Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8+ T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8+ T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy

Treatment of iatrogenic submandibular sialocele with botulinum toxin : case report

We report the case of a 40-year-old woman with a submandibular sialocele (diagnosed by ultrasonography and magnetic resonance sialography) after sialoadenectomy for sialolithiasis. Type A botulinum toxin was injected percutaneously under colour Doppler ultrasonographic guidance into the sialocele and the residual salivary gland. Five months later the submandibular swelling had gone, and we gave a second injection of botulinum toxin to block any residual secretory activity. There were no side effects. This is, as far as we know, the first published report of the use of botulinum toxin to treat an iatrogenic submandibular sialocele

Association between methylenetetrahydrofolate reductase polymorphisms, alcohol intake and oropharyngolaryngeal carcinoma in northern Italy

Folate metabolism dysregulation may lead to abnormal cell proliferation and predispose to carcinogenesis by inducing DNA hypomethylation. Folate pathways may be modified by polymorphisms in relevant genes, such as that for methylenetetrahydrofolate reductase (MTHFR), or by alcohol consumption. We investigated the relationship between MTHFR mutations at nucleotides C677T and A1298C, which cause reduced MTHFR enzyme activity, and susceptibility to oropharyngolaryngeal carcinoma in 65 patients and 100 controls. We isolated DNA from peripheral blood leukocytes. In oropharyngolaryngeal carcinoma cases the C677T heterozygous genotype was more frequent (p = 0.018), the allele frequency of MTHFR 677T was greater (p = 0.019) and the genotype 677TT/1298AA was more frequent (p = 0.001). A higher risk of carcinoma was found in the case of moderate drinkers with mutant MTHFR homozygosis or double heterozygosis (OR = 21.2 and OR = 9.1, respectively; p trend = 0.002), and the association was maintained for the different cancer sites (glottic, supraglottic, oropharyngeal). Our findings support the hypothesis that the interaction of alcohol intake and MTHFR polymorphisms might contribute to susceptibility to carcinogenesis of the oropharyngolaryngeal tract

Long-term vocal functional results after glottectomy: a multi-dimensional analysis

Horizontal glottectomy (HG) is an efficient surgical procedure for the treatment of selected laryngeal carcinoma. The aim of this study was to verify the long-term voice results in a group of HG subjects. The study involved 16 subjects who had undergone HG at least 1 year before. Each subject underwent laryngoscopy and his/her voice was perceptually rated using the GRBAS (grade, roughness, breathiness, asthenicity, strain) scale; the other objective examinations included maximum phonation time (MPT), spectrography, and perturbation analysis. Finally, all of the subjects assessed their own voice using the voice handicap index (VHI). The endoscopic examinations showed good arytenoid mobility and antero-posterior valving of the arytenoid-epiglottal- ventricular band complex, whereas vibration of the neoglottis was more severely impaired. The mean GRBAS values were, respectively, 2.7, 1.9, 1.9, 0.9 and 0.7; the mean MPT was 8.2 s. The Yanagihara score of the voice spectrograms was 4 in all cases; perturbation analysis revealed the following mean values: fundamental frequency = 147; Jitter% = 6.5; Shimmer% = 13.9; and noise-to-harmonic ratio = 0.76. The mean VHI value was 35.8. Objective and subjective data showed a dysphonic voice after HG, whereas the self-assessment results revealed a low degree of perceived disability, suggesting that oral communication was well preserved

Prothrombotic gene mutations in patients with sudden sensorineural hearing loss and cardiovascular thrombotic

Objectives: Impaired cochlear perfusion seems to be an important event in sudden sensorineural heading loss. Prothrombotic gene mutations have been related to vascular disorders and sudden hearing loss. We assessed the prothrombotic risk in 10 patients with sudden sensorineural hearing loss who had previously experienced cardiovascular events to support its vascular pathogenesis. Methods: Ten patients underwent hematologic tests (MTHER C677T/A1298C, prothrombin G20210A, platelet were compared with those of 100 previously investigated patients With Sudden hearing loss alone and those of 200 healthy controls. DNA was isolated from peripheral blood leukocytes, and the gene mutations were investigated by polymerase chain reaction and a LightCycler DNA analyzer. Results: Two patient had 2 mutant alleles, 6 had 3, and 2 had 4. The mean homocysteine, cholesterol, and fibrinogen levels were above the Upper limit of normal; the mean folate levels were slightly above the lower limit of normal. Multiple mutations were more frequent in the patient group than in the previously analyzed patients and healthy controls. Conclusions: The association between inherited and acquired prothrombotic factors ill Patients With sudden sensorineural hearing loss and thrombotic diseases in other sitcs that a multifactorial mechanism may underlic microvascular cochlear impairment. Hematologic investigation, including MTHFR, prothrornbin, platelet,and V Leiden genotyping, may help to detect patients at potential risk of recurrent hearing loss and Multiple microvascular diseases. and could be usefully performed in otherwise idiopathic Sudden sensorineural hearing loss

Comparative ultrasonographic, magnetic resonance sialographic, and videoendoscopic assessment of salivary duct disorders

Objectives: Salivary duct disorders are the second most common cause of obstruction after calculi. Magnetic resonance sialography has been recently proposed as a means of diagnosing a heterogeneous group of salivary disorders, and so we compared it with sialoendoscopy in evaluating stenoses and sialectasia in 24 patients with obstructive symptoms and ultrasonographic results negative for calculi or masses. Methods: All of the patients (19 of whom had recurrent unilateral or bilateral swollen parotid glands and 5 of whom also had recurrent swollen submandibular glands) underwent dynamic color Doppler ultrasonography and dynamic magnetic resonance sialography with lemon juice stimulation of saliva; 18 patients also underwent diagnostic sialoendoscopy. Results: Ultrasonography and color Doppler ultrasonography showed duct dilatation in all patients (bilateral in 5 with parotid stenosis). Magnetic resonance sialography confirmed duct dilatation and stenosis in all of the patients, and revealed the simultaneous presence of calculi in 4 cases. A parotid sialocele was found in 4 cases. The magnetic resonance sialographic findings were confirmed in the patients who underwent sialoendoscopy. No side effects were observed. Conclusions: Magnetic resonance sialography following prediagnostic ultrasonography allows an adequate diagnosis of salivary duct disorders such as stenosis and sialectasia, as confirmed by objective sialoendoscopic assessment. Magnetic resonance sialography also makes it possible to visualize the salivary duct system up to its tertiary branches and, in this regard, may be considered a valid, noninvasive method for the evaluation of salivary duct disorders

Comparative ultrasonographic, magnetic resonance sialographic, and videoendoscopic assessment of salivary duct disorders

Objectives: Salivary duct disorders are the second most common cause of obstruction after calculi. Magnetic resonance sialography has been recently proposed as a means of diagnosing a heterogeneous group of salivary disorders, and so we compared it with sialoendoscopy in evaluating stenoses and sialectasia in 24 patients with obstructive symptoms and ultrasonographic results negative for calculi or masses. Methods: All of the patients (19 of whom had recurrent unilateral or bilateral swollen parotid glands and 5 of whom also had recurrent swollen submandibular glands) underwent dynamic color Doppler ultrasonography and dynamic magnetic resonance sialography with lemon juice stimulation of saliva; 18 patients also underwent diagnostic sialoendoscopy. Results: Ultrasonography and color Doppler ultrasonography showed duct dilatation in all patients (bilateral in 5 with parotid stenosis). Magnetic resonance sialography confirmed duct dilatation and stenosis in all of the patients, and revealed the simultaneous presence of calculi in 4 cases. A parotid sialocele was found in 4 cases. The magnetic resonance sialographic findings were confirmed in the patients who underwent sialoendoscopy. No side effects were observed. Conclusions: Magnetic resonance sialography following prediagnostic ultrasonography allows an adequate diagnosis of salivary duct disorders such as stenosis and sialectasia, as confirmed by objective sialoendoscopic assessment. Magnetic resonance sialography also makes it possible to visualize the salivary duct system up to its tertiary branches and, in this regard, may be considered a valid, noninvasive method for the evaluation of salivary duct disorders

Surgery and topic cidofovir for nasal squamous papillomatosis in HIV+ patient

Intranasal schneiderian exophytic squamous papillomatosis is rare and often secondary to human papilloma virus infection. Treatment usually consists of repeated surgical or endoscopic excisions due to recurrences. The use of intravenous or intralesional or topically applied cidofovir, a cytidine nucleotide analogue suppressing viral replication, alone or as adjuvant therapy has been proposed and described in the literature for the treatment of other human papillomavirus (HPV)-related lesions. We firstly describe a successful combined approach of surgery and topical cidofovir for recurrent nasal HPV-related exophytic squamous papillomatosis in a HIV-infected patient. As no untoward effects were encountered this therapeutical option should be considered in the management of recurrent nasal papillomatosis in HIV-infected patients

Genetic and acquired prothrombotic risk factors and sudden hearing loss

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a frequently encountered condition, and various pathogenetic mechanisms have been hypothesized, such as viral infections, autoimmune processes, and ischemic events; however, whatever the cause, impaired cochlear perfusion appears to be the most important event. A number of inherited prothrombotic risk factors and their related genetic alterations have recently been correlated with vascular disorders. METHODS: To investigate the mechanisms of vascular thrombosis of the inner ear leading to sudden HL, we examined 100 patients with SSNHL for the presence of acquired or inherited prothrombotic risk factors and 200 healthy volunteers as controls. All of the subjects underwent hematologic examinations, including MTHFR C677T and A1298C, prothrombin G20210A, platelet GlyIIIaA1/A2, V Leiden G1691A genotyping, fibrinogenemia, cholesterolemia, homocystinemia, and folatemia. Genomic DNA was isolated from peripheral blood leukocytes using standard methods, and gene mutations were investigated using a LightCycler DNA analyser and polymerase chain reaction. RESULTS: A statistically significant association was found between SSNHL and the MTHFR C677T/A1298C polymorphisms, the prothrombin G20210A transition, and the platelet GlyIIIa and V Leiden G1691A mutations. Furthermore, the SSNHL patients had significantly higher levels of fibrinogenemia, cholesterolemia, and homocystinemia and lower levels of folatemia than the controls (P < .0001). CONCLUSIONS: The association between inherited and acquired prothrombotic factors and sudden HL suggests that the microvascular impairment causing SSNHL may be caused by a multifactorial mechanism. All patients with ISSNHL should undergo a comprehensive hematologic investigation of inherited and acquired prothrombotic factors, including MTHFR polymorphisms, the prothrombin transition, and the platelet and V Leiden mutations, to identify a subset of patients at high risk of recurrent HL