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Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous malignancies presenting a wide range of pathological and clinical manifestations. Herein, we retrospectively characterize ten patients diagnosticated with LNEC, five of which were defined as well-moderately differentiated neuroendocrine carcinomas, and five that were defined as poorly differentiated neuroendocrine carcinomas, according to the latest WHO classification. Clinical features were analyzed and compared between the two subgroups together with a microRNA study which evidenced a peculiar signature likely related to poorly differentiated larynx neuroendocrine carcinomas. These findings may offer new useful insights for clinicians to improve diagnosis efficiency, therapy response, and patients’ outcome for this aggressive neoplasm.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.

Lymph node tuberculosis (TB) represents the most common form of extrapulmonary TB that affects most often laterocervical lymph nodes. The disease, favored by states of immunosuppression, manifests itself by usually unilateral swelling, which may be associated with skin changes (hyperaemia, infiltration or fistula) and poor systemic symptoms. Our study included 75 patients arrived at the hospital “V. Monaldi” of Naples from 2008 to 2012, in order to evaluate some aspects of clinical, diagnostic and therapeutic characteristics of tuberculous lymphadenopathy. All patients were subjected to clinical, microbiological and radiological findings, surgical biopsy (alternatively, fine needle aspiration cytology, FNAC) of lymph nodes affected by pathology, antituberculosis chemotherapy for six months and subsequent followup. 49% patients were female and 51% male (mean age 44.5 years). 50.7% of patients were immunocompromised (6.7% of HIV-positive cases, 4% with type II diabetes mellitus, 16% of drug users, 6.7% treated with immunosuppressive drugs, 4% affected by malnutrition, 12% homeless). The laterocervical lymphadenopathy was unilateral in 70.7% of cases, smaller than 2 cm in 66.7%, single in 62.7%, with normal overlying skin in 72%. 9.3% of cases showed pulmonary involvement. 68% of cases excisional biopsy was performed for microbiological and histopathological examination and in 32% patients FNAC (integrated with excisional biopsy in more than half of the cases). Lymph node tuberculosis is still a problem of high clinical significance. Diagnosis requires excisional biopsy for differential diagnosis from other forms of adenopathy; treatment utilises a multi-agent chemotherapy scheme that allows a good cure rate, with few side effects. © 2014 Bentham Science Publishers

Lipoma is a common benign tumor affecting the soft tissues arising in every location where fat is normally present. About 15% of lipomas occur in head and neck region. The lipoma of parotid gland is a rare entity, comprising 0.6% - 4.4% of all parotid tumors. The etiology remains unclear. The case described a lipoma of the superficial lobe of the parotid gland in a 46-year-old male.

Solitary intraparotid facial nerve plexiform neurofibromas are extremely rare. These tumors arise from Schwann cells. The plexiform variant is recognized by tortuous and multinodular gross and microscopic lesions. It has a high risk of malignant transformation. We report a case of a solitary plexiform neurofibroma in a 5-year-old Italian male, who initially presented a right parotid mass of four-month duration. He had not pain, trismus, facial weakness or previous trauma. There was not familiar history of Von Recklinghausen's disease. TC and MRI scans revealed a mass in the su- perficial lobe of the parotid gland. A partial parotidectomy was performed. Histopatological ex- amination indicated plexiform neurofibroma. The incidence, presentation, diagnosis and surgical treatment of this lesion are discussed. In our case, the tumor could be readily separated from the main trunk, and facial movement was completely preserved owing to the rich neural network around the mass.

Objectives: This study evaluates maintenance cetuximab administered every 2 weeks (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of patients with head and neck squamous cell cancer and compares the results with those obtained in a historical control group of patients receiving weekly cetuximab. Methods: After chemotherapy plus cetuximab as first-line treatment, in Group A, 36 patients enrolled from October 2016 to November 2017, received biweekly cetuximab, administered at 500 mg/m2. Group B was a control group of patients treated at our institution from August 2015 to September 2016 and received weekly infusion of cetuximab at 250 mg/m2. Results: Confirmed overall response rates were, respectively, 19% for Group A and 17% for Group B according to intention-to-treat analysis. During the maintenance treatment, median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B, respectively). The most common adverse events among treated subjects included fatigue, rash, and hypomagnesemia. Conclusion: Maintenance therapy with simplified biweekly cetuximab is a convenient, effective, and well-tolerated regimen in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Septoplasty is one of the most frequent surgical procedures performed by otolaryngologists. Despite successful surgical correction, many patients are not satisfied with their outcomes. So far, in clinical practice there is no consensus of opinion about the reliability of objective measurements of nasal patency and the correlation between objective measurements and subjective nasal patency symptoms. This study aims to assess the reasons for patient dissatisfaction after septoplasty and optimise pre-operative diagnostic management to predict surgical outcomes. We analysed 494 patients undergoing septoplasties with turbinoplasty by subjective Nasal Obstruction Symptom Evaluation questionnaire (NOSE) and objective active anterior rhinomanometric measurements before surgery and after 6 months. In our series, 17% had postoperative septal re-displacement; all patients had an anterior deviations at baseline. We found that the type of septal deviation, anterior vs posterior, was a significant predictor of postoperative functional improvement, whereas demographic characteristics as age, gender and smoke habit were not. Our data suggest that the anterior segment of the nasal septum was the most critical area for nasal airway resistance and more difficult to manage because it is likely to re-displace vs the posterior one and for this reason it represents a negative predictor of postoperative satisfaction.Settoplastica: è possibile identificare potenziali “predittori” di successo chirurgico?La settoplastica è una delle procedure chirurgiche più frequentemente eseguite in otorinolaringoiatria. In molti casi nonostante la correzione sia tecnicamente corretta, i pazienti non sono soddisfatti dei risultati ottenuti. Finora, nella pratica clinica non vi è consenso sull’affidabilità della diagnostica funzionale oggettiva, né sulla correlazione tra la misura oggettiva della pervietà nasale e i sintomi soggettivi riferiti dal paziente. Questo studio si propone di valutare le ragioni dell’insoddisfazione del paziente dopo settoplastica e di ottimizzare la gestione diagnostica pre-operatoria al fine di prevedere i risultati chirurgici. Abbiamo valutato 494 pazienti sottoposti a settoplastica con turbinoplastica con il questionario sulla valutazione dell’ ostruzione nasale, NOSE, e rinomanometria attiva anteriore. Le misurazioni sono state effettuate prima dell’intervento chirurgico e 6 mesi dopo. Nel 17% dei casi abbiamo osservato una re-dislocazione del setto, tutti i casi di redislocazione presentavano una deviazione anteriore preoperatoria. I nostri risultati suggeriscono che il tipo di deviazione del setto, anteriore vs posteriore, rappresenta un predittore statisticamente significativo del miglioramento funzionale postoperatorio, mentre le caratteristiche demografiche come età, sesso e abitudine al fumo, non lo sono. I dati ottenuti hanno, inoltre, dimostrato che relativamente alle resistenze nasali, l’area più critica e difficile da trattare è il segmento anteriore del setto poiché più a rischio di re-dislocazione rispetto al segmento posteriore, e per questo rappresenta un fattore predittivo negativo di soddisfazione post-operatoria.

The sense of smell, like taste and trigeminal senses, is a chemical sense dedicated to the perception of chemical stimulations and to the generation of responses to them. Although, from an evolutionary perspective, the chemical senses are the oldest of our senses, our knowledge on the neural processing of the three chemical senses is still incomplete and has been considerably lagging behind that of our other senses. The current review aims to give an overview about human smell function. In particular we focus on the anatomy and physiology of the olfactory system, the epidemiology and the causes of olfactory loss, and on the clinical management of olfactory disorders stressing the impact of smell loss on the quality of life. Lastly, we emphasize the importance of olfaction in every day life. In our opinion, the impairment of sense of smell should be taken into serious consideration by the clinicians, as it could be the indicator of important systemic diseases or the cause of domestic accidents.

Sudden sensorineural hearing loss is defined as an acute hearing reduction of 30 dB or more, in at least three consecutive frequencies, occurring within 3 days of symptom onset. There is no consensus on the best treatment option. The aims of this paper were to evaluate the effectiveness of a treatment protocol based on medical therapy combined with hyperbaric oxygen therapy and to examine the factors that influence the recovery of hearing (age, gender, the amount of time between the onset of symptoms and the initiation of treatment – time since onset –, audiometric curve type and objective vertigo). Audiometric results were evaluated according to Siegel’s criteria. In patients treated also with hyperbaric oxygen therapy we observed complete resolution in 44.1% of the patients, partial resolution in 37.2%, slight improvement in 10.5% and no improvement in 8.2% of the patients. This resolution pattern was significantly different from that observed in the patients treated only with medical therapy. The factors associated with a better prognosis were young age, rapid intervention, upward sloping or pantonal audiometric patterns and the absence of objective vertigo. Gender appeared to be an insignificant factor. Medical treatment associated with hyperbaric oxygen therapy gives better results in terms of hearing gain compared to exclusive medical treatment.

Early detection of laryngeal cancer, essential in the initial stages of the disease to achieve a high survival rate, is unfortunately hampered by the lack of specific symptoms. In this regard, there is a pressing need to dispose of reliable and non-invasive diagnostic and prognostic markers for a real time monitoring availing of accurate and reproducible methods, in order ensure applicability for early diagnosis and primary and secondary prevention. This review focuses on the recent reports that emphasize the crucial role of miRNAs in regulating laryngeal cancer tumorigenesis. In detail, we have reported the most characterized miRNAs with an established oncogenic or oncosuppressive role in cell biology of laryngeal cancer, also describing, for each of them, the main molecular mechanisms responsible for their specific function. We have also defined the potential of miRNAs as novel diagnostic and prognostic markers in virtue of their differential expression between laryngeal carcinoma tissues and the adjacent normal counterpart. Moreover, their proven stability in systemic circulation and other body fluids, as well as their easy detection and quantization, makes the analysis of miRNA signatures an excellent tool for clinicians as hallmark for cancer classification and diagnosis. Moreover, an eventual similarity between deregulated miRNAs in tumor tissues and in body fluids would allow to provide a considerable advantage for patients’ compliance, replacing invasive tissue biopsies with simple assays on easily obtained blood products.

BACKGROUND This study evaluates endoscopic and quality of life (QoL) outcomes in two groups, composed by both allergic (A) and non-allergic (N-A) adolescents undergoing septoplasty with concurrent turbinate surgery by radiofrequency treated after surgery with nasal spray containing liposomes and vitamins A and E. METHODS This double-blind randomized study was carried out on 40 patients (22 males, 18 females, mean age 15.5±1.0 years) undergoing septoplasty and volumetric tissue reduction of inferior turbinates by radiofrequency for post-traumatic deformities and severe nasal obstruction. We enrolled 20 subjects with positive skin prick tests and 20 with negative skin prick tests (SPT) to aeroallergens. All subjects underwent the Visual Analogue Scale (VAS) questionnaire and the nasal endoscopy score by Lund and Kennedy (LK) at baseline before surgery (T0) and 15 days (T15) and 21 days (T21) after treatment. After surgery, the nose was not packed and the day after surgery all subjects were randomized into two groups, experimental arm group I (GI) and control arm group II (GII) and given the treatment, nasal spray containing liposomes composed of phospholipids, fatty acids, and vitamin A and E for group I and saline solution (sodium chloride 0.9%) for group II. RESULTS After therapy, the VAS and LK scores were better (P

Adenoid cystic carcinoma (ACC) or 'cylindroma' is a malignant tumor that often occurs in the areas of the head and neck, affecting the secretory glands and the major and minor salivary glands. The present study describes a case of a patient who presented with a posterior tongue lesion. The case is of a 71-year-old female with an asymptomatic volume growth of the posterior left tongue perceived 8 months prior, and neoplastic cells positive for c-kit. A computed tomography of the head and neck showed asymmetry of the base of the tongue, which was enlarged in the left portion. A physical examination revealed a nodule on the posterior left tongue of ~3 cm in diameter, while the cervical lymph node chain had a normal size and consistency. Surgical exeresis of the tongue lesion and cervical lymph node dissection were performed. Subsequent to surgical removal of the cancer cells and adjuvant radiotherapy, the patient showed excellent health, although the follow-up remains in progress. ACC, one of the most biologically destructive tumors of the head and neck, is locally aggressive and gives rise to distant metastases. The tongue is the place of origin in 3.4-17.1% of cases. The treatment for ACC consists of primary surgical resection with adjuvant radiotherapy. To prevent the risk for distant metastasis, it is necessary to remove the first echelon nodes and monitor the patient with a long-term follow-up.

Malignant external otitis is a severe infection of the external auditoy canal, characterized by high gravity and mortality. It can arrive to skull base and originate intracranial complications. The most frequent pathogenic agent is Pseudomonas aeruginosa. Authors described two cases of external malignant otitis caused by Staphylococcus aureus, explaining clinical features, progression, diagnostic and therapeutic approach, prognosis of this disease. A comparison between Pseudomonas aeruginosa and Staphylococcus aureus malignant otitis was described, associated with a literature analysis.

Respiratory infections are the most frequent nosocomial infections after those urinaries and surgicals. We analysed respiratory infection incidences in patients treated with different kinds of respiratory assistance (non-invasive ventilation and invasive mechanical ventilation trough tracheostomy), studying 640 patients recovering in the intensive area of respiratory disease from 2010 to 2013. We had 113 cases of respiratory infections: 42.5% in patients of non-invasive ventilation group and 57.5% of patients treated with invasive ventilation with a statistically significant difference between the two groups. The patients treated with non-invasive ventilation showed a lower incidence of nosocomial respiratory infections. Prevention guidelines are important to reduce nosocomial infections frequency.

The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT.

Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed.

"Advanced head and neck squamous cell cancer (HNSCC) is currently treated with taxane-based chemotherapy. We have previously shown that docetaxel (DTX) induces a ras-dependent survival signal that can be antagonized by farnesyl transferase inhibitors (FTI) such as tipifarnib (TIP). Here we show that the synergistic TIP\/DTX combination determines synergistic apoptotic conditions but, at the same time, it modulates the expression of the components of the multichaperone complex that is, in turn, involved in the regulation of the stability of members of the ras-mediated pathway. Therefore, we have stably transfected HNSCC KB and Hep-2 cells with a plasmid encoding for HSP90. The expression of the protein was increased in both transfected cell lines but its activation status was increased in Hep-2 clones and decreased in KB clones. On the basis of these results, we have treated both parental and HSP90-transfected cells with a HSP90 inhibitor geldanamycin (GA). We have found that the antiproliferative activity of GA is dependent upon the activation status of HSP90 and that it is strongly synergistic when added in combination with TIP but not with DTX in cells overexpressing HSP90 and even more in cells with increased HSP90 activity. These data were paralleled by the decreased expression and activity of the components belonging to the ras→mediated signal transduction pathway. The present results suggest that multichaperone complex activation could be a resistance mechanism to the anti-proliferative and apoptotic effects induced by TIP and that the combination of FTIs such as TIP with GA could be a suitable therapeutic strategy in the treatment of HSP90-overexpressing HNSCC. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.. . " Advanced head and neck squamous cell cancer (HNSCC) is currently treated with taxane-based chemotherapy. We have previously shown that docetaxel (DTX) induces a ras-dependent survival signal that can be antagonized by farnesyl transferase inhibitors (FTI) such as tipifarnib (TIP). Here we show that the synergistic TIP/DTX combination determines synergistic apoptotic conditions but, at the same time, it modulates the expression of the components of the multichaperone complex that is, in turn, involved in the regulation of the stability of members of the ras-mediated pathway. Therefore, we have stably transfected HNSCC KB and Hep-2 cells with a plasmid encoding for HSP90. The expression of the protein was increased in both transfected cell lines but its activation status was increased in Hep-2 clones and decreased in KB clones. On the basis of these results, we have treated both parental and HSP90-transfected cells with a HSP90 inhibitor geldanamycin (GA). We have found that the antiproliferative activity of GA is dependent upon the activation status of HSP90 and that it is strongly synergistic when added in combination with TIP but not with DTX in cells overexpressing HSP90 and even more in cells with increased HSP90 activity. These data were paralleled by the decreased expression and activity of the components belonging to the ras→mediated signal transduction pathway. The present results suggest that multichaperone complex activation could be a resistance mechanism to the anti-proliferative and apoptotic effects induced by TIP and that the combination of FTIs such as TIP with GA could be a suitable therapeutic strategy in the treatment of HSP90-overexpressing HNSCC. © 2012 Wiley Periodicals, Inc.

Elderly patients with cancer are frequently undertreated as they are considered to be unfit for treatment due to inaccurate estimations of the operative risk. In the current study, the case of an 81-year-old female smoker with advanced breast cancer is presented. The patient had received numerous cycles of chemo- and hormonal therapy and the cancer only progressed locally. After six years, the patient developed a second type of cancer; a moderately differentiated squamous cell carcinoma of the tongue. The patient refused any local treatment and she received supportive care only. There is currently a lack of data regarding the molecular mechanisms of second primary cancers as well as other delayed outcomes following cancer treatment. Therefore, it is proposed that chemotherapy may promote the presentation of the second cancer as a result of immunosuppression.

Meningioma is a common intracranial tumor involving the meninges. The localization of this type of tumor is rarely extracranial due to its typically low invasive properties. Furthermore, invasion of the middle ear is exceptional. The present study reported a case of meningioma extending into the middle ear from the middle cranial fossa through the tegmen tympani. The clinical and pathological characteristics, as well as the outcome of the patient, were described.

Developments in surgical technique and, more importantly, the use of increasingly sophisticated biocompatible prostheses have meant that good results can be achieved for otosclerosis sufferers in terms of restored hearing and very little postsurgical discomfort. We set out to assess whether the diameter of the prostheses used for stapedotomy (platinum piston/polytetrafluoroethylene, i.e. Teflon) has any effect on surgical outcome. Two groups of otosclerotic patients were selected, and these underwent stapedotomy surgery during the second phase of the disease. A piston-Teflon type prosthesis was used, 5.50 mm in terms of length but of different diameters (group A: 0.4 mm; group B: 0.6 mm). All the patients underwent the same pure-tone audiometry test before surgery, and then at 1 week and 1 month after surgery, to assess function. We compared air conduction after surgery with bone conduction before surgery. The data collected was analysed using the χ2 (p < 0.05) test. This analysis showed that the results obtained with a 0.4-mm prosthesis or a 0.6-mm prosthesis are almost identical. There was no statistically significant difference in terms of hearing results when comparing either average tonal threshold or when analysing audiometric data frequency by frequency. It can be concluded, therefore, that in stapedotomy surgery, functional recovery is not affected by the diameter of the prosthesis used. A smaller diameter prosthesis is, however, the one of choice when the facial nerve is prominent or the oval window particularly narrow.

Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non-keratinized epithelium. K5 and K14 have been demonstrated in the mucosa and tumors of the oral cavity, oropharynx, hypopharynx and larynx, and in the mitotic active basal cells of a stratified squamous epithelium. The aim of the present study was to assess K5 expression in squamocellular carcinoma with various localizations in the head and neck. A total of 13 biopsy fragments were included from patients diagnosed with squamocellular carcinoma of the larynx area (n=2), pharynx (n=2), hard palate (n=1), tongue (n=2), submandibular (n=1), lip (n=1), gingival sulcus (n=1), nasal pyramid (n=1), maxilla (n=1) and zygomatic (n=1). The immunohistochemical staining for K5 was evaluated according to the following score criteria: 0 (0% positive cells); 1 (30% positive cells). K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well- and moderately-differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer.

Data from personal case histories, from 1984 to 2000 inclusive, are reported in order to contribute to a better understanding of some of the clinical and epidemiological ENT associated TB aspects. Analysis of these data shows that: 1. Like the pulmonary form, ENT localizations are increasing due to the traditional risk factors (immigration, poverty, immunodeficiency, drug addiction). 2. They are generally clinically primitive forms (which are found in extrapulmonary regions as the first expression of tubercular disease) and typically affect young people with a slight prevalence among females. Lymph gland localizations are the most frequent.

Viene descritto l'impiego del remifentanyl come tecnica anestesiologica innovativa nella terapia dell'otosclerosi

Lymph node metastases are responsible for shorter survival in oral squamous cell carcinoma (OSCC). The aim of the present study was to assess the node metastasis frequency and survival according to the node metastasis features in 121 neck dissections (NDs) performed for OSCC, identifying evidence-based correlations and contrasts with previous literature. The retrospective study involved 121 patients affected by OSCC who had undergone modified radical ND (MRND) for therapeutic, elective reasons or after intraoperative positivity to metastasis of sentinel lymph nodes (SLN+). Node metastasis frequency and behaviour (typical vs. atypical) and their number and distribution according to pre-surgical cTNM cancer staging were considered and overall survival Kaplan-Meier curves were calculated for each group in order to compare mortality according to ND type (elective, therapeutic, after SLN+), lymph node metastatic pattern (typical or atypical), size (micrometastasis vs. macrometastasis) and number. Results showed statistically significant different overall survival according to pre-surgical staging, number of lymph nodes harvested and intent to surgery. Sentinel lymph node resulted in the sole positive node affected by metastasis in small cT1- cT2/cN0 OSCC and an ND subsequent to its positivity during intraoperative assessment may be considered an overtreatment.

Data from personal case histories, from 1984 to 2000 inclusive, are reported in order to contribute to a better understanding of some of the clinical and epidemiological ENT associated TB aspects. Analysis of these data shows that: (1) Like the pulmonary form, ENT localizations are increasing due to the traditional risk factors (immigration, poverty, immunodeficiency, drug addiction). (2) They are generally clinically primitive forms (which are found in extrapulmonary regions as the first expression of tubercular disease) and typically affect young people with a slight prevalence among females. Lymph gland localizations are the most frequent.

The multi-drug combination of oxaliplatin (OXA), 5-Fluorouracil (5-FU) and leucovorin (LF) is currently considered as the gold standard treatment for metastatic colorectal carcinoma. In previous studies, we have studied a chemotherapy regimen containing gemcitabine (GEM), OXA, LF, and 5-FU (named GOLF regimen) that has shown a good safety profile and highly significant anti-tumor activity. In the present study, we have investigated on the anti-tumour mechanisms of GOLF in human colon cancer HT-29 and WiDr cell lines. We have found that GOLF induced growth inhibition that was largely caused by apoptosis differently from other combinations. Moreover, the different drugs composing GOLF were highly synergistic in inducing growth inhibition. Apoptosis induced by GOLF combination was paralleled by PARP cleavage and caspase 9 and 3 activation that were not recorded in the other combinations. An about 85% decrease of the activity of Erk and Akt was found in GOLF-treated cells. These effects were likely due to decreased expression of the upstream activator Raf-1 and of Akt itself, respectively. The intracellular levels of these signalling components can be post-translationally regulated by ubiquitin-dependent degradation through proteasome. Therefore, we have evaluated the expression of some chaperone components and we have found that GOLF did not affect the expression of both heat shock protein (HSP) 90 and 27 but induced an about 90% increase of HSP70 levels suggesting the inactivation of the multi-chaperone complex. Moreover, an about 4-fold increase of the ubiquitination of Raf-1 was also found and the addition for 12 h of 10 microM proteasome inhibitor lactacystin caused an accumulation of the ubiquitinated isoforms of Raf-1. In conclusions, GOLF was a combination highly synergistic in inducing both growth inhibition and apoptosis of colon cancer cells. These effects likely occurred through the disruption of critical survival pathways and the inactivation of multi-chaperone complex.

Anomalous proliferation of the cholesteatoma epithelium is caused by extrinsic factors such as toxins or bacterial antigens combined with lytic enzymes, lymphokines and cytokines released from the inflammatory infiltrate. This could explain the close relationship between the aggressiveness of cholesteatoma and repeated bacterial superinfection, therefore it is very important to know the bacteria involved in order to control the regrowth of skin following surgery, reduce the aggressive potential of the cholesteatoma and limit the incidence of complications. This study focused on 70 females and 80 males aged between 15 and 65 years, affected by cholesteatomatous otitis media; all underwent bacteriological examination of the auricular secretion. The floral bacteria which proved to play the most important role (60.3%) were the aerobic type and the highest levels were those of Pseudomonas aeruginosa (31.1%) followed by Staphylococcus aureus (19.1%), Proteus mirabilis (7.7%), Escherichia coli (1.4%) and Klebsiella pneumoniae (1%). Anaerobic floral bacteria were found in a fairly high percentage of cases (38.2%); in particular, anaerobic gram-positive cocci (Peptococcus 12.4% and Peptostreptococcus in 4.8% of cases), Bacteroides (12.4%), Clostridium (3.8%), Fusobacterium (2.9%) and Propionobacterium (1.9%) were isolated. In 3 cases of mycetes (1.4%) only Aspergillus, in association with Pseudomonas and Staphylococcus, was identified. The study showed, then, how effective second generation fluoroquinolones and third generation cephalosporins are (the latter being used in pre-adolescent children), the reason being that these antibiotics work not only on Pseudomonas and Staphylococcus, but also on the anaerobic bacteria.