Pedicled palatal flap for surgical repair of oro-nasal fistula.

Oronasal fistula can occur secondary to various pathologies, but cleft surgery is the most common. The authors propose a pedicled palatal flap technique for surgical repair of small oronasal fistula (0.5-0.8 cm), derived from their experience in the treatment of 7 patients between March 2003 and December 2007. In one case, the fistula was induced by prolonged snorting of cocaine. In the other cases, the fistulas developed after excision of a benign tumor of the palate. For the cocaine-induced fistula, failure of the repair attempt was apparent within 7 days of surgery. In all other cases, complete fistula closure was obtained, and no complications occurred.

Mechanism of action of trabectedin in desmoplastic small round cell tumor cells.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. Current treatments are not very effective so new active drugs are needed. Trabectedin, now used as a single agent for the treatment of soft tissue sarcoma, was reported to be active in some pre-treated DSRCT patients. Using JN-DSRCT-1, a cell line derived from DSRCT expressing the EWS-WT1 fusion protein, we investigated the ability of trabectedin to modify the function of the chimeric protein, as in other sarcomas expressing fusion proteins. After detailed characterization of the EWS-WT1 transcripts structure, we investigated the mode of action of trabectedin, looking at the expression and function of the oncogenic chimera. METHODS: We characterized JN-DSRCT-1 cells using cellular approaches (FISH, Clonogenicity assay) and molecular approaches (Sanger sequencing, ChIP, GEP). RESULTS: JN-DSRCT-1 cells were sensitive to trabectedin at nanomolar concentrations. The cell line expresses different variants of EWS-WT1, some already identified in patients. EWS-WT1 mRNA expression was affected by trabectedin and chimeric protein binding on its target gene promoters was reduced. Expression profiling indicated that trabectedin affects the expression of genes involved in cell proliferation and apoptosis. CONCLUSIONS: The JN-DSRCT-1 cell line, in vitro, is sensitive to trabectedin: after drug exposure, EWS-WT1 chimera expression decreases as well as binding on its target promoters. Probably the heterogeneity of chimera transcripts is an obstacle to precisely defining the molecular mode of action of drugs, calling for further cellular models of DSRCT, possibly growing in vivo too, to mimic the biological complexity of this disease.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI-TOF/MS.

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.

Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. METHODS: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. RESULTS: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. CONCLUSION: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

Surgical treatment of sacral chordoma: survival and prognostic factors.

INTRODUCTION: Sacral chordoma is a rare low-to-intermediate grade malignant tumour. The mainstay of treatment is still surgery with en bloc and wide resection margins, which can grant the best chances of a long-term control or cure of this disease. The first aim of this paper is to collect data about survival, time to local recurrence and metastasis among patients affected by sacral chordoma and primarily treated with surgery. The second aim is to analyze the influence of level resection, tumor volume and surgical margins on local recurrence. MATERIALS AND METHODS: The study population was composed of 14 patients treated with sacral chordoma resection at the National Tumour Institute of Naples-Pascale (Italy) from January 2000 to June 2013. The median follow-up was 84 months (range 24-132 months). The follow-up was characterized by: standard radiographs, MRI, and a CT scan of the chest annually. Time to recurrence or metastasis was calculated from the date of resection to the date of diagnosis of first recurrence or metastasis. RESULTS: Out of all the patients, six died (42.86 %) during the follow-up; 6 (42.86 %) had local recurrence; 4 (28.57 %) had metastasis. At univariate analysis wide surgical margins (R0) were associated with increased survival up to a local recurrence (OR = 0.0286; 95 % CI = 0.0014-0.5739; P = 0.026); the level of resection (OR = 3.33; 95 % CI = 0.3619-30.7025; P = 0.592) and tumour volume (P = 1) did not show a statistically significant correlation. DISCUSSION: Based on our experience, we hope all patients to be treated by surgery, the only good standard treatment of this disease. The resection should result in margins as wide as possible. For these reasons, it is essential for this disease to be treated in highly specialized centres because only a complete surgery can offer a chance to care for these patients. CONCLUSIONS: Solid survival at long-term follow-up can be achieved by a surgical resection performed with wide margins.

Immunohistochemical correlation between microvessel density and lymphoid infiltrate in radicular cysts.

OBJECTIVE: Radicular cysts occur as a result of the immunological response to continuous antigenic stimulation from root canals. We correlated the immunophenotypical composition of the lymphoid infiltrate to the microvessel density expressed by the count of CD34 reactive endothelial cells in radicular cysts. SUBJECTS AND METHODS: Thirty-four cases of radicular cysts were evaluated by immunohistochemistry, using antibodies against B- and T-cell antigens (CD20, CD3, CD4, CD8) and against the endothelial cell marker CD34. Statistical analysis was performed. RESULTS: In the epithelium, we observed a low amount of lymphoid infiltrate in all 34 radicular cysts, and a strong significant negative correlation between T and B lymphocytes and between T-helper and T-cytotoxic/suppressor lymphocytes. In the cyst capsule, we observed a significant positive correlation between B and T lymphocytes, B and T-cytotoxic/suppressor lymphocytes, T and T-helper lymphocytes and between the number of CD34+ blood vessels and T and T-helper lymphocytes, respectively. We observed a statistically significant correlation between percentage of CD34+ vessels and inflammatory infiltrate grade. CONCLUSIONS: Both humoral and cellular immune reactions and neovascularization are likely to occur in the complex events of tissue destruction. The inflammatory infiltrate has an important role in neoangiogenesis and consequently in radicular cysts development and growth.

Importance of spinal deformity index in risk evaluation of VCF (vertebral compression fractures) in obese subjects: prospective study.

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.

Dynamic evaluation of benign neoplasm of parotid glands with multidetector row CT.

AIM: The aim of this paper was to evaluate the role of net-enhancement (NE) of benign salivary glands with multiphase multidetector row CT (MDCT). METHODS: Forty-eight patients (M=27, F=21), aged 35-76 years old (mean =57) with benign parotid neoplasms were examinated with 4 MDCT, at 20'', 40'', 70'' e 9' after intravenous administration of contrast medium. NE was calculated after subtracting precontrast phase to postcontrast phases. Final data were compared to the histopathology. RESULTS: Thirty-six cases were pleomorphic adenomas (PA), 24 Warthin (WT). PA had a medium NE values of 23 HU, 74 HU, 53 HU e 34 HU at 20'', 40'', 70'' e 9' respectively. WT had a medium NE of 52 HU, 54 HU, 40 HU e 39 HU respectively at the same times. After subtracting precontrast phase to the delayed phase, with NE at 9' and cut-off of 34 HU, we have differenziate PA from WT and normal gland with specifity (SP) 87%, sensibility (SE) 60%, positive predictive value (PPV) and negative predictive value (NPV) of 75% and 59%; with NE at 20'' and cut-off of 54HU we have distingueshed WT from AP with SP 83%, SE 50%, PPV 75% and NPV 63%. CONCLUSION: The study of NE can allow the characterization of benign parotid gland tumors.

Molecular insights into the effects of sodium hyaluronate preparations in keratinocytes.

BACKGROUND: Hyaluronic acid (HA) preparations are widely used in clinical practice to accelerate wound healing, but it is not clear whether HA can exert direct effects on epidermal keratinocytes. AIM: To investigate the molecular and functional changes induced by HA preparations in keratinocytes by measuring global gene expression and wound healing. METHODS: Human skin keratinocytes were used for this study. They were treated with either sodium hyaluronate (SH) alone or a commercial adjuvant gel (Aminogam(®)) containing SH in combination with a pool of synthetic amino acids (L-proline, L-leucine, L-lysine and glycine). Global gene expression of nearly 55,000 transcripts was investigated with a chip array (Affymetrix Human Genome U133 2.0 Plus). RESULTS: We found that keratinocytes expressed all major HA receptors at the transcriptional level. In a fibroblast-free system, both SH and the adjuvant gel could effectively promote wound healing of keratinocytes. Major gene expression changes induced by HA preparations involves proteolysis, proteinase inhibitors, cellular metabolism and cytoskeleton. In total, 21 genes were differentially transcribed by SH and the adjuvant gel. CONCLUSIONS: Keratinocytes represent a previously underestimated target for HA action in wound healing. HA preparations induce transcriptional changes in keratinocytes and stimulate wound closure. Furthermore, the addition of synthetic amino acids to SH induces a distinct transcriptional profile.

Expression of sexual hormones receptors in oral squamous cell carcinoma.

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<0.05 were considered statistically significant. AR transcripts were less expressed in OSCC specimens than in healthy tissues, while levels of ERα transcripts significantly increased in tumor samples. These preliminary data show different expression patterns of AR and ERα mRNAs in malignant tissues of oral mucosa and could suggest an involvement of these sexual hormones in oral cancer.

Expression of ß-catenin and γ-catenin in maxillary bone regeneration.

ß- and γ-catenin are components of catenin family involved in cadherin adhesion function. Recently it has been shown that this family is involved in other functions such as signaling and activation of transcription factors. The final goal of this study was to evaluate the role of ß- and γ-catenin in bone cell physiology and bone regeneration. Formalin-fixed-paraffin embedded specimens of 15 human bone specimens after sinus lift were collected and examined by immunohistochemstry using primary antibodies against ß- and γ-catenin. Staining intensity and cellular localization were evaluated. ß and γ-catenin showed a very high level of expression in human bone tissues. In particular catenins were expressed in cells with morphological findings of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid matrix and bone. Osteoclasts showed also positivity for catenins. Osteocytes, cells located in lacunae of mature mineralized bone with function of bone vitality maintenance, showed no expression for catenins. Specimens characterized by high amount of catenins in osteoblasts at 1° month showed high grade of bone maturation at 3° month. Data demonstrated an overall involvement of catenins in human bone tissues and in particular during bone regeneration process. The presence of staining for ß- and γ-catenin particularly in osteoblasts demonstrates a significant role of catenins in functions, other than in cadherin interaction, such as signaling and activation of transcription factors during differentiation of bone tissues.

Efficacy of a spray compound containing a pool of collagen precursor synthetic aminoacids (l-proline, l-leucine, l-lysine and glycine) combined with sodium hyaluronate to manage chemo/radiotherapy-induced oral mucositis: preliminary data of an open trial.

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 manufacturers instructions. At time T0 (baseline before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0100) 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 less than 0.0001; z=-4.541). A progressive reduction of pain through the 2 weeks was also noted (p less than 0.0001). Patient lesions treated with SH-Asbased spray also significantly improved after 72 hours of treatment (p=0.0051; z=-2.803). During the two-week observation, all patients significantly improved from the baseline (p less than 0.0001) and progressively ameliorated their ability to swallow foods and liquids. The compliance of all patients to the product was very good, and at the end of the study there were no adverse effects. The results suggest that the SHAAs-based spray accelerates lesion healing and above all helps to manage mucositis pain, especially in terms of immediate pain relief (after 2 hours from application). Although further randomized controlled studies are recommended, our findings suggest that frequent applications of this spray may offer rapid and effective pain management, aiding faster mucosal wound healing.

Warthin's tumor distribution within the parotid gland. A feasible etiologic source from lymph nodal tissue.

AIM: Warthin's tumor (WT) is the second commonest parotid gland neoplasm after pleomorphic adenoma (PA). It mainly arises from the lower pole of the superficial parotid lobe (i.e., tail of gland), a site with the greatest distribution of intra-parotid lymph nodes, and its definitive etiopathogenesis is still unclear. The aim of this study was to support the strict topic and etiologic link hypothesised between this tumor and the intraparotid lymph nodes, as being massively present in the tail, by assessing the WT distribution within the parotid gland. METHODS: Seventy-one WTs excised from 64 patients were compared retrospectively with 134 PAs from 133 patients, as controls. In all sample, staging of parotid gland tumors was defined by sonography and magnetic resonance imaging. Furthermore, tumor localization, size, bilaterality and multifocality were assessed according to radiological, intraoperative and histopathological findings. RESULTS: WTs were mainly detected in the tail (73%), less in the superficial lobe (23%) and the deep one (4%). WT presented with bilateral and synchronous lesions in 10% of cases vs. 0.75% of controls. CONCLUSION: Since the tail has been well known to present the greatest distribution of intra-parotid lymph nodes, our clinical findings on WT parotid localization could suggest the possible origin of this tumor from epithelial salivary gland ductal inclusions, as being likely entrapped during embryogenesis within the intra-parotid lymph nodes, and could support the hypothesis of a heterotopy in the pathogenesis of WT. However, this suggestive hypothesis based only on clinical and "topographic" data should be confirmed by histopathological studies about the presence of the salivary ductal elements trapped within the intra-parotid lymph nodes.

Oral candidiasis: a comparison between conventional methods and multiplex polymerase chain reaction for species identification.

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.

Squamous cell carcinoma arising from long-term (50-year) Lupus vulgaris: is there a need for a close medical follow-up in such chronic diseases?

Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are represented by miliary tuberculosis of the skin, tuberculous chancre, scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and lupus vulgaris (LV). Among this group, LV is the most common skin condition, diagnosed in 10% of tuberculotic patients. The authors report herein a case of squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and underline the need of an extensive follow-up of tuberculotic lesions.

Eccrine hidrocystoma: a neoformation to be considered in differential diagnoses of facial swellings.

Hidrocystomas are relatively rare cystic skin tumors. The precise histogenetic derivation and the cellular differentiation of these tumors has been largely debated. Usually, the mean age at diagnosis of the patients with eccrine hidrocystomas (EH) is 51.6 years, 54.0 years for females and 32.5 years for males. EH develop predominantly in females (sex ratio 1:6.5). Most patients are asymptomatic; predilection sites are the lower eyelids, nose and lateral canthus. The authors report a rare case of EH of the lower face in a 57-year-old Caucasian male patient presented with mandibular asymmetry due to an asymptomatic neoformation on the left mandibular region. The present report is relevant for the clinical differential diagnoses that a submandibular lesion requires, to exclude neoplasms of osteogenic, mesenchymal, epithelial, vascular or glandular origin. In the case described the histopathological findings, characterized by the presence of partially collapsed, unilocular cyst lined by small, monomoprhous cuboidal epithelial cells with eosinophilic cytoplasm and a highly vascular, slightly edematous stroma, suggested the diagnosis of EH. The standard treatments for EH is surgical excision, which is associated with a high cure rate and a low recurrence rate. In conclusion, in case of EH in the submandibular region, a specific clinical and instrumental diagnosis is very difficult to make, and histopathological diagnosis represents the standard diagnostic procedure.

Chondroid syringoma: a rare tumor of orofacial region.

Chondroid syringoma is a rare tumor arising from the major and minor salivary glands. The incidence of chondroid syringoma is reported to be <0.01% among the primary skin tumors. Eighty percent of the chondroid syringomas are seen in older patients , commonly on head and neck region and mostly on the cheek and nose. The authors report a case discussing the surgical management of a chondroid syringoma and pointing out the importance of including this tumor in the differential diagnosis of small subcutaneous nodules in the head and neck region, in middle-age male patients.