Prevalence of odontogenic cysts in a group of Libyan population: A retrospective study.

Background: Odontogenic cysts (OCs) are commonly encountered lesions affecting the human jaws having special clinical and radiographic features depending on cyst type. The aim of this study was to determine the prevalence of odontogenic jaw cysts in a Libyan population in Benghazi and to compare these data with previously published reports from Libyan and other geographic areas. Materials and Methods: This is a descriptive study where screening of 2189 biopsies (retrieved from the archives of The Department of Oral Pathology/University of Benghazi, Libya) was performed for the sake of recognizing the three cysts chosen for the purpose of this study. Results: : Out of the screened lesions, 276 cases (12.6%) were diagnosed as odontogenic cysts in the period from 2006 to 2019. Of those, 67.39% were inflammatory and 32.61% were developmental in nature. Radicular cysts (60.5%) were the most frequent cysts followed by dentigerous cysts (14.8%) and keratocysts (14.5%). The mean ages of the patients were 32.3, 29.7, and 33.2 years, respectively. Occurrence of the cysts was noticed more in the maxilla than in the mandible (1.3:1). The overall male-to-female ratio was 1.1:1. Conclusions: The prevalence of odontogenic cysts was similar to that reported in a previous study in Libya and other countries irrespective to WHO (2017) classification of odontogenic cysts.

The American Society of Pediatric Hematology Oncology workforce, productivity, and fellowship assessment: Current state of the workforce.

The American Society of Pediatric Hematology Oncology conducted follow-up workforce surveys in 2017 and 2021 as well as a Pediatric Hematology Oncology Fellowship Program Directors Survey in 2020 to provide an updated review of the current workforce. We provide a comprehensive review and analysis of these results with the goal to provide better understanding of the current landscape in pediatric hematology oncology.

Sentinel lymph node biopsies in early stage oral and oropharyngeal carcinoma: a retrospective single-centre experience.

The aim of this retrospective study was to analyse a consecutive series of patients with oral and oropharyngeal carcinoma who had had sentinel lymph node biopsy (SLNB) at our hospital during 2008-2017. A total of 70 patients with clinically and radiologically confirmed primary oral (n=67) or oropharyngeal (n=3) carcinoma, with no signs of metastatic lymph nodes preoperatively (clinically N0) were included. Patients' clinical and personal data, characteristics of the tumours, sentinel lymph node (SLN) status and outcomes were recorded. Eight patients had invaded SLN. Two patients with clear sentinel lymph node biopsies had recurrences in the cervical lymph nodes with no new primary tumour as origin. The negative predictive value (NPV) and sensitivity for SLNB were 97% and 80%, respectively. The depth of invasion was an individual predictor for cervical lymph node metastasis (p=0.043). Single photo emission computed tomography (SPECT) detected fewer SLN in patients with invaded lymph nodes than in patients with clear lymph nodes (p=0.018). Our data support the use of SLNB as a minimally invasive method for staging the cervical lymph nodes among patients with cN0 oral and oropharyngeal carcinoma. Our results further confirm that greater depth of invasion is associated with cervical lymph node metastases.

Craniomaxillofacial osteosarcoma - The role of surgical margins.

BACKGROUND: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF in Finland to discuss the role of surgery. PATIENTS AND METHODS: All 21 CMF OS patients managed in Finland from 1992 to 2009 were included. The mean age was 40 years (range 15-72). Data on patient and tumor characteristics, treatment modalities, and survival were recorded. All patients had a minimum follow-up of 5 years or until death. RESULTS: OS was evenly represented in the mandible and maxillary bones, which together constituted 76% of all sites. Surgery with curative intent was carried out in 20 patients. Clear margins were achieved in only five cases. Eight (40%) of these 20 patients died due to OS, and their average survival time was 1.3 years. Seven (35%) out of the 20 patients received radiotherapy due to close/intralesional surgical margins, and four of them did not develop recurrences during the follow-up. CONCLUSIONS: The results suggest that postoperative radiotherapy may alter the prognosis in CMF OS, particularly in cases with close or intralesional margins. This may increase the survival rates achieved by prompt action in performing radical surgery.

Similar survival outcome after endoscopic and open approaches for sinonasal mucosal melanoma.

BACKGROUND: To describe a cohort of sinonasal mucosal melanoma (SNMM) patients, and to assess if choice of surgical approach (open versus endoscopic) has impact on survival. METHODOLOGY: Adequate data on clinical presentation, treatment, and recurrence pattern were available for 58 consecutive patients treated for SNMM at the Helsinki University Hospital (HUH) between 1983 and 2016. RESULTS: The 5-year disease-specific survival (DSS) was 27% and overall survival 25% for the whole cohort. The 3-year DSS for patients treated with curative intent with endoscopic surgery was comparable to open surgery (56% and 51%, respectively). Patients with tumours arising from the paranasal sinuses and patients with Stage IV disease had significantly worse prognosis compared with other locations and Stage III patients. All patients who had disease persistence at three months after primary treatment succumbed to SNMM. Post-operative radiotherapy did not affect survival significantly, but a trend towards improved local control was observed. CONCLUSIONS: Local control after endoscopic surgery was comparable to open surgery. Small tumours without local or locoregional spread had improved prognosis, independent of surgical approach. Disease persistence after treatment with curative intent led to death invariably.

Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus.

BACKGROUND: Recent reports have indicated that nonimmune cells can produce low concentrations of histamine. This observation, together with the discovery of the high-affinity histamine H4 receptor (H4 R), has added additional layers of complexity to our understanding of histamine signalling. Human oral keratinocytes (HOKs) possess a uniform H4 R pattern, which is deranged in oral lichen planus (OLP). OBJECTIVES: To investigate histamine metabolism and transport in HOKs of healthy controls and patients with OLP. METHODS: Tissue sections and cultured primary HOKs were studied using immunostaining, quantitative real-time polymerase chain reaction and confocal microscopy. Histamine levels were analysed using high-performance liquid chromatography. RESULTS: l-histidine decarboxylase (HDC) and organic cation transporter (OCT)3 were increased in mRNA and protein levels in patients with OLP compared with controls. In contrast, histamine N-methyltransferase (HNMT) immunoreactivity was decreased in OLP. OCT1/OCT2 and diamine oxidase were not detectable in either tissue sections or in HOKs. Immunolocalization of HDC and OCT3 in HOKs revealed moderate-to-high expression within cytoplasm and cell boundaries. Stimulation with lipopolysaccharide (LPS) or interferon-γ upregulated HDC-gene transcript in HOKs, whereas this was downregulated with high histamine concentration and tumour necrosis factor-α. LPS induced a dose-dependent release of low histamine in HOKs, while high histamine concentration downregulated epithelial adhesion proteins. CONCLUSIONS: HOKs are histamine-producing cells. They release histamine via OCT3 channels in concentrations too low to activate the classical low-affinity H1 R and H2 R, but high enough to stimulate the high-affinity H4 R in autocrine and paracrine modes. The substantially deranged histamine metabolism and transport in OLP could, in part, contribute to the disease pathogenesis.

Pleomorphic adenoma in the nasal cavity: a clinicopathological study of ten cases in Finland.

The objective of the study was to investigate the nationwide occurrence of sinonasal pleomorphic adenoma in Finland. A retrospective study was conducted at The Departments of Otorhinolaryngology-Head and Neck Surgery, and Pathology at the five university hospitals in Finland. Data were obtained by searching for sinonasal pleomorphic adenoma cases in the clinical and histopathological registries at these institutions for the past two to four decades. All patients who had had a histologically proven pleomorphic adenoma in the sinonasal area were included as participants. Ten cases with pleomorphic adenoma of the nasal cavity were found. The majority of these tumours originated in the septum, and there were no malignant transformations. Pleomorphic adenomas of the nasal cavity were found to be extremely rare in this nationwide investigation.

Toll-like receptor 5 and 7 expression in adenoid cystic carcinoma of major salivary glands.

Adenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis and high metastatic rate. Toll-like receptors (TLRs) have been related to tumour progression but have also tumour growth-inhibiting responses. To the best of our knowledge, they have not been studied previously in ACC. We studied the immunoexpression of TLR 5 and 7 in ACC of the major salivary glands. From a cohort of 54 patients with ACC of the major salivary glands treated at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland in 1974-2009, there were 34 primary tumours and six metastases available for immunohistochemical analysis. Immunohistochemical expression of TLR 5 and 7 were correlated to clinicopathological findings and patient survival. Both TLR 5 and 7 were expressed in ACCs and their metastases, mostly on the cell membranes. The expression was heterogeneous in individual tumours. TLR 5 was expressed less in male samples, and TLR 7 had lower expression in ACCs with solid growth pattern. No correlation with survival was found. In the normal salivary gland, the TLR 5 and 7 expression was mainly negative. Both TLR 5 and 7 are expressed in salivary adenoid cystic carcinoma on the cell membranes as well as in cytoplasm.

A simple novel prognostic model for early stage oral tongue cancer.

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1-T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin-eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

Neuropeptide S receptor 1 (NPSR1) activates cancer-related pathways and is widely expressed in neuroendocrine tumors.

Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and express general and specific neuroendocrine markers. Neuropeptide S receptor 1 (NPSR1) is expressed in neuroendocrine cells and its ligand neuropeptide S (NPS) affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used as a biomarker for neuroendocrine neoplasms and to identify the gene pathways affected by NPS/NPSR1. We collected a cohort of NETs comprised of 91 samples from endocrine glands, digestive tract, skin, and lung. Tumor type was validated by immunostaining of chromogranin-A and synaptophysin expression and tumor grade was analyzed by Ki-67 proliferation index. NPS and NPSR1 expression was quantified by immunohistochemistry using polyclonal antibodies against NPS and monoclonal antibodies against the amino-terminus and carboxy-terminus of NPSR1 isoform A (NPSR1-A). The effects of NPS on downstream signaling were studied in a human SH-SY5Y neuroblastoma cell line which overexpresses NPSR1-A and is of neuroendocrine origin. NPSR1 and NPS were expressed in most NET tissues, with the exception of adrenal pheochromocytomas in which NPS/NPSR1 immunoreactivity was very low. Transcriptome analysis of NPSR1-A overexpressing cells revealed that mitogen-activated protein kinase (MAPK) pathways, circadian activity, focal adhesion, transforming growth factor beta, and cytokine-cytokine interactions were the most altered gene pathways after NPS stimulation. Our results show that NETs are a source of NPS and NPSR1, and that NPS affects cancer-related pathways.

Identification of risk factors for an unsuccessful transition from pediatric to adult sickle cell disease care.

BACKGROUND: A successful transition from pediatric to adult sickle cell disease (SCD) care is paramount to continued improvements in survival. In order to enhance transition success, our pediatric SCD transition process was modified to include combined adult and pediatric provider clinics that incorporated participation by our local SCD community-based organization. All children ages 16 and over participated in this newly-formed transition program. PROCEDURE: After 5 years of implementation of the modified SCD transition program, we retrospectively studied clinical and non-clinical risk factors for an unsuccessful transition. Risk factor categories studied included patient demographics, transition clinic attendance, and disease severity. RESULTS: Thirty-two percent of patients did not transition successfully. Demographic factors such as gender, race, and type of insurance did not influence transition outcome, although travel distance to the adult SCD center was an identifiable risk factor for an unsuccessful transition. While transition clinic attendance rate did not affect transition outcomes, older age at first modified combined transition clinic visit was a significant risk factor for lack of transition. Patients with clinical markers of milder disease severity (SC and Sß(+) genotypes and no chronic transfusion therapy) were at higher risk for an unsuccessful transition than patients with severe disease. CONCLUSIONS: We have identified several risk factors for lack of transition success which will allow us to modify our transition efforts going forward to capture this highest risk subset.

Mature human odontoblasts express virus-recognizing toll-like receptors.

AIM: To study the expression of toll-like receptors (TLR) -3, -7, -8 and -9 as well as interferon receptors alpha and gamma (IFNAR1/IFNAR2 and IFNGR1/IFNGR2), which play important roles in the defence against viruses. METHODOLOGY: DNA microarray and quantitative PCR analyses of TLR3, -7, -8 and -9 as well as IFNAR1/IFNAR2 and IFNGR1/IFNGR2 genes in mature native human odontoblasts and pulp were performed. Immunohistochemistry was used to confirm TLR8 protein in odontoblasts of healthy and carious human teeth. RESULTS: TLR3, -7, -8 and -9 mRNAs were detected both in odontoblasts and in pulp, but TLR8 expression level was higher in the odontoblasts. IFNAR and IFNGR expression was observed in both tissues. Immunohistochemical analysis of healthy teeth revealed positive TLR8 staining in the pre-dentine and the dentine but varying staining patterns in the different portions of tooth. Lighter TLR8 staining was observed in dentine of mildly carious teeth. In teeth with carious lesions extending into the mid-dentine, only very weak staining was detected. CONCLUSIONS: The finding of these virus-recognition-related genes in odontoblasts strengthens the view that odontoblasts participate in the immune response of the dentine-pulp complex.

Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.

Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.

CT findings of necrotizing sialometaplasia.

An otherwise healthy 56-year-old Caucasian female was referred to the radiology department because of an ulceration of her palatal mucosa. Clinically the lesion was suspected to be malignant and a multislice CT examination of the head and neck region was performed. This revealed an ulcer-like cavity with no tumour-like contrast enhancement. No relevant bone changes or suspicious lymph nodes of the neck were detected. Based on the multislice CT findings, necrotizing sialometaplasia was suspected and the diagnosis was verified histopathologically. This report describes the CT findings of necrotizing sialometaplasia at the ulceration stage.

High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer.

BACKGROUND: No reliable prognostic markers exist for squamous cell carcinoma of the tongue, and its prognosis can even in early stages be unpredictable and survival poor despite treatment. A potential marker is oncoprotein cancerous inhibitor of PP2A (CIP2A), which acts as a prognostic marker in gastric and non-small cell lung cancers. METHODS: We collected specimens of 73 stage T1N0M0 and T2N0M0 oral squamous cell carcinomas of the tongue, as well as samples from normal oral mucosa, dysplastic lesions, and invasive carcinomas (n=39). All samples were stained for CIP2A by immunohistochemistry. Survival curves were constructed according to the Kaplan-Meier method. The Cox proportional hazard model served for univariate and multivariate survival analysis. RESULTS: High CIP2A immunoreactivity predicted poor survival in tongue cancer patients (P=0.027, logrank test). In multivariate survival analysis, CIP2A was an independent prognostic factor (HR 2.02, 95% confidence interval 1.07-3.82, P=0.030). Cytoplasmic CIP2A expression was higher in severe dysplasia than in mild dysplasia. CONCLUSION: Our results suggest that high CIP2A expression characterises aggressive disease. Acting as a prognostic marker it might be of help when choosing patients for adjuvant treatment in tongue cancer patients.

Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue.

BACKGROUND: The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial-mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. METHODS: Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. RESULTS: A significant correlation between Bmi-1 protein expression and recurrence (log-rank test, P=0.005) was detected. Snail and c-myc expression did not correlate with prognosis. Snail expression correlated with histopathological grade (Fisher's exact test, P=0.007) and with the invasion depth of tumours (chi(2)-test, P=0.037). CONCLUSION: Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.

Use of low-dose ketamine infusion for pediatric patients with sickle cell disease-related pain: a case series.

OBJECTIVES: Sickle cell disease-related pain is difficult to treat adequately. Pain secondary to vasoocclusive episodes (VOE) may be unresponsive to high-dose intravenous opiates. Alternative treatment options for VOE are needed. We sought to review our experience with low-dose ketamine for children hospitalized with VOE. METHODS: Retrospective medical chart reviews were conducted for hospitalized patients treated with ketamine for sickle cell VOE. Data gathered included vital signs, pain scores, opiate utilization, and adverse events. RESULTS: Five children and adolescents received a low-dose ketamine infusion for the treatment of sickle cell-related pain. Four received the infusion in addition to opiates (delivered via patient controlled analgesia) as a rescue intervention after several days of inadequate pain relief and 1 patient received ketamine in place of opiates. Two of the 5 patients achieved what seems to be clinically significant pain control with a low-dose ketamine infusion, whereas 1 additional patient had significant reduction in opiate utilization. DISCUSSION: Further research into ketamine for vasoocclusive pain is warranted.

Anaplastic and poorly differentiated thyroid carcinoma: therapeutic strategies and treatment outcome of 52 consecutive patients.

Anaplastic thyroid carcinoma (ATC) is one of the most lethal malignancies; poorly differentiated thyroid carcinoma (PDTC) is a new diagnosis for rare aggressive thyroid tumours. Surgery is often considered the only chance for survival, but the benefit of surgery and subsequent multimodal therapy is unclear. We retrospectively analyzed the outcome of 44 ATC and 8 PDTC consecutive patients treated at Helsinki University Central Hospital between 1990 and 2008. All ATC and PDTC cases were re-examined and reclassified histologically. Median survival was only 3.1 months for ATC, but 3.7 years for PDTC. Most patients in both groups eventually died of cancer. ATC patients were older than PDTC patients (74 vs. 66 years). Nodal and distant metastases had a negative impact on survival (ATC; p = 0.038, p = 0.008). Long-term survivors in both groups were stage N0M0 at presentation. Multimodal therapy was successful for 9 (20%) ATC patients, and their median survival was the longest (11.6 months) among treatment groups. Most PDTC patients (88%) underwent total thyroidectomy followed by radioiodine ablation; the only 2 who received chemotherapy survived longest. Although ATC and PDTC are both aggressive thyroid carcinomas, multimodal therapy for both can provide a chance of prolonged survival in patients with locoregional disease.