Human papillomavirus (HPV) oncogenic activity is the result of viral oncogene E6 and E7 expressio... more Human papillomavirus (HPV) oncogenic activity is the result of viral oncogene E6 and E7 expression in infected cells. Oncogene expression analysis is, however, not part of the routine diagnostic evaluation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) since it requires fresh tumor tissue. We compared the diagnostic accuracy of several methods commonly employed for HPV characterization in OPSCC with the results of the newly available HPV E6/E7 mRNA in situ hybridization (ISH) on formalin-fixed, paraffin-embedded biopsy samples, in order to establish if the latter should be introduced in the diagnostic routine to increase accuracy when fresh tissue is not available. p16 immunostain, DNA ISH for high-risk HPV genotypes, SPF LiPA amplification and genotyping, and HPV16 E6 amplification were performed on 41 consecutive OPSCC samples. Twenty (48.7%) cases were positive by mRNA ISH; sensitivity and specificity were 100% and 90% for p16, 90% and 100% for DNA ISH, 70% and 76% for SPF10 LiPA, 90% and 76% for E6 amplification. A diagnostic algorithm considering p16 immunostain as first step followed by either high-risk HPV DNA ISH or HPV16 E6 amplification in p16-positive cases correctly characterized 90% of mRNA-positive and all mRNA-negative cases; combining the 3 tests correctly identified all cases. While no stand-alone test was sufficiently accurate for classifying HPV-associated OPSCC, the high sensitivity and specificity of the established combination of p16 immunostain, DNA ISH, and HPV16 DNA amplification suggests that the introduction of labour- and cost-intensive mRNA ISH, is not necessary in the diagnostic routine of oropharyngeal tumors.
The head impulse test (HIT) is nowadays recognized as the gold standard for clinical testing of t... more The head impulse test (HIT) is nowadays recognized as the gold standard for clinical testing of the angular vestibulo-ocular reflex (VOR). By imposing unpredictable, abrupt head rotations in canal pairs' planes it aims at unveiling the dysfunction of the semicircular canal towards which the head is rotated based on Ewald's II law. Functional testing of the VOR aims at assessing the ability of the reflex to stabilize gaze in space and thus allow clear vision during head movements. The HIT device (HITD) approach exploits impulsive head rotations spawning a range of angular accelerations while requiring subjects to identify optotypes briefly displayed on a screen. Here we also recorded eye movements, so that the evaluation of the individual subject is based both on the VOR gain and on the percentage of correct answers with respect to a population of controls. Here we used the HITD to study 14 patients suffering from vestibular neuritis and 7 of those were re-tested after three months. We found that the HITD was able to unveil the ipsilesional deficit and the contralesional impairment, together with the improvement in the follow-up test.
The gastric pull-up or pharyngogastroplasty is the most widely used technique in reconstructing t... more The gastric pull-up or pharyngogastroplasty is the most widely used technique in reconstructing the digestive tract in cases of distal oesophageal tumours. This operation consists of drawing the stomach or part of it up through the chest and mediastinic region to the neck where a mucosal anastomosis with the residual pharyngeal tract is made. The most feared complication is proximal necrosis of the gastric stump with salivary fistulae usually followed by a mediastinitis. In the presence of such a complication the surgeon must tackle the challenge of reconstructing the missing part of the intrathoracic digestive tract. We describe the case of a patient in whom the missing intrathoracic oesophagus, following complete necrosis of a previously performed pharyngogastroplasty, was reconstructed using a revascularized lateral thigh free flap.
Haemangiopericytomas are vascular tumours derived from Zimmerman's pericytes; they account for ab... more Haemangiopericytomas are vascular tumours derived from Zimmerman's pericytes; they account for about 1% of all vascular tumours. About 5% of the cases occur in the nasal cavity and usually show well-differentiated tumours with low potential for local recurrence or metastasis. The treatment of choice is surgical resection. We present a case of nasal haemangiopericytoma treated by endoscopic resection, and we emphasise the advantages of this minimally invasive method compared with traditional methods.
In recent years, several titration or on-demand protocols using low-dose repeated intratympanic (... more In recent years, several titration or on-demand protocols using low-dose repeated intratympanic (IT) gentamicin injections have been adopted for the vertigo control in unilateral medical refractory Menière's disease (MD). Because of the frequent recurrence and the need to treat the patients several times, it is difficult to strictly follow the 1995 AAO-HNS criteria to classify the results. The Kaplan-Meier analysis provides an effective and simpler method to address these concerns. We report the results of a long-term study (7 years) on a large population of MD patients (174) treated with on-request low-dose delayed IT gentamicin injections analysed using the Kaplan-Meier survival method. Effective vertigo control was obtained with a single injection in 40.2% of the patients (excellent responders) and with repeated injections (2-9) in 43.7% of the patients (moderate responders). Only six patients (3.5%) needed to be submitted to vestibular neurectomy because of the persistence of vertigo attacks (non-responders). A subgroup of 22 patients (12.6%) reporting a late recurrence of vertigo attacks after an initial vertigo-free interval lasting more than 2 years (short-term responders) were successfully treated with a further cycle of injections. In no cases, we observed significant signs of cochlear or vestibular toxicity. Kaplan-Meier survival analysis provided an excellent method for reporting treatment success or failure in patients followed for variable length of time with our kind of protocol.
Primary atrophic rhinitis is a chronic inflammation of the nasal mucosa characterized by atrophy ... more Primary atrophic rhinitis is a chronic inflammation of the nasal mucosa characterized by atrophy of the mucous and bony tissue of the turbinates and by a thick, dense secretion, which quickly forms a characteristically fetid-smelling, greenish crust. We report the results of the clinical, genetic and immunologic investigations performed on eight subjects (three with ozena and five asymptomatic), members of the same familial group. The presence of the disease in the family fits well with dominant inheritance. All the culture specimens from the patients affected by ozena were positive for Klebsiella ozaenae, and one of them was also positive for Pseudomonas aeruginosa. All the three patients with ozena and two of the five apparently unaffected family members were positive for antinuclear antibodies. Immunoblotting showed a reactivity to a 50-kD protein, which was not identified by the common, recognized nuclear autoantigens. This was present in one of the three patients and three of the five other family members. Positivity for IgG-class anticardiolipins was correlated with disease manifestation in that it was found in two of the three patients and only in one of the five asymptomatic family members. The hypothesis of a genetic factor that could drive the chronicity of the inflammatory pattern of a pre-existing infectious nasal disease is suggested.
Human papillomavirus (HPV) oncogenic activity is the result of viral oncogene E6 and E7 expressio... more Human papillomavirus (HPV) oncogenic activity is the result of viral oncogene E6 and E7 expression in infected cells. Oncogene expression analysis is, however, not part of the routine diagnostic evaluation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) since it requires fresh tumor tissue. We compared the diagnostic accuracy of several methods commonly employed for HPV characterization in OPSCC with the results of the newly available HPV E6/E7 mRNA in situ hybridization (ISH) on formalin-fixed, paraffin-embedded biopsy samples, in order to establish if the latter should be introduced in the diagnostic routine to increase accuracy when fresh tissue is not available. p16 immunostain, DNA ISH for high-risk HPV genotypes, SPF LiPA amplification and genotyping, and HPV16 E6 amplification were performed on 41 consecutive OPSCC samples. Twenty (48.7%) cases were positive by mRNA ISH; sensitivity and specificity were 100% and 90% for p16, 90% and 100% for DNA ISH, 70% and 76% for SPF10 LiPA, 90% and 76% for E6 amplification. A diagnostic algorithm considering p16 immunostain as first step followed by either high-risk HPV DNA ISH or HPV16 E6 amplification in p16-positive cases correctly characterized 90% of mRNA-positive and all mRNA-negative cases; combining the 3 tests correctly identified all cases. While no stand-alone test was sufficiently accurate for classifying HPV-associated OPSCC, the high sensitivity and specificity of the established combination of p16 immunostain, DNA ISH, and HPV16 DNA amplification suggests that the introduction of labour- and cost-intensive mRNA ISH, is not necessary in the diagnostic routine of oropharyngeal tumors.
The head impulse test (HIT) is nowadays recognized as the gold standard for clinical testing of t... more The head impulse test (HIT) is nowadays recognized as the gold standard for clinical testing of the angular vestibulo-ocular reflex (VOR). By imposing unpredictable, abrupt head rotations in canal pairs' planes it aims at unveiling the dysfunction of the semicircular canal towards which the head is rotated based on Ewald's II law. Functional testing of the VOR aims at assessing the ability of the reflex to stabilize gaze in space and thus allow clear vision during head movements. The HIT device (HITD) approach exploits impulsive head rotations spawning a range of angular accelerations while requiring subjects to identify optotypes briefly displayed on a screen. Here we also recorded eye movements, so that the evaluation of the individual subject is based both on the VOR gain and on the percentage of correct answers with respect to a population of controls. Here we used the HITD to study 14 patients suffering from vestibular neuritis and 7 of those were re-tested after three months. We found that the HITD was able to unveil the ipsilesional deficit and the contralesional impairment, together with the improvement in the follow-up test.
The gastric pull-up or pharyngogastroplasty is the most widely used technique in reconstructing t... more The gastric pull-up or pharyngogastroplasty is the most widely used technique in reconstructing the digestive tract in cases of distal oesophageal tumours. This operation consists of drawing the stomach or part of it up through the chest and mediastinic region to the neck where a mucosal anastomosis with the residual pharyngeal tract is made. The most feared complication is proximal necrosis of the gastric stump with salivary fistulae usually followed by a mediastinitis. In the presence of such a complication the surgeon must tackle the challenge of reconstructing the missing part of the intrathoracic digestive tract. We describe the case of a patient in whom the missing intrathoracic oesophagus, following complete necrosis of a previously performed pharyngogastroplasty, was reconstructed using a revascularized lateral thigh free flap.
Haemangiopericytomas are vascular tumours derived from Zimmerman's pericytes; they account for ab... more Haemangiopericytomas are vascular tumours derived from Zimmerman's pericytes; they account for about 1% of all vascular tumours. About 5% of the cases occur in the nasal cavity and usually show well-differentiated tumours with low potential for local recurrence or metastasis. The treatment of choice is surgical resection. We present a case of nasal haemangiopericytoma treated by endoscopic resection, and we emphasise the advantages of this minimally invasive method compared with traditional methods.
In recent years, several titration or on-demand protocols using low-dose repeated intratympanic (... more In recent years, several titration or on-demand protocols using low-dose repeated intratympanic (IT) gentamicin injections have been adopted for the vertigo control in unilateral medical refractory Menière's disease (MD). Because of the frequent recurrence and the need to treat the patients several times, it is difficult to strictly follow the 1995 AAO-HNS criteria to classify the results. The Kaplan-Meier analysis provides an effective and simpler method to address these concerns. We report the results of a long-term study (7 years) on a large population of MD patients (174) treated with on-request low-dose delayed IT gentamicin injections analysed using the Kaplan-Meier survival method. Effective vertigo control was obtained with a single injection in 40.2% of the patients (excellent responders) and with repeated injections (2-9) in 43.7% of the patients (moderate responders). Only six patients (3.5%) needed to be submitted to vestibular neurectomy because of the persistence of vertigo attacks (non-responders). A subgroup of 22 patients (12.6%) reporting a late recurrence of vertigo attacks after an initial vertigo-free interval lasting more than 2 years (short-term responders) were successfully treated with a further cycle of injections. In no cases, we observed significant signs of cochlear or vestibular toxicity. Kaplan-Meier survival analysis provided an excellent method for reporting treatment success or failure in patients followed for variable length of time with our kind of protocol.
Primary atrophic rhinitis is a chronic inflammation of the nasal mucosa characterized by atrophy ... more Primary atrophic rhinitis is a chronic inflammation of the nasal mucosa characterized by atrophy of the mucous and bony tissue of the turbinates and by a thick, dense secretion, which quickly forms a characteristically fetid-smelling, greenish crust. We report the results of the clinical, genetic and immunologic investigations performed on eight subjects (three with ozena and five asymptomatic), members of the same familial group. The presence of the disease in the family fits well with dominant inheritance. All the culture specimens from the patients affected by ozena were positive for Klebsiella ozaenae, and one of them was also positive for Pseudomonas aeruginosa. All the three patients with ozena and two of the five apparently unaffected family members were positive for antinuclear antibodies. Immunoblotting showed a reactivity to a 50-kD protein, which was not identified by the common, recognized nuclear autoantigens. This was present in one of the three patients and three of the five other family members. Positivity for IgG-class anticardiolipins was correlated with disease manifestation in that it was found in two of the three patients and only in one of the five asymptomatic family members. The hypothesis of a genetic factor that could drive the chronicity of the inflammatory pattern of a pre-existing infectious nasal disease is suggested.
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Papers by Marco Benazzo