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Background A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration Clinicaltrial.gov: NCT03339063.

Introduction: Adequate brushing of oral mucosa is important for accurate human papillomavirus (HPV) detection in potentially malignant (oral leukoplakia [OL], oral lichen planus [OLP]) and malignant (oral squamous cell carcinoma [OSCC]) lesions. Since various factors may limit the adequacy of oral brushing and, consequently, the accuracy of HPV detection, modified sampling procedures should be evaluated for their effect on HPV frequency and/or types detected. Aim: To compare the HPV frequency in samples obtained by brushing the lesion site with the frequency in samples obtained by brushing an apparently normal adjacent site. The correlation between HPV frequency and keratinization of the site affected by the lesion, as well as sociodemographic variables (age, sex, smoking and drinking habits), was also examined. Methods: HPV DNA was detected in brushing samples from 50 patients with OL, 49 with OLP, and 17 with OSCC. Polymerase chain reaction (PCR) amplification was performed by MY09/MY11 and GP05+/GP06+ primers; the HPV type was identified by DNA sequencing and a reverse hybridization (line probe) assay. Data were analyzed by the Z test, the Fisher’s exact test, the chi-square test, odds ratio (OR), and a logistic regression model. Results: HPV DNA was detected in 22% of samples from lesion sites and in 16% of samples from adjacent sites (p = 0.22) in patients with OL, in 24.5% and 22.4% of samples from lesion and adjacent sites, respectively, in patients with OLP (p = 0.40), and in 35.3% and 41.2% of samples from lesion and adjacent sites, respectively, in patients with OSCC (p = 0.36). Lesions adjacent to HPV-positive normal sites had an increased rate of HPV detection (OR = 30; 95% CI 9.57, 94.1). HPV-18 was the most frequent genotype, followed by HPV-6, -16, -33, and -53. HPV prevalence was reduced in lesions at keratinized sites (14.5%) compared with non-keratinized sites (34.4%; p = 0.007; OR = 0.32; 95% CI 0.13, 0.81). Discussion: In patients with OL, OLP, or OSCC, a high prevalence of HPV infection was shown in apparently normal sites adjacent to lesion sites infected by HPV. The lower HPV frequency in lesions at keratinized sites suggests that HPV detection by lesion brushing is affected by keratinization. The keratinized epithelium may be less susceptible to HPV infection or, alternatively, the highly proliferative activity in non-keratinized sites may predispose to HPV infection. Conclusion: Results from this study indicate that taking samples from normal sites adjacent to oral lesions may be of value in HPV detection, particularly when the lesions are located at keratinized sites. This sampling procedure may allow more accurate diagnosis of HPV infection compared with sampling only the lesion site, and may also represent a reliable method to investigate the biological characteristics of HPV infection and related oral carcinogenesis.

In the field of maxillofacial reconstructive surgery, the authors take into consideration the autogenous calvarial bone graft harvest technique for the correction of maxilla bone defects and examine some salient aspects such as technical problems and possible surgical complications.

Background The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. Methods Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. Results DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. Conclusion These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

Background: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. Methods: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. Results: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values5) in K-OLPs and nK-OLPs, respectively. The PSQI’s validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. Conclusions: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Background: Multi-phasic Computed Tomography (CT) evaluation allows to study the enhancement features of parotid gland masses. The aim of our study was to evaluate the role of delayed enhancement in the characterization of different histologic types of parotid tumours. Methods: Forty-eight patients (22 male and 26 female) with at least one parotid gland tumor, were included in our study. Multi-phase CT images were obtained before and 30, 120 s and 8 minutes after intravenous contrast injection. The images were evaluated by two radiologists for lesion enhancement degree. A quantitative assessment was performed using a region of interest on each lesion and density changes between different phases were compared. The tumoral enhancement ratio was calculated between the 8 minutes delayed and the early (30 s) phase. The pathological diagnosis was confirmed in all patients after surgery. Results: All patients had unilateral lesion for a total of 48 lesions. Twenty-eight were pleomorphic adenomas, 15 Warthin's tumours and 5 carcinomas. All Warthin tumours showed a rapid contrast enhancement at the early phase (30 sec) followed by a progressive wash-out during the delayed scans. Most of pleomorphic adenomas (89.2%) showed the highest density at the 8-minutes delayed phase. Malignant tumours showed slower contrast enhancement and 3 out of 5 (60%) showed a marked decrease at the 8 minutes delayed phase while the remaining 2 (40%), did not show any density reduction. The tumoral enhancement ratio was significantly different between Warthin tumours and pleomorphic adenomas and between Warthin's and malignant tumours. Conclusions: Multi-phasic CT examination with 8 minutes delayed acquisition has shown to be useful in parotid gland lesion differentiation. Background: Multi-phasic Computed Tomography (CT) evaluation allows to study the enhancement features of parotid gland masses. The aim of our study was to evaluate the role of delayed enhancement in the characterization of different histologic types of parotid tumours.Methods: Forty-eight patients (22 male and 26 female) with at least one parotid gland tumor, were included in our study. Multi-phase CT images were obtained before and 30, 120 s and 8 minutes after intravenous contrast injection. The images were evaluated by two radiologists for lesion enhancement degree. A quantitative assessment was performed using a region of interest on each lesion and density changes between different phases were compared. The tumoral enhancement ratio was calculated between the 8 minutes delayed and the early (30 s) phase. The pathological diagnosis was confirmed in all patients after surgery.Results: All patients had unilateral lesion for a total of 48 lesions. Twenty-eight were pleomorphic adenomas, 15 Warthin's tumours and 5 carcinomas. All Warthin tumours showed a rapid contrast enhancement at the early phase (30 sec) followed by a progressive wash-out during the delayed scans. Most of pleomorphic adenomas (89.2%) showed the highest density at the 8-minutes delayed phase. Malignant tumours showed slower contrast enhancement and 3 out of 5 (60%) showed a marked decrease at the 8 minutes delayed phase while the remaining 2 (40%), did not show any density reduction. The tumoral enhancement ratio was significantly different between Warthin tumours and pleomorphic adenomas and between Warthin's and malignant tumours.Conclusions: Multi-phasic CT examination with 8 minutes delayed acquisition has shown to be useful in parotid gland lesion differentiation.

BACKGROUND: P63 is the protein codified by p63 gene, a p53 gene homolog, known for its pivotal role in cell cycle regulation, and involved in the tumor differentiation. Aims of the present study were to assess the frequency and pattern of p63 protein expression in oral squamous cell carcinoma (OSCC) in relation to the main tumour characteristics and to verify whether p63 can be considered a marker of prognosis in patients with OSCC. MATERIAL AND METHODS: In a retrospective study, a cohort of 64 OSCC patients was investigated for p63 protein expression and its cellular localization by immunohistochemistry (monoclonal mouse anti-human p63 protein-clone 4A4). After grouping by p63 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. RESULTS: The overall frequency of p63 overexpressed was of 57.8 percent. Various p63 staining patterns were observed according to G score, with a significant correlation between p63 overexpression and the lowest G score (P < 0.0001). No statistically significant difference was found between p63 pattern expression and age, sex, staging. OSCC patients with p63 overexpressed were found to have a poorer survival rate with respect to OSCCs with a normal pattern of expression (P = 0.024). CONCLUSIONS: On the basis of these results, it is possible to suggest p63 pattern expression as a reliable indicator of histological grading and an early marker of poor prognosis.

Introduction: The management of squamous cell carcinoma (SCC) of the tongue represents the most demanding treatment planning in head and neck surgery. Ablation followed by free flap reconstruction is considered the gold standard, but not all patients are suitable for this strategy. The aim of this review is to provide a comprehensive view of surgical reconstruction possibilities in patients not eligible for free flaps. Methods: Following PRISMA recommendations, a systematic literature review was conducted searching for original papers that investigated outcomes of patients treated by surgical ablation for tongue SCC followed by reconstruction with local or pedicled flaps. Selected papers were read and data extracted for qualitative analysis. Results: Twenty articles met the inclusion/exclusion criteria. The study design was case series in sixteen papers, cohort study in the remaining four. Four different local flaps (BMM, FAMM, NLIF, SMIF) and four regional flaps have been discussed in included studies (IHF, SFIF, SCM, PMMC). Conclusion: The improved anatomical knowledge makes local flaps a reliable alternative to free tissue transfer in cases requiring small-/medium-sized defects. Regional flaps still represent cornerstones in reconstruction of the tongue. Ease of execution, costs-to-benefit ratio, low-rate complications, minimal donor site morbidity represent the best advantages choosing local/regional flaps.

The aim of this study is to analyze surgical and functional outcomes in order to verify the applicability of surgical treatment guidelines as foreseen by MASCC/ISOO/ASCO 2019. Patients affected by stage 2 MRONJ refractory to conservative management were grouped if underwent surgical resection (Group A) or debridement (Group B). Health-related quality of life was evaluated by using the European Organization for Research and Treatment of Cancer questionnaires, QLQ-C30 and H&amp, N35. Statistical analysis was performed using Wilcoxon/Mann–Whitney test, Kaplan–Meier test, Cox regression model and Cox multivariate regression. Group A showed higher complete healing cases vs. group B. Recurrence rate difference in group A vs. group B was statistically significant. Debridement is an unfavorable prognostic factor when compared to surgical resection (p = 0.0032, HR 4.9). Quality of life mean values showed a marked improvement in Group A and a slight improvement in Group B. Debridement has 4.9 times more risk to develop recurrence when compared to surgical resection. A more satisfactory quality of life was shown in patients subject to resective surgery with an improving trend from baseline. Debridement patients showed more variability of results and an overall negative trend at the end of the 6-month follow-up.

Simple Summary Oral cancer may strongly impair patients’ quality of life. Huge efforts have been made during recent decades in trying to improve the treatment outcomes in terms of patients’ survival, self-perception, and satisfaction. Consequently, the investigation into health-related quality of life (HRQOL) became an established and worldwide practice. Hundreds of studies tried to clarify which could be the most important variables that impact HRQOL in head and neck cancer patients. However, such a complex topic may be influenced by a multitude of interconnected aspects and several controversies were reported. In this study the current literature was reviewed to identify all those possible sources of bias that may be encountered in trying to correlate HRQOL to patient-specific or disease/treatment-specific aspects. As a result, a list of recommendations was reported to enhance the evidence of future studies. Abstract Background: health-related quality of life (HRQOL) represents a secondary endpoint of medical interventions in oncological patients. Our aim was to highlight potential sources of bias that could be encountered when evaluating HRQOL in oral cancer patients. Methods: this review followed PRISMA-ScR recommendations. Participants: patients treated for oral cancer. Concept: HRQOL assessed by EORTC QLQ-C30 and QLQ-H&N35/QLQ-H&N43. A critical appraisal of included studies was performed to evaluate the accuracy of data stratification with respect to HRQOL determinants. Results: overall, 30 studies met the inclusion criteria, totaling 1833 patients. In total, 8 sociodemographic (SDG) and 15 disease/treatment-specific (DT) HRQOL determinants (independent variables) were identified. The mean number of the independent variables was 6.1 (SD, 4.3)—5.0 (SD, 4.0) DT-related and 1.1 (SD, 1.8) SDG-related variables per article. None of the included papers considered all the identified determinants simultaneously. Conclusions: a substantial lack of evidence regarding HRQOL determinants was demonstrated. This strongly weakens the reliability of the reported findings due to the challenging presence of baseline confounding, selection, and omitted variable biases. The proposed approach recommends the use of further evaluation tools that gather more variables in a single score together with a selection of more homogeneous, reproducible, and comparable cohorts based on the identified baseline confounding.

Oral malignant melanoma (OMM) is an aggressive tumour, and shows deep tissue invasion at initial presentation. The prognosis is worse than that for cutaneous melanoma (CM), and the overall 5-year survival rate is 10-25%. A study of the molecular mechanisms involved in the development of OMM is necessary to identify new prognostic markers. In this study, we evaluated the possible role of nicotinamide N-methyltransferase (NNMT) in OMM. We carried out immunohistochemical analyses to evaluate the expression of NNMT in 15 OMM and 15 CM, measuring the percentage of positive cells and the value of NNMT expression intensity. Furthermore, we explored the relationship between NNMT levels and the prognostic parameters of patients with OMM. NNMT was significantly more expressed in CM compared with OMM, whereas higher staining intensity for NNMT was observed in OMM cases (P

(1) Background: There is an increasing demand for a reversal of the aging process and, nowadays, more patients are seeking minimally invasive methods instead of surgery to meet this goal. The purpose of this paper is to evaluate the predictability of the off-label aesthetic use of botulinum toxin type A (BoNTA) reconstituted with lidocaine. (2) Methods: One thousand treatments, between January 2010 and January 2020, with BoNTA reconstituted with lidocaine for the rejuvenation of the upper third of the face, were performed and retrospectively evaluated. (3) Results: A few seconds after the BoNTA injections, the effect of muscle paralysis was seen in all cases, this allowed providing an optimal symmetric result with no need for a touch-up procedure at the control after three weeks. A burning sensation during the injections was claimed by almost all patients. Major complications were not registered. No touch-up procedures were required. (4) Conclusions: The results of this study show how the reconstitution of BoNTA with lidocaine may avoid imperfect results after the injections, the immediate feedback on the extent of paralysis to be expected from the chemodenervation action of BoNTA allows the physician to have immediate control of the final result.

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy.

Background: Although the published literature has grown exponentially during the last few decades, managing medication-related osteonecrosis of the jaws (MRONJ) remains challenging. Since the first description of adipose-derived stem cells, cell therapy showed promising perspectives in surgical treatment of MRONJ. In this study, the beneficial effect of fat graft in surgical treatment of stage 2 and 3 MRONJ patients was assessed. Methods: A retrospective analysis of the evolution pattern of the disease was conducted comparing the outcomes of MRONJ patients who underwent sequestrectomy followed by fat graft (n = 9) and those who received sequestrectomy alone (n = 12). Results: Improvement of the disease stage was observed in 77.8% vs. 22.2% cases in group A and B, respectively (p = 0.030); disease stability was documented in 11.1% vs. 25.0% cases in group A and B, respectively (p = 0.603); worsening of MRONJ stage was observed in 11.1% vs. 50.0% cases in group A and B, respectively (p = 0.159). Conclusions: Despite the small sample size, this study suggests that fat graft may represent a promising low-risk and cost-efficient adjunctive therapy in the surgical treatment of MRONJ patients.

Objectives: To analyze psychological profiles, pain and oral symptoms in patients with oral lichen planus (OLP). Materials and methods: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes) and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered. Results: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value

Background To evaluate the viability and efficacy of sialendoscopy for the management of parotidomegaly related to eating disorders, 6 patients suffering from eating disorders and recurring symptoms of glandular swelling were followed up at the Multidisciplinary Department of Medical-Surgical and Dental Specialties, Oral and Maxillofacial Surgery Unit, AOU University of Campania “Luigi Vanvitelli”. After the detection of the impaired gland through clinical and radiographical analysis, the diagnostic unit was introduced into the duct and was advanced in, reaching the ductal system. Plaques were washed out, any strictures were dilated both by hydrostatic pressure application and steroid solution injection directly in the fibrotic area. Results Both glands resulted affected in 83% of patients. 11 parotid glands were explored and treated. Strictures were found in 2 glands (33%), sialectasis in 3 glands (50%), strictures and sialectasis together in 1 glands (17%). In 3 parotid glands (50%) Stenon’s duct was affected, in two (33%) only secondary ducts, in 1 (17%) both. We reached symptomatic improvement in 5 patients (83%), reporting the spherical volume of the parotid region and pain reduction. Conclusions Our results demonstrate that sialendoscopy is a safe and effective therapeutic method to treat EDs salivary symptoms. Treating the underlining psychiatric pathology should be the primary goal in patient care to lower the possible recurrence rate and increase the successful outcome of this technique.

Highlights • In COVID-19 era, the aim of our effort is to guarantee high-quality and timely oncologic care, minimizing infection risk. • Microvascular flaps, reported to be the gold standard for reconstruction, require an extended resource allocation not affordable in this period. • We are obliged to define a paradigm shift in our approach, based on propeller flap. • This surgical technique could represent a reconstructive landmark in COVID-19 era, besides head and neck reconstructive surgery is most likely heading towards a new reconstructive approach., In COVID-19 pandemic era, one major concern is related to ensure optimal management to oncologic patients, even though a context of radical uncertainty. The aim of our effort is to guarantee high-quality and timely care, minimizing COVID-19 infection risk, according to our head and neck (HN) reconstructive mission, still more challenging because of the criticality of the period. Thus, our reconstructive decision algorithm is changed. Microvascular free flaps, reported to be the gold standard for surgical reconstruction, represent extremely specialized procedures necessitating an extended resource allocation not affordable in the adversities of the period. Therefore, we are obliged to define a paradigm shift in our approach, based on free-style reconstructive surgery principles of propeller flap concept. According to our experience, we believe that this viable and feasible surgical technique could represent a reconstructive landmark in this pandemic era, since any guideline is missing, besides HN reconstructive surgery is most likely heading towards a new reconstructive approach.

Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC.

Metastases to orofacial tissues are infrequent, their incidence being 1&ndash, 8% of malignant oral tumors, sometimes manifesting as the first clinical sign of an occult cancer. Renal cell carcinoma (RCC) is the second most common metastatic carcinoma to the oro-facial tissues, involving the jawbones, gingiva, oral mucosa, tongue or salivary glands. Also, RCC frequently displays a prominent clear cell component, which may predominate in the clear cell renal cell carcinoma subtype (CCRCC) and histologically mimic many other clear cell tumors, both benign and malignant, which can be epithelial (from keratinizing epithelia, cutaneous adnexa, salivary glands and odontogenic epithelium), melanocytic or mesenchymal in origin. In view of the necessity for prompt and accurate diagnosis of such unusual neoplasms, we report on the salient clinico-pathological features of 7 CCRCC metastatic to the oro-facial tissues, and highlight their immunohistochemical profile, to more accurately discriminate this neoplasm from other tumors of the oral cavity with a prominent clear cell component.

Skin necrosis is the most severe complication arising from hyaluronic acid (HA) injection. To avoid skin necrosis, hyaluronidase should be injected along the course of the involved artery, to allow blood flow restoration. We evaluated the ability of hyaluronidase to degrade a HA filler in two simulated clinical situations-a compression case and an embolization case-to identify differences in the hyaluronidase injection. In the compression case, a bolus of HA filler was directly soaked in hyaluronidase solution; in the embolization case, a vein harvested from a living patient was filled with the same HA filler and then soaked in hyaluronidase. We then evaluated the quantity of HA remaining after 2 hr. While we found hydrolysis of HA in both cases, in the compression case, we detected almost complete hydrolysis, whereas in the embolization case we observed a reduction of the 60%. Our results support the hypothesis that vessel compression can be resolved with only one injection of hyaluronidase, while in the case of vascular embolization, repeated perivascular injections should be performed owing to the reduction of hyaluronidase activity.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Background: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour in paediatric population, accounting for 16% of all cases. Patients affected by a previous solid or leukaemic neoplasm during their childhood may develop a second different tumour during the follow-up. In this setting, salivary gland MEC is relatively frequent, accounting for 6% of the second neoplasms in paediatric patients. Consequently, the occurrence of salivary gland nodules in paediatric patients with a previous neoplasm should be considered an event with a high risk of malignancy that poses peculiar diagnostic challenges. Summary: This study was designed to define clinical and instrumental findings and morphological features of MEC on fine-needle aspiration cytology (FNAC) samples in paediatric patients with and without a previous neoplasm. Five patients under 19 years are included in this series. FNAC was performed in all patients on a parotid nodule. We have identified 2 groups of patients: (a) 2 cases with previous history of malignancy (acute lymphoblastic leukaemia and Hodgkin lymphoma) and (b) 3 cases without previous malignant neoplasms. In all cases, a final diagnosis of MEC was rendered. Key Messages: MEC may occur as a second malignancy in paediatric patients. FNAC is certainly a valid and accurate diagnostic tool for this type of neoplasm, even in the paediatric age, allowing the correct management of the patients.

Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1–15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.

Standard chemotherapy treatment for Diffuse large B-cell lymphoma (DLBCL), including cyclophosphamide, doxorubicin, vincristine and prednisone, in association with rituximab (CHOP-R) are considered associated to the development of secondary tumors. In this clinical setting, therapy-related myeloid neoplasms (t-MNs) represent one of the most common secondary tumors. In this case we describe, A 58-year-old patient diagnosed with DLBCL and treated with the CHOP-R therapeutic scheme, developed after 4 years a widespread gingival enlargement, diagnosed as acute myelomonocytic leukemia and then confirmed by overall clinical-pathological features. Therapy related neoplasms can be an aggressive complication of cytotoxic treatments of neoplastic and non-neoplastic diseases. Gingival hyperplasia could represent an early manifestation of these systemic pathologies.

Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC), the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC (mean age: 62 years, M/F: 2.39∶1) were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included: sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges: dichotomous (≤1 month vs. >1 month) and polytomous (3 months) delay. Data were investigated by univariate and multivariate analyses and a P value ≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were: 'Personal experience of cancer' (dichotomous delay: P=0.05, odds ratio (OR)=0.33, 95% confidence interval (CI)=0.11-0.99; polytomous delay: P=0.006, Chi-square=10.224) and 'Unawareness' (dichotomous delay: P

Introduction Obesity and osteoporosis share many features and recent studies have identified many similarities suggesting common pathophysiological mechanisms. Obesity is associated with a higher risk of non-traumatic fractures despite bone mineral density (BMD) being normal or even increased. Materials and methods 54 obese subjects were analyzed (51 ± 16 years, 10 males, 44 females). Spinal deformity index (SDI) is a semi-quantitative method that may be a surrogate index of bone microarchitecture. SDI index was higher in patients than in controls. In 87.5 % of patients and 10 % of controls we found morphometric vertebral fractures, despite a DEXA Tscore not diagnostic of osteoporosis. Conclusion The objective of this study was to assess in obese patients levels of 25OH vitamin D, parathyroid hormone, serum and urinary calcium (Ca) and phosphorus (P), BMD, and SDI. 87.5 % of the obese subjects present nontraumatic vertebral fractures and reduced bone quality as measured by SDI.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

Oral mucositis (OM) is a very frequent and potentially severe complication experienced by patients receiving chemotherapy and/or radiotherapy, which often leads to significant morbidity and mortality, and decreased quality of life, and is very costly. Despite its severity and prevalence, there is no standard recognised management today. The aim of this open clinical trial is to evaluate the efficacy and compliance of a new spray compound containing sodium hyaluronate (SH) and a pool of collagen precursor amino acids (AAs) combined with sodium hyaluronate (SH) to manage radio/chemotherapy-induced OM. Twenty-seven consecutive patients with OM were treated according to the manufacturer's instructions. At time TO (baseline — before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0–100) and (ii) severity of OM scored according to WHO Mucositis scale. The treatment efficacy was evaluated on i) pain score, ii) clinical resolution index (CRI) and iii) patient compliance at times T01 (after 2 hours), T1 (after 24 hours), T2 (after 72 hours), T3 (after 7 days) and T4 (after 14 days). Results showed that painful symptoms were significantly reduced after only 2 hours of spray administration compared with baseline measurements ( p

Objective: This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. Materials and Methods: Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO-RAD Data Manager™ (Version 3.5). Results: We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA. Conclusion: Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis. Objective: This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. Materials and Methods: Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO-RAD Data Manager™ (Version 3.5). Results: We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA. Conclusion: Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis.

Background/aim: Oral candidiasis is the most common fungal infection in dental practice, and is caused by yeasts that are normally present in the endogenous flora. Methods: To evaluate a rapid diagnostic method for identification of Candida oral isolates, a multiplex polymerase chain reaction (PCR) was carried out on colonies and on oral rinse solutions from 95 subjects with suspected oral candidiasis and results were compared with those from seven commonly used phenotypic identification systems. Results: Between four and nine species were characterized in the samples by the phenotypic methods. PCR identified the same species in 60 (74%) samples from both colony and oral rinse solutions. Statistical analysis, carried out only for the three most frequently isolated species (Candida albicans, Candida glabrata, and Candida tropicalis), showed good concordance in the comparison of multiplex PCR with API 20C AUX and with the Rapid Yeast Identification Panel; conversely, significant differences were registered in the comparison between the molecular method and other phenotypic systems, including four chromogenic media and the automated system Vitek2. Discussion: Multiplex PCR was rapid and effective in the identification of Candida species and allowed the detection of more than one species in the same sample.

Background Bisphosphonates (BPs) are currently the chief drugs for the prevention/treatment of osteoporosis; one of their adverse effects is the osteonecrosis of the jaw (BRONJ). The primary endpoints of this multi-center cross-sectional study are: i) an observation of the clinical features of BRONJ in 87 osteoporotic, non-cancer patients; and ii) an evaluation of their demographic variables and comorbidities. Methods 87 BRONJ patients in therapy for osteoporosis with BPs from 8 participating clinical Italian centers were consecutively identified and studied. After BRONJ diagnosis and staging, comorbidities and data relating to local and drug-related risk factors for BRONJ were collected. Results 77/87 (88.5%) patients in our sample used alendronate as a BP type; the duration of bisphosphonate therapy ranged from 2 to 200 months, and 51.7% of patients were in treatment for ≤ 38 months (median value). No comorbidities or local risk factors were observed in 17 (19.5%) patients, indicating the absence of cases belonging to BRONJ forms triggered by surgery. BRONJ localization was significantly associated with age: an increased risk of mandible localization (p = 0.002; OR = 6.36, 95%CI = [1.89; 21.54]) was observed for those over 72 yrs. At multivariate analysis, the increased risk of BRONJ in the mandible for people over 72 yrs (OR′ = 6.87, 95%CI = [2.13; 2.21]) was confirmed for a BP administration > 56 months (OR′ = 4.82, 95%CI = [2.13; 22.21]). Conclusion Our study confirms the fundamental necessity of applying protocols of prevention in order to reduce the incidence of BRONJ in osteoporotic, non-cancer patients in the presence of comorbidities and/or local risk factor as well as, less frequently, in their absence.

E-3810 is a novel small molecule that inhibits VEGF receptor-1, -2, and -3 and fibroblast growth factor receptor-1 tyrosine kinases at nmol/L concentrations currently in phase clinical II. In preclinical studies, it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model. The molecule could be safely administered with 5-fluorouracil, cisplatin, and paclitaxel. The E-3810–paclitaxel combination showed a striking activity with complete, lasting tumor regressions; the antitumor activity of the combination was also confirmed in another triple-negative breast xenograft, MX-1. The activity was superior to that of the combinations paclitaxel+brivanib and paclitaxel+sunitinib. Pharmacokinetics studies suggest that the extra antitumor activity of the combination is not due to higher paclitaxel tumor levels, which in fact were lower in mice pretreated with all three kinase inhibitors, and the paclitaxel plasma levels excluded reduced drug availability. Pharmacodynamic studies showed that E-3810, brivanib, and sunitinib given as single agents or in combination with paclitaxel reduced the number of vessels, but did not modify vessel maturation. Reduced tumor collagen IV and increased plasma collagen IV, associated with increased matrix metalloproteinases (MMP), particularly host MMP-9, indicate a proteolytic remodeling of the extracellular matrix caused by E-3810 that in conjunction with the cytotoxic effect of paclitaxel on the tumor cells (caspase-3/7 activity) may contribute to the striking activity of their combination. These data support the therapeutic potential of combining E-3810 with conventional chemotherapy. Mol Cancer Ther; 12(2); 131–40. ©2012 AACR.

Intravenous bisphosphonates (BP) play a key role in the treatment of bone metastases. As a long-term side effects BP, a form of avascular osteonecrosis of the jaw has been reported. Although, invasive oral local procedures are often present in clinical history of patients suffering from bisphosphonates-related osteonecrosis of the jaws (BRONJ), about up to 50% of BRONJ are spontaneous. We report a case of a 68-year-old female with a spontaneous wide bone sequestration of the left mandibular body onset after infusion of zoledronic acid for 18 cycles for osseous metastasis due to metastatic anaplastic thyroidal carcinoma. Surprisingly the clinical aspects of the patient initially reminded us of the famous pathology described in 1899 called phossy jaw. This case is remarkable not only for the spontaneity of the osteonecrosis, but, above all, for the clinical similarity with cases of phossy jaw, described for the first time in the literature, thereby suggesting a potential common pathogenesis.

PURPOSE: The aim of this study was to evaluate the results of the surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a large cohort. MATERIALS AND METHODS: A retrospective cohort multicenter study was designed. Patients were enrolled if they were diagnosed with BRONJ and received operative treatment. Data on demographic, health status, perioperative, and surgical factors were collected retrospectively. The primary outcome variable was a change in BRONJ staging (improvement, worsening, or no change). Interventions were grouped by local debridement and resective surgery. Data were collected for other variables as cofactors. Univariate analysis and logistic regressions were then performed. RESULTS: Of the 347 BRONJ-affected subjects, 59% showed improvement, 30% showed no change, and 11% showed worsening. Improvement was observed in 49% of cases treated with local debridement and 68% of cases treated with resective surgery. Multivariate analysis indicated that maxillary location, resective surgery, and no additional corticosteroid treatment were associated with a positive outcome. CONCLUSIONS: Surgical treatment of BRONJ appeared to be more effective when resective procedures were performed. Nonetheless, other factors, such as the absence of symptoms and the types of drug administration, should be taken into account before clinical decisions are made.

Introduction Bisphosphonates (BPs) are powerful drugs that inhibit bone metabolism. Adverse side effects are rare but potentially severe such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, research has primarily focused on the development and progression of BRONJ in cancer patients with bone metastasis, who have received high dosages of BPs intravenously. However, a potential dilemma may arise from a far larger cohort, namely the millions of osteoporosis patients on long-term oral BP therapy. Patients and methods This current study assessed 470 cases of BRONJ diagnosed between 2004 and 2008 at eleven different European clinical centres and has resulted in the identification of a considerable cohort of osteoporosis patients suffering from BRONJ. Each patient was clinically examined and a detailed medical history was raised. Results In total, 37/470 cases (7.8%) were associated with oral BP therapy due to osteoporosis. The majority (57%) of affected individuals did not have any risk factors for BRONJ as defined by the American Association of Oral and Maxillofacial Surgery. The average duration of BP intake of patients without risk factors was longer and the respective patients were older compared to patients with risk factors, but no statistical significant difference was found. In 78% of patients the duration of oral BP therapy exceeded 3 years prior to BRONJ diagnosis. Discussion The results from this study suggest that the relative frequency of osteoporosis patients on oral BPs suffering from BRONJ is higher than previously reported. There is an urgent need to substantiate epidemiological characteristics of BRONJ in large cohorts of individuals.

Sexual hormones play an important role in expression of genes involved in a wide variety of biological and neoplastic processes. The information on Estrogen Receptors (ER) expression in non-target tissues is very few and, in particular, the studies in head and neck tumors are still controversial. Recent studies analyzed the role of Tamoxifen (TAM) on Oral Squamous Cell Carcinoma (OSCC) lines in relation to the presence/absence of ER. The purpose of the present study was to evaluate the expression of sexual hormones receptors mRNAs, in particular Estrogen Receptor alpha (ERα) and Androgen Receptor (AR) mRNA in OSCC tissues. The study group comprised 20 samples of OSCC, harvested from 20 otherwise healthy subjects (14 males and 6 females, mean age 58.2y, range 38–74). The control group was formed by 20 samples of normal mucosa harvested around the margins of the specimens (at least 1 cm from the lesion margins). Estrogens Receptor alpha (Era) and Androgen Receptor (AR) mRNA expressions were analyzed by RT-PCR carried out on total RNAs extracted from both cancerous and healthy tissues. Obtained data were evaluated by Shapiro-Walk normality test and compared by Student's t test. Results with p

This study analyzes the efficacy of occlusal devices for the long-term stability of contouring of the lower face by injection of Botulinum toxin type A in a prospective clinical protocol. Ten patients (seven female and three male) with a widened lower face were recruited consecutively between January 2006 and January 2007. Each patient was advised to wear an occlusal device to release masticatory muscles, and percutaneous intramuscular injections of Botulinum toxin type A were used. The follow-up study was 18 months. Facial changes were noted by the patients as early as 2 weeks after the injection and lasted for 18 months; all patients reported an improved facial profile. There were no complications. Botulinum toxin type A injection for the contouring of the lower face is a simple technique, has few side effects, and allows a rapid return to daily life. In our study, the long-term stability of the result is related to the occlusal therapy performed after the injection of botulinum toxin type A.

With reference to the 2009 update of the American Association of Oral and Maxillofacial Surgeons posi- tion paper, Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ), a relevant modification to the previous classification has been made and a new stage (0) added. The latter stage has been defined as “patients with no clinical evidence of necrotic bone, but who present with nonspecific symptoms or clinical and radiographic findings . . .” and the need for various clinical and radiologic aspects in defining this condi- tion was confirmed. .

Methylation of specific lysine residues in histone tails has been proposed to function as a stable epigenetic marker that directs biological functions altering chromatin structure. Recent findings have implicated alteration in heterochromatin formation as a contributing factor in cancer development. In order to verify whether changes in the overall level of H3K4 histone methylation could be involved in oral squamous carcinoma, the levels of H3K4me1, me2 and me3 were measured in oral squamous carcinoma, leukoplakias and normal tissues. The levels of H3K4me2 and me3 were significantly different in oral squamous cell carcinoma in comparison with normal tissue: the level of H3K4me2 was increased while that of H3K4me3 decreased. No significant differences could be found between the two types of tissues in the level of H3K4me1. A similar trend was found in the leukoplakias that appeared more like the pathological than normal tissue. These results support the idea that alteration of chromatin structure could contribute to oncogenic potential.

BackgroundThe aim of this paper was to determine the most common craniofacial changes in patients suffering Obstructive Sleep Apnea Syndrome (OSAS) with regards to the degree of obesity. Accordingly, cephalometric data reported in the literature was searched and analyzed.MethodsAfter a careful analysis of the literature from 1990 to 2006, 5 papers with similar procedural criteria were selected. Inclusion criteria were: recruitment of Caucasian patients with an apnea-hypopnea index (AHI) >10 as grouped in non-obese (Body Mass Index – [BMI] < 30)vs. obese (BMI ≥ 30).ResultsA low position of the hyoid bone was present in both groups. In non-obese patients, an increased value of the ANB angle and a reduced dimension of the cranial base (S-N) were found to be the most common finding, whereas major skeletal divergence (ANS-PNS ^Go-Me) was evident among obese patients. No strict association was found between OSAS and length of the soft palate.ConclusionIn both non-obese and obese OSAS patients, skeletal changes were often evident; with special emphasis of intermaxillary divergence in obese patients. Unexpectedly, in obese OSAS patients, alterations of oropharyngeal soft tissue were not always present and did not prevail.

Histone variants (e.g. H3) play an important role in chromatin structure and gene expression regulation of normal cells. Aims of this study were to: (1) estimate H3 and H3.3 histone mRNA expressions and their ratio in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL); (2) investigate whether H3 and H3.3 variants could play a role in the pathogenesis of OSCC and OL, also conditionally to HPV infection, age, gender, and main habits (tobacco smoking and alcohol drinking) in human beings studied. Twenty-three cases of OSCC and 20 cases of OL were examined in lesion site (LS) and juxtaposed clinically undamaged site (JUS) by RT-PCR for H3 and H3.3 histone mRNA; 13 healthy oral mucosa samples (HS) were investigated in a single site as controls. HPV DNA presence was investigated in the respective exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6). The data showed that both H3 and H3.3 histone mRNA crude concentrations are higher in OSCC (LS = 2901 +/- 459 ng of H3; JUS = 2699 +/- 658 ng of H3; LS = 3190 +/- 411 ng of H3.3; JUS = 2596 +/- 755 ng of H3.3) than those in OL (LS = 2095 +/- 349 ng of H3; JUS = 2192 +/- 897 ng of H3; LS = 2076 +/- 911 ng of H3.3; JUS = 1880 +/- 654 ng of H3.3) and in HS (2579 +/- 959 ng of H3; 2300 +/- 758 ng of H3.3), although not reaching any statistical significance. Interestingly, ratio of H3/H3.3 mRNA amounts decrease both in OSCC (0.99) and OL (1.009) vs HS (1.121). No association was found for H3 and H3.3 histone mRNA expressions in OSCC and OL with respect to HPV infection and the social-demographical variables considered (P > 0.2). The overall higher expression of H3.3 in damaged tissues up to the ratio inversion in OSCC especially in HPV+ alcohol drinkers (60.0%) represents the most interesting finding, in consideration of the proven ability of alcohol to act as permeability enhancer of human oral mucosa, to alter the mucosal structure and by this dynamics could favour the penetration through the epithelial layers of HPV.

We aimed to evaluate if in oral squamous cell carcinoma (OSCC) there is a relationship between histological grading (HG), TNM clinical stage and HPV infection; and to study the performance of fuzzy logic compared to traditional statistics, in the analysis of HPV status and correlates of OSCC. In cross-sectional analysis, the study group comprised 63 patients (mean age 68.89 years (SD ± 11.78), range (32–93); males 28 (44.4%), females 35 (55.6%)) with OSCC histologically diagnosed. HPV-DNA was studied in exfoliated oral epithelial cells by nested PCR (MY09/MY11 and GP5+/GP6+ primers). Data were analysed in parallel by traditional statistics with multivariate analysis and a fuzzy logic (FL) technique (membership functions as input, the ANFIS methodology, and the Sugeno’s model of first order). HPV infection was detected in 24/63 (38.1%) of OSCC, as being HPV+ve 14/36 (38.9%) in G1, 7/18 (38.9%) in G2, and 3/9 (33.3%) in G3; HPV+ve 8/33 (24.2%) in Stage I, 9/12 (75.0%) in Stage II, 6/11(54.5%) in Stage III, and 1/7 (14.3%) in Stage IV. In both methods of analysis, no significantly increased risk of HPV infection was found for any HG score; whereas, TNM stage II was significantly associated to HPV infection (p = 0.004; OR = 9.375 (95% CI = 2.030:43.30); OR0 = 11.148 (95% CI = 1.951:43.30)), and, in particular, to primary tumour size T2 (p = 0.0036; OR = 7.812 (95% CI = 1.914:31.890); OR0 = 9.414 (95% CI = 1.846:48.013)); FL (% of prevision: 79.8; Root MeanSquare Error (RMSE): 0.29). No association was found between HPV infection and any demographical variable. Our findings show an association between HPV infection with TNM (stage II – T2), but not with histological grading of OSCC. Also, FL seems to be an additional effective tool in analysing the relationship of HPV infection with correlates of OSCC. c 2005 Elsevier Ltd. All rights reserved.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family, which has been implicated in inhibition of apoptosis and control of mitotic progression. The finding that survivin is overexpressed in most human tumors but absent in normal adult tissues has led to the proposal of survivin as a promising therapeutic target for anticancer therapies. We decided to evaluate the effects of a ribozyme-based strategy for survivin inhibition in androgen-independent human prostate cancer cells. We constructed a Moloney-based retroviral vector expressing a ribozyme targeting the 3' end of the CUA(110) triplet in survivin mRNA, encoded as a chimeric RNA within adenoviral VA1 RNA. Polyclonal cell populations obtained by infection with the retroviral vector of two androgen-independent human prostate cancer cell lines (DU145 and PC-3) were selected for the study. Ribozyme-expressing prostate cancer cells were characterized by a significant reduction of survivin expression compared to parental cells transduced with a control ribozyme; the cells became polyploid, underwent caspase-9-dependent apoptosis and showed an altered pattern of gene expression, as detected by oligonucleotide array analysis. Survivin inhibition also increased the susceptibility of prostate cancer cells to cisplatin-induced apoptosis and prevented tumor formation when cells were xenografted in athymic nude mice. These findings suggest that manipulation of the antiapoptotic survivin pathway may provide a novel approach for the treatment of androgen-independent prostate cancer.

Endoscopic surgery may play an important role in most patients with pineal region tumors. We report our experience with 5 patients treated by a burr hole endoscopic technique. The procedure included in all cases third ventriculostomy for the correction of hydrocephalus, CSF sample for cytology and tumor markers, and tumor biopsy for histological diagnosis. Endoscopic biopsies showed a pineocytoma in two cases, a germinoma in 2 and a low-grade astrocytoma in one. We agree that endoscopic surgery may allow us to select cases requiring a microsurgical approach (medium-sized or large non-germ-cell tumors) from cases to be treated only by irradiation and chemotherapy (germinomas and other non-germ-cell tumors). Then, in some patients with pineal region tumors the endoscopic procedure remains the only surgical treatment. When a direct microsurgical approach is indicated, it may be performed in a non-emergency situation and after correction of the hydrocephalus by endoscopic third ventriculostomy.