[Show abstract][Hide abstract] ABSTRACT: Purpose - Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC).
Methods - Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1-T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis.
Results - Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (p=0.031). Most tumors had variable degrees (mean expression 80.7%±23.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS.
Conclusions - In spite of these results, it is worth further investigating the role of pSTAT3 (serine and tyrosine-phosphorylated STAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition.
[Show abstract][Hide abstract] ABSTRACT: Objectives. Angiogenin (ANG) and Maspin are important pro- and anti-angiogenic regulators, respectively, in numerous malignancies. The aim of this investigation was to study the potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC).
Methods. Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone. The subcellular pattern of Maspin expression was considered. Univariate and multivariate statistical models were applied for prognostic purposes.
Results. On univariate analysis, a different ANG expression level was found in patients stratified by subcellular Maspin expression pattern: mean ANG expression was higher in patients with a non-nuclear MASPIN expression than those with a nuclear pattern (p=0.002). Disease-free survival (DFS) (in months) differed significantly when patients were stratified by N stage (p=0.01). Patients with a non-nuclear Maspin expression pattern (only cytoplasmic or no reactivity) had a significantly higher recurrence rate (p=0.0009), and shorter DFS (p=0.01) than those with a nuclear Maspin pattern. Mean ANG expression was significantly higher in cases with loco-regional recurrent disease (p=0.007); and patients with an ANG expression >5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (p=0.007). On multivariate analysis, ANG expression >5.0% was a significant, independent, negative prognostic factor in terms of DFS (p=0.041).
Conclusion. Our results support the hypothesis that a higher ANG expression is associated with a non-nuclear pattern of Maspin expression in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.
[Show abstract][Hide abstract] ABSTRACT: Objectives. Before the widespread use of antibiotics, most deep neck infections (DNIs) stemmed from complicated pharyngeal infections. Nowadays, they seem to be due mainly to dental infections. In 2010, our group reported that DNIs originated from a major salivary gland in 14% of cases. The main endpoint of the present investigation was to review our experience of the diagnosis and treatment of DNIs of salivary gland origin. We also compared the characteristics of DNIs originating from salivary glands with those originating elsewhere.
Methods. Between 2000 and 2011, 44 patients were treated for DNIs of salivary origin at our institution. These patients were compared with 191 cases of DNI diagnosed as having other sites of origin.
Results/Conclusions. In the present series, DNIs originating from a major salivary gland accounted for 19% of all cases of DNI of known origin. Patients with DNI of salivary gland origin were more likely to be elderly than those whose DNI originated from elsewhere (p=0.000). Our multivariate statistical model showed that comorbidities (p=0.051, statistical trend) and the need for surgical treatment (p=0.028) independently predicted long-term hospitalization for DNIs originating from a major salivary gland.
Key words: major salivary glands; deep neck infections; diagnosis; treatment; prognosis
American Journal of Otolaryngology 07/2015; 36:559-564. DOI:10.1016/j.amjoto.2015.01.003 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) prognosis is definitely related to lymph node metastasis. Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the plasticity and motility required for tumor progression and metastasis. The aim of this study was to investigate the role of EMT in the prognosis of LSCC.
Immunohistochemical analysis of E-cadherin, N-cadherin, Snail, Slug, ZEB1, and ZEB2 was performed in 37 consecutive LSCC cases. Low E-cadherin and high Slug levels correlated with both disease recurrence (p = 0.02 and p = 0.01) and shorter DFS (p = 0.04 and p = 0.02). Relative expression of CDH1, SNAI2, miR-1, and miR-200 family were also evaluated. CDH1, miR-200a, and miR-200c down-regulation and SNAI2 over-expression were significantly associated with disease recurrence (p = 0.03, p = 0.02, p = 0.04, and p = 0.04, respectively).
EMT increases tumor recurrence risk and shortens DFS in LSCC. E-cadherin and Slug immunohistochemical analysis could be useful to identify patients requiring a more aggressive treatment after surgery. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: With the growing acceptance of nonsurgical therapies for laryngeal squamous cell carcinomas (LSCC), it has become important to delineate surgical salvage strategies for disease recurrences. Total laryngectomy (TL) is often recommended but appropriately selected laryngeal recurrences may be treated successfully with partial laryngectomy. Using proper selection criteria for conservative salvage laryngeal surgery, laryngeal function can be preserved with oncological efficacy.
The most appealing feature of salvage transoral laser surgery (TLS) is the opportunity to make tumor-tailored excisions without any reconstructive limitations and retaining the option to switch to open partial laryngectomy. A recent detailed review of 11 series found a pooled local control rate of 57% after a first TLS procedure, and 64% after repeated TLS procedures. Supracricoid laryngectomy (SCL) seems to achieve good local control rates in selected cases of recurrent supraglottic-glottic carcinoma: one review considering 7 series calculated that 85% of the patients treated with salvage SCL after radiotherapy experienced no local recurrence; and TL after salvage SCL afforded an overall local control rate of approximately 65%.
Neck dissection is mandatory in all cases of local LSCC recurrence with evidence of neck metastases, and routine elective neck dissection is recommended for recurrent supraglottic and transglottic cancers.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate if any of the three awake procedures [fiberoptic nasopharyngoscopy with modified Müller Maneuver (FNMM), nasal snoring endoscopy (NSE), or oral snoring endoscopy (OSE)] could efficiently predict the grade or pattern of upper airway (UA) collapse found with drug-induced sleep endoscopy (DISE), which is considered by many authors as the current gold standard in optimizing obstructive sleep apnea syndrome (OSAS) patient selection for UA surgery. Twenty consecutive patients (simple snorers and OSAS patients) were studied with FNMM, NSE, OSE, and DISE. The inter-test agreement was evaluated with Cohen’s kappa coefficient (κ). In the current series, we found that NSE and OSE were better than FNMM in predicting the pattern of collapse found with DISE. A significant pattern agreement between NSE and DISE was present in all sub-sites, and the agreement was measured with a scale proposed by Landis and Koch as: moderate in velo- and oropharynx (κ = 0.52, p = 0.001, and κ = 0.47, p = 0.003, respectively), and substantial in hypopharynx (κ = 0.63, p κ = 0.82, p κ = 0.55, p = 0.0002); while a trend towards significance was found at velopharyngeal level (κ = 0.20, p = 0.07). FNMM showed a fair pattern agreement with DISE only at oropharyngeal level (κ = 0.31, p = 0.009); while in the other sub-sites, no significant agreement was found. NSE and OSE are new promising diagnostic tools in OSAS patients. Further investigations are needed to see if they could predict the effectiveness of UA surgery.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 01/2015; 272(7). DOI:10.1007/s00405-014-3473-9 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite appropriate surgical therapy, 5–10 % of patients with chronic rhinosinusitis (CRS) and nasal polyps (NP) experience disease recurrences. It has been suggested that angiogenesis may relate to the pathogenesis and prognosis of CRS with NP. Endoglin (CD105) is a component of the receptor complex of transforming growth factor-beta, a pleiotropic cytokine that modulates angiogenesis. A series of patients treated surgically for CRS with NP was analyzed to assess the relationship between CD105 expression, main clinicopathological features, and recurrence rate. The immunohistochemical expression of CD105
was assessed in 70 patients consecutively operated for CRS with NP. In the univariate setting, the presence of CD105 (1/0) showed a trend towards a significant association with increasing NP dimensions (p = 0.054). Intensity of CD105 reaction was also significantly associated with NP size (0.04) and with an eosinophilic histology (p = 0.048). In our multivariate setting, only asthma (p = 0.016), hypereosinophilia (p = 0.022), and preoperative polyposis score (p = 0.046) retained their independent prognostic significance in relation to NP recurrence. Further efforts are needed to elucidate the biological, angiogenic and proliferative mechanisms behind recurrent NP. Our preliminary results support the clinical utility of extra postoperative care, in terms of closer follow-ups and medication with oral anti-histamines, topical and/or oral steroids, and antileukotrienes in patients with asthma, advanced nasal polyposis at presentation, and serum hypereosinophilia.
Keywords Nasal polyposis, Surgery, Nasal polyps relapse, CD105
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 01/2015; DOI:10.1007/s00405-014-3456-x · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Adenosquamous carcinoma (ASC) of the head and neck is a rare malignancy characterized by loco-regional and distant aggressiveness. At histology, ASC reveals two distinct, juxtaposed components, squamous cell carcinoma (SCC), and true adenocarcinoma.
The immunohistochemical expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of laryngeal ASC.
The patient had no regional lymph node metastases, but developed a recurrence in neck soft tissues shortly after primary radical surgery. The laryngeal surgical specimen had the typical morphological features of ASC. The tumor's squamous and glandular components were both strongly and diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in the specimens. The patient underwent salvage extended radical neck dissection and received postoperative radio-chemotherapy. At 4-month follow-up control, neck recurrence was found. Palliative chemotherapy was instituted.
An accurate histological and immunohistochemical diagnosis is mandatory to differentiate ASC from conventional SCC. Radical surgical excision is recommended for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases, but there are no widely accepted indications for these treatments.
American Journal of Otolaryngology 12/2014; 36(3). DOI:10.1016/j.amjoto.2014.12.007 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early oral contraceptive pills (OCP) had higher estrogen levels and have been thought to cause nasal obstruction in about 40% of women users. A recent small study conducted on women taking OCP showed no significant effects on nasal patency. The aim of the present study was to analyse in a large number of volunteers if Peak Nasal Inspiratory Flow (PNIF) values could be influenced by modern OCP.
PNIF was measured in 257 women (from 14 to 51 years old), divided into two groups: the study group composed of 109 healthy women taking modern OCP; the control group composed of 148 healthy women who did not take OCP. 9 women in the study group were excluded because of allergic disease, 248 females were finally considered. Data were statistically analysed and figures/tables were produced to see the effect of OCP on PNIF.
The present study could not show any effect of OCP on nasal function. Moreover, while height influenced PNIF in both groups, age was not statistically significant.
From the present study, it seems that OCP could have no effects on nasal airflow, confirming that modern OCP with lower estrogen doses should not affect nasal mucosa or nasal patency.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23-H1) with conventional criteria could better discriminate higher-risk patients warranting postoperative RT.
The study involved 76 consecutively operated patients with laryngeal SCC not recommended for postoperative RT, in accord with current guidelines.
On multivariate statistical modeling, non-nuclear MASPIN expression (p = .022), a CD105 expression ≥ 5.28% in vascular endothelial cells (p = .003), an nm23-H1 nuclear expression in carcinoma cells ≤ 12.0% (p = .028), and an ANG expression ≥ 5.0% (p = .07, statistical trend) showed a negative prognostic significance. The discriminatory power for disease recurrence of the 4 considered biomarkers generated an area under the curve (AUC; receiver operating characteristic [ROC]) of 0.872. The Hosmer-Lemeshow scale indicated an excellent discriminatory power.
This panel's ability to predict laryngeal SCC recurrence warrants further prospective, randomized studies to assess its use among the parameters routinely considered before recommending postoperative RT for patients with laryngeal SCC.
Head & Neck 11/2014; 36:1534-1540. DOI:10.1002/hed.23493 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Postoperative radiotherapy (PORT) improves locoregional control and survival rates for patients with advanced laryngeal carcinoma (LSCC), but reported outcomes after PORT for LSCC vary considerably. Predictive markers (including biomarkers) are needed for LSCC to orient the choice of the most appropriate adjuvant therapy for individual patients. The aim of this study was to identify a panel of LSCC tissue markers (considering EGFR, mTOR, survivin, Bcl-2, angiogenin, endoglin [CD105], nm23-H1) capable of pinpointing patients at higher risk of recurrence among 33 LSCC cases treated with PORT.
Univariate analysis found 4 biomarkers (mTOR, nuclear survivin, CD105, non-nuclear nm23-H1) significantly associated with LSCC recurrence. A collinearity emerged between mTOR and CD105 expressions. The predictive role of two different panels (panel 1: mTOR, nuclear survivin, non-nuclear nm23-H1; panel 2: CD105, nuclear survivin, non-nuclear nm23-H1) was considered. According to the Hosmer and Lemeshow scale, panel 1 demonstrated an outstanding discriminatory power (AUC 0.903) in predicting LSCC recurrence after PORT. Panel 2 had an excellent discriminatory power too (AUC 0.899).
Both panels of biomarkers showed an important discriminatory power in pinpointing patients at higher risk of recurrence after PORT for LSCC who could reasonably benefit from adjuvant postoperative chemo-RT.
American Journal of Otolaryngology 11/2014; 35:771-778. DOI:10.1016/j.amjoto.2014.06.005 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) recurrences are very difficult to manage in elderly patients (age ≥65 years), because treatment carries significant morbidity and mortality. The aim of this study was to develop a panel of parameters (clinicopathological variables or biomarkers) to improve our ability to detect elderly patients at higher risk of LSCC recurrence. Maspin, nm23-H1, and CD105 were investigated using immunohistochemistry on surgical specimens from 46 elderly patients treated for LSCC. After univariate analysis identified parameters associated with LSCC recurrence, a multivariate prognostic model was constructed. At univariate analysis, a higher recurrence rate was significantly associated with nm23-H1 nuclear expression in carcinoma cells ≤2.0 % (p = 0.01), CD105 expression in intratumoral vascular endothelial cells ≥5.28 % (p = 0.04), and pN+ status (p = 0.04). Multivariate modeling confirmed that nuclear nm23-H1 ≤2.0 % (p = 0.009) and CD105 ≥5.28 % (p = 0.013) had a negative prognostic significance in terms of disease recurrence, while pN+ status showed a trend toward significance (p = 0.05). We thus obtained a panel comprising two biomarkers and neck lymph node status that revealed an excellent discriminatory power [AUC (ROC) of 0.81] in terms of the risk of LSCC recurrence. The panel achieved a specificity of 96 % and a positive predictive value of 93 %. We identified a panel with an excellent discriminatory power in identifying elderly patients at higher risk of recurrence after treatment for LSCC. These patients would benefit from a more aggressive primary treatment.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 10/2014; DOI:10.1007/s00405-014-3310-1 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To discover the anatomist who first identified the upper oesophageal sphincter.
The authors searched dozens of antique anatomy textbooks kept in the old section of the 'Vincenzo Pinali' Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter.
The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as 'An Anatomical History on the Organs of Voice and Hearing …'), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… ('Treatise on the Human Ear …').
Anatomists Casserius and Valsalva can be considered the discoverers of the 'oesophageal sphincter'.
The Journal of Laryngology & Otology 10/2014; 128(10):1-5. DOI:10.1017/S0022215114002035 · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To assess the effectiveness of mandibular advancement devices (MADs) for the treatment of obstructive sleep apnea syndrome (OSAS) over a long-term follow-up in patients non-compliant with continuous positive airway pressure (CPAP) and to identify potential predictive factors of response to MADs.
Fifteen OSAS patients were enrolled. Apnea-hypopnea index (AHI) and daytime sleepiness were assessed at baseline and at the end of follow-up. Potential baseline predictors of treatment effectiveness were assessed.
AHI and Epworth Sleepiness Scale (ESS) scores improved significantly with MADs. Sixty per cent of patients were 'responders', of whom 33% were 'full responders'. Sixty-seven per cent of patients showed total compliance. No correlations between the potential predictors and the response to MAD therapy were found.
Effectiveness of MAD therapy was shown over a long-term follow-up in OSAS patients with low compliance to CPAP. Efforts to identify predictive success factors fell short.
Cranio: the journal of craniomandibular practice 10/2014; 32(4):254-259. DOI:10.1179/2151090314Y.0000000003 · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hearing, Balance and Communication (formerly Audiological Medicine) 2014;12:182-8.
Objective: With an estimated incidence of 77 new cases per 100,000 population aged 65 years or above, idiopathic sudden sensorineural hearing loss (ISSNHL) is a common clinical finding in elderly patients. There is a shortage of information on the clinical factors capable of predicting hearing recovery and response to therapy. The aim of the present study was to retrospectively investigate the prognostic value of clinical variables in relation to hearing recovery in a cohort of consecutive elderly patients with ISSNHL. Study design: This investigation considered 49 consecutive elderly patients (≥ 65 years of age) treated for ISSNHL. Clinical parameters (signs, symptoms, comorbidities and treatments) and audiometric data were analysed using univariate and multivariate statistical approaches for prognostic purposes, i.e. to identify any correlation with hearing recovery, expressed according to Wilson's criteria. Results/Conclusions: No clinical signs and symptoms, and no specific therapeutic approaches correlated significantly with hearing recovery after ISSNHL in our multivariate model (p > 0.05). In the univariate analysis, vascular disease correlated significantly with hearing gain after treatment (p = 0.01). Further studies based on larger cohorts (especially in a prospective setting) are needed to further elucidate the prognostic role of clinical parameters in ISSNHL involving elderly patients.
Audiological Medicine 09/2014; 12:182-188. DOI:10.3109/21695717.2014.965498