic failure in oncologic patients.

OBJECTIVES: To describe the association between endodontic treatment failure and medication-related osteonecrosis of the jaw (MRONJ) in a cohort of oncologic patients in therapy with antiresorptive and antiangiogenic drugs. MATERIALS AND METHODS: Patients were selected as affected by MRONJ in absence of the common local risk factors (oral surgical procedures or ill-fitting dentures) but showing failure of previous endodontic treatment performed at least 6 months before the starting of antiresorptive/antiangiogenic therapies. Jaw lesions were all surgically treated and patients underwent a strict clinical and radiological follow-up. RESULTS: Among 18 patients, who developed 18 MRONJ, the only detectable local risk factor was the presence of teeth with failed endodontic treatment (more precisely, root canal underfilling in eight cases, root canal overfilling in two cases, root perforation in three cases, root fracture in five cases). All patients completely healed after surgical procedure and no recurrence was observed. CONCLUSIONS: Endodontic treatment failure should be considered a local risk factor for MRONJ development in oncologic patients. For such reason, it is mandatory to carefully evaluate them prior than the beginning of antiresorptive and antiangiogenic drugs administration.

Lingual laser frenotomy in newborns with ankyloglossia: a prospective cohort study.

BACKGROUND: The study aims to describe the lingual laser frenotomy perioperative protocol for newborns with ankyloglossia with or without breastfeeding difficulties developed by Odontostomatology and Neonatology and Neonatal Intensive Care Units of the Aldo Moro University of Bari. METHODS: Authors carried out a prospective observational cohort study. Newborns with ankyloglossia (classified by using both Coryllos' and Hazelbaker's criteria) with or without difficult breastfeeding (according to Infant Breastfeeding Assessment Tool) underwent diode laser frenotomy (800 ± 10 nm; 5 W; continuous wave mode; contact technique; under topical anesthesia) and follow-up visits after seven and thirty days postoperatively. The authors analyzed as main outcomes the perioperative pain intensity measured by the C.R.I.E.S. scale, the occurrence of complications and quality of healing, the quality of breastfeeding, newborn's postoperative weight gain, maternal nipple pain, and the presence of lesions as secondary outcomes. RESULTS: Fifty-six newborns were included in the current study. Intraoperative mean pain intensity was 5.7 ± 0.5 points, resolved within thirty postoperative minutes. Observed complications were mild punctuating bleeding, carbonization of the irradiated site, and transitory restlessness. All wounds were completely healed within the thirtieth postoperative day. During follow-up, a significant breastfeeding improvement was evident with satisfactory newborns' weight gain and a significant reduction of nipple pain and lesions (p < .05). CONCLUSION: Our lingual laser frenotomy protocol provided significant breastfeeding improvement in the mother-newborn dyads with low intraoperative pain and no significant complications.

Cavernous Sinus Involvement and Near Miss Mediastinitis following Mandibular Tooth Infection Treated during the COVID-19 Pandemic: Clinical Diagnosis and Treatment.

Odontogenic infections represent a frequent condition that in some cases, if not treated promptly, can spread quickly to the rest of the body and turn into life-threatening infections. In this work, the case is reported of a 59-year-old woman, diabetic and overweight, who presented to the Odontostomatology and Otolaryngology Section of the Policlinic of Bari with mandibular tooth infection that had developed into a deep neck space infection leading to the involvement of cavernous sinuses and near mediastinum. The diagnosis, the surgical drainage of the phlegmon and removal of infection foci, appropriate control of the airways, and a correct antibiotic therapy made it possible to avoid a potentially fatal condition. Prompt management and early diagnosis of deep space neck infections, such as phlegmon and/or necrotizing fasciitis, with the auxilium of CT scans and tools such as LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), NLR (Neutrophil-to-Lymphocyte Ratio), and LRINECxNLR scores (Laboratory Risk Indicator for Necrotizing Fasciitis and Neutrophil to Lymphocyte Ratio), are advised to evade delays and complications that could potentially worsen the patient's outcome.

Peri-Implant Metastasis as First Manifestation of an Unknown Lung Cancer: Literature Review and Two New Cases.

Metastases around dental implants are extremely rare. They usually represent a secondary localization of a multiorgan metastatic neoplasm but also are, exceptionally, recognized as the first clinical manifestation of a still unknown cancer of whatever organ. Metastases usually manifest as rapidly growing lesions of hard and soft tissues and always represent a true diagnostic/therapeutic dilemma both for clinicians in choosing the more appropriate treatment and for pathologists in recognizing the primary tumor when still undiagnosed. We report 2 distinct cases of metastasis occurring around dental implants in the maxilla and mimicking peri-implantitis at the onset; more precisely, in one case, the lesion involved exclusively the alveolar bone, where an implant were previously inserted, while in the other case, a neoplasm caused bone destruction around the fixture with an impressive and rapid exophytic growth. In both cases, maxillary lesions were the first metastatic manifestation of an unknown adenocarcinoma of the lung.

Peri-implantitis-like medication-related osteonecrosis of the jaw: Clinical considerations and histological evaluation with confocal laser scanning microscope.

OBJECTIVE: In the recent years, an increasing number of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) have been reported in literature, both in oncologic and osteoporotic patients. The aim of this study is to describe 19 cases of patients previously diagnosed as affected by peri-implantitis, who were treated for PI-MRONJ, with consideration on clinical and histopathological features. MATERIALS AND METHODS: Patients included were affected by postmenopausal osteoporosis and were administered with different antiresorptive drugs. Due to the presence of clinical and radiological signs of peri-implantitis not healed after non-surgical periodontal treatment, they were referred to the Complex Operating Unit of Odontostomatology of the University of Bari. Then, after a drug holiday of at least 3 months and cycles of antibiotics, and after other cycles of periodontal treatment, patients underwent the surgical removal of implant fixtures and surrounding bone. RESULTS: Although the previous diagnosis of peri-implantitis, the histopathological analysis with both conventional and confocal laser scanner microscopy confirmed the diagnosis of peri-implantitis-like MRONJ. CONCLUSION: Peri-implantitis not healed after conventional treatment in patients at risk on MRONJ occurrence should be considered as peri-implantitis-like PI-MRONJ and treated as required in order to get complete healing of the pathological condition, thus avoiding delay in the diagnosis.

Cocaine-Induced Midline Destructive Lesions (CIMDL): A Real Challenge in Diagnosis.

The prolonged use of intranasal cocaine can destroy the nasal architecture with the erosion of the palate, turbinates, and ethmoid sinuses causing cocaine-induced midline lesions (CIMDL). The CIMDL display a clinical pattern mimicking variable diseases. The aim of this study was to highlight the difficulties in reaching a correct diagnosis through the evaluation of eight new cases. The diagnostic procedures followed in these patients included: detailed medical history, clinical and histological examination, computed tomography and magnetic resonance imaging, laboratory findings (complete blood count, sedimentation rate, antinuclear antibody test, rheumatoid factor, venereal disease research laboratory test, leishmaniasis and fungal serology, antineutrophil cytoplasmic antibodies ANCA test), and chest X-ray. All patients complained of epistaxis, halitosis, nasal scabs and obstruction, decreased sense of smell and/or taste, oro-nasal regurgitation of solids and liquids with recurrent sinus infections, and chronic facial pain. On clinical examination, all patients showed palate perforation with variable nasal structure involvement and presented a strong positivity for ANCA tests with a p-ANCA pattern. The followed protocol for the CIMDL diagnosis allowed for a relatively quick and conclusive diagnosis in all patients. A multidisciplinary approach is mandatory in the management of CIMDL, involving dental professionals, maxillofacial surgeons, and psychologists.

Effectiveness of Dental and Maxillary Transverse Changes in Tooth-Borne, Bone-Borne, and Hybrid Palatal Expansion through Cone-Beam Tomography: A Systematic Review of the Literature.

Background and Objectives: Palatal expansion is a common orthodontic technique able to increase the transverse changes for subjects with constricted maxillary arches. The aim of the present investigation was to evaluate through a systematic review the tomography effectiveness of different palatal expander approaches. Materials and Methods: The database used to perform the screening and determine the eligibility of the clinical papers was PubMed (Medline). Results: The database search included a total of 284 results, while 271 articles were excluded. A total of 14 articles were included for the qualitative assessment. Conclusions: The effectiveness of the present studies reported that skeletal expansion was a useful approach to increase the transverse changes for subjects with constricted maxillary arches.

Oral and Maxillo-Facial Manifestations of Systemic Diseases: An Overview.

Many systemic (infective, genetic, autoimmune, neoplastic) diseases may involve the oral cavity and, more generally, the soft and hard tissues of the head and neck as primary or secondary localization. Primary onset in the oral cavity of both pediatric and adult diseases usually represents a true challenge for clinicians; their precocious detection is often difficult and requires a wide knowledge but surely results in the early diagnosis and therapy onset with an overall better prognosis and clinical outcomes. In the current paper, as for the topic of the current Special Issue, the authors present an overview on the most frequent clinical manifestations at the oral and maxillo-facial district of systemic disease.

Covid-19 Symptomatic Patients with Oral Lesions: Clinical and Histopathological Study on 123 Cases of the University Hospital Policlinic of Bari with a Purpose of a New Classification.

The aim of this study is to report on the oral lesions detected in 123 patients diagnosed at the University Hospital of Bari from October 2020 to December 2020, focusing on the correlation of clinical and pathological features in order to purpose a new classification. METHODS: General and specialistic anamnesis were achieved and oral examination was performed. The following data were collected: age/gender, general symptoms and form of Covid-19, presence and features of taste disorders, day of appearance of the oral lesions, type and features of oral lesions and day of beginning of therapies. If ulcerative lesions did not heal, biopsy was performed. RESULTS: Many types of oral lesions were found and classified into four groups considering the timing of appearance and the start of the therapies. Early lesions in the initial stages of Covid-19 before the start of therapies was observed in 65.9% of the patients. In the histopathological analysis of four early lesions, thrombosis of small and middle size vessels was always noticed with necrosis of superficial tissues. CONCLUSION: The presence of oral lesions in early stages of Covid-19 could represent an initial sign of peripheral thrombosis, a warning sign of possible evolution to severe illness. This suggests that anticoagulant therapies should start as soon as possible.