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There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Interventional sialendoscopy has become the predominant therapeutic procedure for the management of obstructive salivary disorders, but only a few multicentre studies of large series of patients with a long-term follow-up have been published. This Italian multicentre study involved 1152 patients (553 females; mean age 50 years) who, after at least a clinical and ultrasonographic evaluation, underwent a total of 1342 diagnostic and interventional sialendoscopies, 44.6% of which involved the parotid gland. 12% (n = 138) of patients underwent multiple treatments. The procedure was successful in 1309 cases. In 33 cases (2.4%) the procedure could not be concluded mainly because of complete duct stenosis (21 cases). Salivary stones were the main cause of obstruction (55%), followed by ductal stenosis and anomalies (16%), mucous plugs (14.5%) and sialodochitis (4.7%). Complete therapeutic success was obtained in 92.5% of patients after one or more procedures, and was ineffective in < 8%. Untoward effects (peri and postoperative complications) were observed in 5.4% of cases. Sialendoscopy proved to be an effective, valid and safe procedure in the diagnostic and therapeutic management of non-neoplastic obstructive salivary gland diseases.

Intraoperative nerve monitoring (IONM) aimed at reducing the injuries of recurrent laryngeal nerve during thyroidectomy is controversial. We conducted a meta-analysis to assess the incidence of nerve injuries with or without IONM. Studies published from January 1994 to February 2012 in English language on humans were identified. Heterogeneity of studies was checked by the Higgins test. Summary estimates of predictive values of injury were made using the Mantel-Haenszel test based on the fixed-effects model. Publication bias was assessed by a funnel plot and Egger’s method. Eight articles were selected accounting a total of 5257 nerves at risk. IONM revealed a significant impact in preventing transient injuries (positive predictive value = 5% [95% CI: 2-8], negative = 96% [95% CI: 91-100], relative risk = 0.73 [95% CI: 0.54-0.98], p = 0.035), whereas they failed to demonstrate effect on permanent injuries (positive predictive value = 2% [95% CI: 0.6-3.8], negative 99% [95% CI: 97-100], relative risk = 0.73 [95% CI: 0.44-1.23], p = 0.235). This meta-analysis demonstrated the merit of IONM in preventing transient injury during thyroidectomy. No advantage was found in permanent injuries.

Objectives-The purpose of this report is to describe an example of angiosarcoma (AS) of the submandibular salivary gland. The clinical and immunohistopathologic features of these lesions are also reviewed.Material and Methods-A 17-year-old male high school student was admitted to our clinic with a 1-year history of a slow growing, tender mass in the left submandibular region. Physical examination on initial presentation revealed a diffuse soft tissue mass 6 cm in diameter involving the left submandibular region. MRI analysis revealed a mass located superolateral to the submandibular salivary gland, measuring 4.0 x 2.0 cm(2). The mass was excised completely together with the left submandibular salivary gland. Histopathologic analysis led to a diagnosis of AS. Immunohistochemical studies were also used to determine endothelial cell differentiation. Owing to the lateralized nature of the lesion, a left functional neck dissection was performed and postoperative radiotherapy was planned.Results-AS is a malignant tumor of endothelial cell origin that may occur in any region of the body. The commonest sites include the extremities and the retroperitoneal space, with only 4% of AS tumors arising in the head and neck area. The submandibular salivary gland is an extremely rare location for this tumor. Based on a literature review, this case report represents only the second reported case of AS of the submandibular salivary gland.Conclusions-In most cases, radical surgery and postoperative radiotherapy are advocated to treat patients with AS tumors, with lymph node clearance recommended in cases of lateralized lesions. In some patients, distant metastasis may occur after many years, which necessitates long-term follow-up. The prognosis is poor in most cases of AS.

In order to verify whether anti-endothelial cell autoantibodies (AECAs) can be used as serological markers of inner ear vasculitis in sudden sensorineural hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated. All patients underwent a routine general physical examination and extensive audiovestibular, microbiological and immunological investigations. Fourteen normal subjects without a history of HL, autoimmune or metabolic disease served as controls. Detection of AECAs was performed using an indirect immunofluorescence technique. AECA-positive patients were treated with methylprednisone, while AECA-negative patients were treated with a combined regimen of steroids, plasma expander and aspirin. The average hearing recovery for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after treatment and every 3 months thereafter; median follow-up was 12 months (range 9-18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were AECA-positive and thus differed significantly from the normal population in whom only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was associated with being AECA-positive in 8/11 cases. During follow-up, 25/32 patients improved their hearing and 17 of these patients were AECA-negative. The seven cases without hearing improvement were all AECA-positive. In patients with SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may represent a serological marker of vasculitis even if they are not inner ear-specific and even if they represent an epi-phenomenon rather than the only cause of SSHL.

Immersion in an illusory world is possible by means of virtual reality (VR), where environmental perception is modified by artificial sensorial stimulation. The application of VR for the assessment and rehabilitation of pathologies affecting the vestibular system, in terms of both diagnosis and care, could represent an interesting new line of research. Our perception of reality is in fact based on static and dynamic spatial information perceived by our senses. During head movements in a virtual environment the images on the display and the labyrinthine information relative to the head angular accelerations differ and therefore a visuo-vestibular conflict is present. It is known that mismatches between visual and labyrinthine information may modify the vestibulo-oculomotor reflex (VOR) gain. We studied the post-immersion modifications in 20 healthy subjects (mean age 25 years) exposed to a virtual environment for 20 min by wearing a head-mounted display. VOR gain and phase were measured by means of harmonic sinusoidal stimulation in the dark before, at the end of and 30 min after VR exposure. A VOR gain reduction was observed in all subjects at the end of VR exposure which disappeared after 30 min. Our data show that exposure to a virtual environment can induce a temporary modification of the VOR gain. This finding can be employed to enable an artificial, instrumental modification of the VOR gain and therefore opens up new perspectives in the assessment and rehabilitation of vestibular diseases.

Sudden hearing loss can be found in systemic autoimmune diseases or it can be a symptom of an autoimmune disease of the inner ear. The present work has studied a group of patients with idiopathic sudden hearing loss to determine what role anti-endothelial cell antibodies (AECA) play as markers of immuno-mediated vasculitis of the inner ear. The study involved 32 patients with sudden deafness and 14 controls. The patients underwent otofunctional, neuroradiological, sero-microbiological and immunological testing. Using the indirect immunofluorescence technique, serum AECA were determined within 24 hours of hospitalization and three days after the onset of deafness. AECA positive patients (AECA+) were administered corticosteroid therapy (methylprednisone 1 mg/kg/die) for 1 month. A clinical follow-up was performed, including audiometry, 1 month after discharge and thereafter at three-month intervals (follow-up range: 8-18 months). AECA proved positive in 15/32 patients (47%) and in 2/14 of the controls (14%). The difference between the patients and the controls was statistically significant (p = 0.03). The 7 patient who showed no recovery after 1 month were all AECA+. None of the AECA+ patients showed other symptoms or a worsening of the hearing loss. In conclusion, the determination of non-specific autoantibodies vs. the inner ear, such as AECA, can be considered a useful clinical tool in differentiating between patients with idiopathic sudden hearing loss and those for which a diagnosis of immuno-mediated vasculitis of the inner ear is likely and for which prognosis is particularly unfavorable.

Sixteen patients affected by benign paroxysmal positional vertigo of the horizontal semicircular canal (BPPV-HSC) were investigated by means of dynamic posturography (DP) and during bithermal caloric stimulation. Data were compared to data from 40 patients with benign paroxysmal positional vertigo of the posterior semicircular canal (BPPV-PSC) and 20 healthy controls. No postural deficit was observed before or after a liberative Lempert's manoeuvre when patients were compared to control subjects. BPPV-PSC postural scores were significantly impaired compared to scores from the BPPV-HSC group. A residual significant postural impairment was also observed after a successful liberative manoeuvre in the BPPV-PSC group. Electronystagmographic recordings before recovery revealed significant hypoexcitability of the affected ear in 8/16 patients of the BPPV-HSC group. After the liberative manoeuvre, a symmetric bilateral response to caloric stimulation was recorded in all patients. Three main conclusions can be drawn from the present data. First, disorders of the horizontal semicircular canal do not change postural control. Second, dynamic posturography can detect the postural imbalance due to posterior semicircular canal dysfunction even after resolution of paroxysmal vertigo attacks. Third, utricular dysfunction can be ruled out as a cause of the residual postural deficit observed in BPPV-PSC patients. Therefore the recovery delay observed even 1 month after the liberative manoeuvre in the BPPV-PSC-group might be due to the persistence of small amounts of residual debris in the canal, to paralysis of ampullar receptors, or to the time needed for central vestibular re-adaptation.

Visually dependent postural stabilization decreases as a consequence of a long-standing reduction of visual cues in patients affected by congenital nystagmus. The aim of the present study was to verify whether the changes in postural control in this group of patients are due to ocular oscillations or to reduced visual acuity. Therefore, postural control was evaluated when the nystagmus was blocked by the blocking position or by prisms and compared with the postural score observed in a group of normal controls whose visual acuity had been artificially reduced to the same level as that of the patients using Bangerter's filters. The results show a statistically significant improvement of visually dependent postural stabilization when ocular oscillations are inhibited either by the gaze blocking position or by prisms. They also show that postural control in normal subjects with Bangerter's filters is reduced, but is still significantly better than that observed when ocular oscillations are inhibited in patients affected by congenital nystagmus. Our data strongly support the role of ocular oscillations in visually dependent postural control, since postural impairment recovered under any condition in which ocular oscillations were abolished, despite differences in visual acuity. Our data also show that reduced visual acuity decreases visually dependent postural control to a lesser degree than ocular oscillations. This could be due to the fact that ocular oscillations are a disturbing input, usually inhibited centrally, in order to avoid oscillopsia. This mechanism is probably responsible for the reduced role of visual cues in the postural control in this group of patients. The reduction of visual acuity, by comparison, merely causes a decrease in visual cues, depending on the degree of visual loss. It can be concluded that the impaired postural control in patients affected by congenital nystagmus is mainly due to ocular oscillations, with reduced visual acuity creating a

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The immune response is thought to play a role in dysregulating epithelial growth in cholesteatoma of the middle ear. Through immunohistochemistry (using 18 monoclonal antibodies) on 10 specimens from human middle ear cholesteatomas, T-helper cells mixed with plasma cells, macrophages and scattered T-suppressor and B cells, have been detected in the perimatrix. Mast cells have also been identified in the perimatrix, usually close to the epithelium. Elements positive for D-related human leukocyte antigens (HLA-DR) were more than half of the immune cells. The endothelium of the perimatrix showed a sharp reactivity to the intercellular adhesion molecule-1 (ICAM1) and to the endothelial derived leukocyte adhesion molecule-1 (ELAM1), which play a role in recluting inflammatory cells and modulating the immune response. The expression of ICAM1 in the basal layer of the matrix indicates the homing of inflammatory reactions at the epithelial-stromal junction of the cholesteatoma. An intense expression of interferon-gamma receptor (IFN gamma R) was found in the basal layers of the cholesteatoma matrix, and overexpression of the epithelial growth factor receptor (EGFR) was found in all layers of the matrix. These data support the hypothesis that the epithelial cells in middle ear cholesteatoma are in an activated state and that their hyperproliferation is mediated through cytokines and adhesion molecules.

Previous experiences on vestibular compensation showed that multisensorial stimulations affect postural unbalance recovery. Virtual Environment (VE) exposure seems very useful in vestibular rehabilitation, since the experience gained during VE exposure is transferable to the reai world. The rearrangement of the hierarchy of the postural cues was evaluated in 105 patients affected by visual, labyrinthic and somatosensory pathology in normal conditions and during sensoriai deprivation. They were divided into five groups according to pathology and compared to 50 normal controls. Our data show that VE exposure is a reliable method to identify the deficient subsystem and the level of substitution. Moreover, Virtual Reality (VR) would accelerate the compensation of an acute loss of labyrinthine function, related to adaptive modifications of thevestibulo-ocularandvestibulo-spinal reflexes, overstimulating the residual labyrinthine function. The residual labyrinthine function is poor in chronic bilateral vestibular deficit and VE exposure should provide sensory substitution or sensory motor reorganisation, thereby modulating the external spatial reference and promoting the reorganisation of the multiple sensory input. The potential for VE exposure perspectives seerns very promising when dealing with the vestibular system where there is a continuous rearrangement of different sensorial informations as a result of environmental and age-related changes.

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Immunoscintigraphy with 111In-F(ab')2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n = 14), recurrences (n = 3) and suspected posttherapy lymph node metastases (n = 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100% and a sensitivity of 90%. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer. © 1997 Chapman and Hall ltd.

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.

Although human papillomaviruses (HPVs) have been found in many, but not all, tumours of the oral cavity, nose, pharynx and larynx, the true role of HPV in malignant tumours of the head and neck is still unclear. The presence of HPV DNA was investigated in 45 fresh squamous cell carcinoma (SCC) specimens and in 29 normal mucosa specimens collected from 45 primary laryngeal SCC patients. HPV DNA was detected using the polymerase chain reaction (PCR) with consensus primers that detect HPV types 6, 11, 16 and 18.9 of the 45 patients (20%) were HPV positive; the presence of HPV was also detected in the corresponding normal laryngeal mucosa of four of the 29 specimens (14%). No statistically significant differences were found between the presence of HPV DNA in normal specimens and in neoplastic mucosa specimens. No correlation was found between HPV DNA positive tumours and size, T classification, lymph node involvement and histological grading. This study adds further evidence suggesting a possible role of HPV DNA infection in laryngeal carcinogenesis.

Granulocytic sarcoma (chloroma) is a rare solid, extramedullary tumour composed of immature granulocytes, occurring during granulocytic leukemia. Leukemic involvement of the temporal bone is not uncommon and may present in a variety of ways. Symptomatic facial nerve paralysis is one of these. The authors report a case of facial nerve paralysis as the presenting symptom of leukemic relapse in a 16-year-old white male, affected by acute myelogenous leukemia FAB M2, karyotype 46xy, T8;21.

The clinical findings, histopathology, management and outcome of 31 patients with verrucous squamous cell carcinoma of the larynx (VSCC) are discussed. Laryngeal VSCC is a rare, highly differentiated variant of SCC and has specific morphological features and clinical behavior. A close liaison between the laryngologist and pathologist is needed to formulate a correct diagnosis, because this tumor appears to be malignant clinically and histologically benign. A low-power magnification of multiple large specimens, including the deep margins of the lesion, is required in order to differentiate VSCC from keratosis, verruca vulgaris or SCC with verrucous appearance, and to detect underlying microscopic foci of invasive SCC within or adjacent to a verrucous carcinoma. Long-lasting hoarseness was the most common symptom as the glottic region was the most common site of VSCC. Presumed clinically positive N1 lymph nodes were observed in the necks of 7 patients, but none had metastatic disease on histopathological study. Surgery alone was the most effective form of treatment, as it allowed a good outcome of all treated patients. Surgery plus radiotherapy was associated with an early recurrence and a poor outcome in 2 of 7 patients treated. The generally 'benign' behavior of VSCC allows for conservative surgery, with complete endoscopic resection using the carbon dioxide laser representing a more conservative surgical approach. Neck dissection is not indicated due to the non-metastatic behavior of this tumor.

The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV-DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR-subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa s

In the cat, inspiratory opening of the paralyzed glottis recovered after unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by phrenic axons. The morphometric analysis of the regenerated recurrent laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after the nerve anastomosis, more than 500 myelinated axonal branches repopulated the RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in normal phrenic and RLN (8 to 10 microns), and the mean internode length was about half that of the normal RLN. Histochemical examination of the PCA muscle revealed that muscle fiber composition (44% type I and 56% type II muscle fiber) was fairly similar to that of normal PCA. The contraction time of the reinnervated muscles was as long as 60 msec at the time of movement recovery, but it shortened to 25 to 30 msec when the reinnervation time increased. These anatomical and functional results support the choice of the phrenic nerve for laryngeal reinnervation

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The aim of this study was to provide the bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by the superior root of the right phrenic nerve. In six adult cats, the right phrenic root was anastomosed to the distal stump of the transected recurrent laryngeal nerve (RLN) on the same side. The RLN adductor branch was then cut and anastomosed to a nerve graft whose end was carried contralaterally and sutured to the left RLN or to the left PCA muscle. The phrenic fibers regrowing along the RLN abductor branch reinnervated the right PCA muscle and restored the inspiratory abduction of the right vocal cord in all the animals. In five of the six cats, the fibers regenerated through the RLN adductor branch and the graft reached the left PCA muscle and also restored the inspiratory opening of the larynx on the left side. Histological nerve examination revealed a fairly symmetrical distribution of the regenerated phrenic axons to the right and left PCA muscles

Comprend : Le Jugement de Salomon / avec M. GIGNAC, G. VIVANTE, sopr. N. ADAMI, ténor - G. FERREIN, basse - Histoire de Job / avec F. OTTAVIANI, sop. - G. SALVI, alto - G. FERREIN, basse - Le Festin de Balthazar / avec M. GIGNAC, sopr. - G. SALVI, alto E. PAPAZIAN et N. ADAMI, ténor - G. FERREIN, basse, BnF-Partenariats, Collection sonore - Believe, Contient une table des matières