A Pathophysiological Approach to Spontaneous Orbital Meningoceles: Case Report and Systematic Review.

BACKGROUND: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. METHODS: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. RESULTS: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. CONCLUSIONS: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount.

Prognostic Value of Anteroposterior Extension in Oral Tongue and Floor Squamous Cell Carcinoma.

Importance: The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor. Objective: To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC). Design, Setting, and Participants: This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging. Exposures: Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines. Main Outcomes and Measures: Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs. Results: Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs. Conclusions and Relevance: In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.

The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes.

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.

Structured histopathology and laboratory evidence in nasal polyposis with different pathogenesis.

PURPOSE: Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD), intrinsic asthma, eosinophilic granulomatosis with polyangiitis (EGPA) and odontogenic sinusitis may be associated with nasal polyps. The aim of the study was to compare circulating inflammatory cells and structural histopathology of these groups of nasal polyposis. METHODS: We retrospectively evaluated 71 patients with nasal polyps stratified according to the above-mentioned pathogenesis. All patients underwent preoperative laboratory investigations and primary endoscopic sinus surgery. Surgical specimens were submitted to structured histopathological evaluation. RESULTS: The median tissue eosinophil count (cells/HPF) was significantly different between the considered groups of nasal polyposis (p=0.0004). The median of NERD sub-cohort was significantly higher than intrinsic asthma (p=0.0030), odontogenic CRS (p=0.0001) and EGPA ones (p=0.0094). Eosinophilic aggregates positive rate was significantly higher in NERD sub-cohort than in odontogenic CRS (p=0.0072), EGPA (p=0.0497) and asthma (p=0.0188) ones. EGPA sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0105) and intrinsic asthma ones (p=0.0040). Odontogenic CRS sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0140) and asthma ones (p=0.0096). EGPA sub-cohort had a higher presence of fibrosis than NERD (p=0.0237) and odontogenic CRS sub-cohort (p=0.0107). Odontogenic sub-cohort had a lower sub-epithelial edema positive rate than NERD (p=0.0028) and asthma (p=0.0149) ones. CONCLUSIONS: Structural histopathology may identify nasal polyps histotypes with different morphological patterns. The identified histopathological features can facilitate the recognition of rational therapeutic and follow-up approaches that consider the tissue modifications associated with the response to drugs and surgery.

Odontogenic Chronic Rhinosinusitis: Structured Histopathology Evidence in Different Patho-Physiological Mechanisms.

An increased odontogenic chronic rhinosinusitis (oCRS) occurrence rate has quite recently been reported, likely due to an intensification of conservative dental surgery and implantology. The main aim of the study was to report for the first time the structured histopathological characteristics of the surgical specimens of oCRS. Possible associations between histopathological features and oCRS patho-physiological mechanisms were also evaluated. Structured histopathology features were investigated in the sinonasal mucosa tissue of 42 consecutive oCRS patients.Mean tissue eosinophil counts were significantly different between oCRS with radicular cysts, dental implants, or other dental diseases (p =0.0118): mean tissue eosinophil count was higher in oCRS with dental implants. Sub-epithelial edema score and squamous metaplasia presence were significantly different when comparing the above-mentioned sub-cohorts of oCRS (p =0.0099 and p =0.0258). In particular, squamous metaplasia was more present in oCRS cases with radicular cysts than in those with a dental implant (p =0.0423). Fibrosis presence was significantly different comparing the three sub-cohorts of oCRS (p =0.0408), too. This preliminary evidence supports the hypothesis that: (i) structural histopathology can become a useful tool for clinic-pathological practice in diagnostic, therapeutic, and prognostic terms in CRS; (ii) that oCRS, as CRS in general, is a histo-pathologically heterogeneous disease; (iii) oCRS resulting from dental implants disorders can frequently be characterized as a CRS with a rich tissue eosinophilic component.

Preoperative Sinonasal Computed Tomography Score in Chronic Rhinosinusitis with Nasal Polyps.

This study investigated the relationship between sinonasal inflammatory involvement according to the computed tomography (CT) staging system (Lund-Mackay score) with clinical, laboratory, histopathological and prognostic features of chronic rhinosinusitis with nasal polyps (CRSwNP). Seventy-eight patients with CRSwNP who had undergone surgery were enrolled. Total (p = 0.0062), ethmoid (p = 0.0496), sphenoid (p = 0.0335), ostiomeatal complex (OMC) (p = 0.0235) and frontal (p = 0.0164) CT scores were predictive of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD) in the univariate analysis. Total (p = 0.0022), ethmoid (p = 0.0290), sphenoid (p = 0.0370), frontal (p = 0.0116), maxillary (p = 0.0357) and OMC (p = 0.0058) CT scores were predictve of asthma at the univariate analysis. No significant differences were found between patients with vs. without allergy in terms of total and partial CT scores. High blood eosinophil counts (>0.24 vs. ≤0.24 cells × 109/L) resulted in being associated with total (p = 0.0213), maxillary (p = 0.0227) and ethmoid (p = 0.0491) CT scores in the univariate analysis. Higher ethmoid (p = 0.0006) and total sinonasal (p = 0.0027) CT scores were found to predict histopathologically eosinophil CRSwNPs in the univariate analysis. CT scores did not result as predictive of NSAID-exacerbated respiratory disease, asthma, or blood eosinophil count at the multivariate analysis. Risk of relapse was related to the presence of NERD (p = 0.0207, HR [95% CI] 3.914 [1.232-12.435]), higher preoperative total (HR = 1.098 95%CI: 1.001-1.204, p = 0.0486) and frontal sinus CT scores (HR = 1.555 95%CI: 1.006-1.886, p = 0.0218), but these results were not confirmed by the multivariable analysis. Sinonasal CT scores showed significant differences in this heterogeneous inflammatory condition. Identifying CRSwNP characteristics is necessary to avoid generic treatments with poor outcomes.

Sex and age-related differences in chronic rhinosinusitis with nasal polyps electing ESS.

PURPOSE: Sex and age of patients are variables affecting across the board all chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes. The main aim of this investigation was to compare the clinical, laboratory, pathological and prognostic characteristics of CRSwNP in male vs female patients stratified according to age (young-adult [20 years ≤ age ≤ 40 years], and elderly [age ≥ 65 years]). This is the first study that analyzed the association of the above-mentioned features with age and sex combination in CRSwNP electing endoscopic sinus surgery (ESS). MATERIALS AND METHODS: One hundred and five consecutive young-adult patients (62 males and 43 females) and 67 elderly patients (44 males and 23 females) with CRSwNP who had undergone ESS were enrolled. RESULTS: The recurrence rate resulted associated with the age and sex combination (p = 0.0165). Young-adult males' recurrence rate (29.0%) was higher than young-adult females (11.6%) and elderly males (4.5%). Allergy resulted associated with age and sex combination (p = 0.0158). Young-adult males' allergy rate (50.0%) was higher than elderly males' (29.5%) and elderly females' (13%). Moreover, allergy rate was higher in young-adult females (41.9%) than in elderly females. CONCLUSION: Our data suggest the possibility of an interaction between sex and age in the recurrence of nasal polyposis after ESS. More studies are needed to understand the role of sex hormones in pathogenesis and prognosis of CRSwNP.

The Effect of Isotonic Saline Nasal Lavages in Improving Symptoms in SARS-CoV-2 Infection: A Case-Control Study.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly colonizes nasopharynx. In upper airways acute infections, e.g., the common cold, saline nasal irrigations have a significant efficacy in reducing symptoms. The present study aimed to test the efficacy of nasal lavages in upper airways symptoms of Coronavirus Disease 2019 (COVID-19). Methods: A series of consecutive adult subjects who tested positive for SARS-CoV-2 from December 2020 to February 2021 performed daily nasal lavages with saline solution (Lavonase®-Purling, Lugo di Romagna, Italy) for 12 days, starting on the day after the SARS-CoV-2 positive swab. A control group included a historical series of patients who were infected in February-March 2020 and who did not perform lavages. An ad hoc questionnaire regarding symptoms was administered to each subjects at base-line and 10 days after diagnosis (i.e., on the same day of the control swab) in both cases and controls. Results: A total of 140 subjects were enrolled. 68 participants in the treatment group and 72 in the control group were included. 90% of respondents declared the lavages were simple to use and 70% declared they were satisfied. Symptoms of blocked nose, runny nose, or sneezing decreased by an average of 24.7% after the treatment. Blocked nose and sneezing increased in the same period of time in the control group. Ears and eyes symptoms, anosmia/ageusia symptoms, and infection duration (10.53 days in the treatment group and 10.48 days in the control group) didn't vary significantly among the two groups. Conclusion: Nasal lavages resulted to significantly decrease nasal symptoms in newly diagnosed SARS-CoV-2 patients. These devices proved to be well-tolerated and easy to be used. Further studies on a larger number of subjects are needed in order to possibly confirm these preliminary results.

Middle turbinate handling during ESS. Our experience.

PURPOSE: The treatment of middle turbinate (MT) during endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) remains a controversial issue. Several authors recommended preservation of MT to avoid complications, but MT resection is sometimes necessary. In the last years, our group has applied an original surgical technique to preserve MT, stabilize its head and ensure patency of the ostiomeatal complex (OMC) in ESS. We herein described this approach to the MT and reported its preliminary results in terms of post-operative endoscopic features and complications. METHODS: The study retrospectively considered 34 consecutive adult patients suffering from CRS and treated with primary or revision ESS. Medialization of the MT and its stabilization to achieve post-operative patency of the OMC was obtained by means of: (i) creation of a surgically controlled synechia between the MT head and nasal septum; (ii) positioning of a silicone plate in the OMC. The silicone splints kept the MT head in an obliged position to contact the septum. RESULTS: At 12-month follow-up control, we found: (i) stabilized MT medialization in all treated cases, (ii) only one case of lateral synechia without recurrent CRS, and (iii) a polypoid recurrence rate of 13%. CONCLUSIONS: The MT handling technique during ESS herein preliminarily described seems to be an effective approach to medialize and stabilize the MT. This technique could be particularly appropriate for unstable MT after removing massive inflammatory lesions of the mucosa.

Blood Eosinophilic and Basophilic Trends in Recurring and Non-Recurring Eosinophilic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Very few studies have compared blood eosinophil and basophil levels before and after surgery in patients with eosinophilic CRSwNP (eCRSwNP). No investigations seem to have repeatedly measured them pre- and postoperatively in eCRSwNP patients with recurring versus non-recurring disease to examine how their levels evolved. OBJECTIVE: Hence this study to analyze blood eosinophil and basophil levels in patients with eCRSwNP immediately before surgery and afterwards, at 4 months, 1 year, and then yearly up to 5 years. METHODS: Fifty-one eCRSwNP patients were enrolled, who all had preoperative laboratory data and the results of at least 4 of the 6 scheduled postoperative follow-up tests. RESULTS: Seventeen patients had recurrent disease. Blood eosinophil counts (p = 0.005) and percentages (p = 0.002) were both higher in these patients than in those whose eCRSwNPs did not recur after surgery. Blood basophil counts (p = 0.04) and percentages (p < 0.05) were also significantly higher in patients whose eCRSwNPs relapsed. The time by relapse interaction was not significant for either counts or percentages, though an effect of time was detected for basophil counts (p = 0.01). CONCLUSIONS: In eCRSwNP, the statistical analysis of repeated quantitative laboratory data can shed light on the evolution of a patient's systemic inflammatory picture in response to previous treatments, and above all to long-term therapies. Long-term monitoring of blood eosinophil and basophil levels could be of significant value when monoclonal antibodies that inhibit IL signaling will widely enter in clinical practice for eCRSwNP treatment to follow the effectiveness of therapy over time.

Neutrophil infiltrates and eosinophil aggregates in chronic rhinosinusitis with nasal polyps and EGPA.

INTRODUCTION/OBJECTIVES: The histopathological study of inflammatory cells and their tendency to form aggregates in chronic rhinosinusitis with nasal polyps (CRSwNP) has shown promising results in determining the pathogenesis and predicting clinical outcome. Bilateral nasal polyps also occur in over 70% of patients with eosinophilic granulomatosis with polyangiitis (EGPA). The study aim was to investigate neutrophil infiltrates and eosinophil aggregates in CRSwNP and EGPA tissues of Caucasian patients. METHOD: A histopathological study was performed on surgical specimens of nasal polyps from 144 adults (15 with allergic fungal rhinosinusitis; 19 with nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD); 16 with intrinsic asthma; 21 with extrinsic asthma; 21 with allergy; 22 with eosinophil CRSwNP (ECRSwNP); 17 with non-ECRSwNP; 13 with EGPA). RESULTS: Focusing on the presence of tissue eosinophil aggregates, NERD and ECRSwNP were the sub-cohorts with the highest rate. Neutrophil infiltrate rate was significantly higher in EGPA sub-cohort than in all CRSwNP sub-cohorts apart from non-ECRSwNP. CONCLUSIONS: Structured histopathology is increasingly identifying the different histotypes of CRSwNP. This analysis can be used to better understand CRSwNP endotypes and develop targeted therapies. The response to therapy and therefore control of CRSwNP relapses definitely depends on our ability to act on the underlying inflammatory pattern. Key points • Systematic analysis of how neutrophil infiltrates and eosinophilic aggregates are distributed in the different phenotypes of CRSwNP and EGPA. • Neutrophil infiltrates and eosinophil aggregates are strong risk factors for nasal polyps' refractoriness. • NERD and ECRSwNP are the sub-cohorts of CRSwNP with the highest rate of tissue eosinophil aggregates. • Neutrophil infiltrates are significantly higher in EGPA.

Nasal polyps in eosinophilic granulomatosis with polyangiitis: Structured histopathology and CD105 expression.

PURPOSE: Distinguishing the prodromal nasal polyposis of eosinophilic granulomatosis with polyangiitis (EGPA) from chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenge for rhinologists and rheumatologists. It has recently been reported that angiogenesis and CD105 expressed on vascular endothelial cells could have a role in the pathogenesis and development of nasal polyps. This exploratory study examined the structured histopathology of nasal polyps in patients with EGPA and CRSwNP, comparing CD105 expression in their nasal tissue with that of a control group with no chronic sinonasal inflammation. METHODS: A structured histopathological study was performed on surgical specimens of nasal tissue from 32 adults (13 with EGPA, 14 with CRSwNP, 5 controls), considering CD105 as a marker to determine microvessel density (MVD). RESULTS: The mean eosinophil count was higher in EGPA patients with tissue inflammation (p = .002), and in CRSwNP patients with sub-epithelial edema (p = .009). Neutrophil infiltration was significantly associated with severe tissue inflammation in EGPA patients (p = .04), but with the absence of fibrosis in CRSwNP patients (p = .04). In the EGPA group, CD105-MVD correlated with tissue eosinophil count (p = .05). Mean CD105-MVD was significantly higher in EGPA patients with mucosal ulceration (p = .004). In the CRSwNP group, a CD105-MVD correlated positively and significantly with tissue eosinophil count (p = .01). CONCLUSION: Alongside the known abundance of eosinophils, other cells might contribute to inflammatory processes. Neutrophils may amplify inflammation, eosinophil recruitment and tissue damage. CD105 expression in CRSwNP and EGPA nasal polyps supports the hypothesized involvement of angiogenesis in the pathogenesis and development of nasal polyps.

Postoperative radiotherapy for laryngeal cancer. The prognostic role of programmed death-ligand 1: An immune microenvironment-based cluster analysis.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression and the tumor's immune microenvironment has yet to be investigated in the specific setting of adjuvant postoperative radiotherapy (PORT) for laryngeal carcinoma (LSCC). The main aim of this exploratory study was to investigate, also by cluster analysis, whether PD-L1 expression (in terms of combined positive score [CPS]), tumor-infiltrating lymphocytes (TIL), and tertiary lymphoid structures (TLS) correlated prognostically with response to PORT in a cohort of consecutive LSCC patients. METHODS: PD-L1, TIL and TLS were assessed in 24 consecutive patients with LSCC who underwent PORT. Cluster analysis was used to classify cases on the strength of these parameters. RESULTS: A CPS ≥ 1 was associated with a significantly lower recurrence rate (p = 0.033), and longer disease-free survival (DFS) (p = 0.012) than a CPS < 1. Two clusters of prognostic relevance emerged from our analysis. Cluster 1 was characterized by a mean CPS of 23.0 ± 37.9, a mean TIL count of 68.0 ± 16.4, and the presence of TLS in all cases. Cluster 2 featured a mean CPS of 3.1 ± 7.3, a mean TIL count of 23.9 ± 16.5, and no cases with TLS. Cluster 1 showed a trend towards a lower recurrence rate (p = 0.071) and longer DFS (p = 0.054) than cluster 2. CONCLUSIONS: Judging from this preliminary investigation, assessing PD-L1 and immune microenvironment markers seems a promising approach for identifying patients at higher risk of LSCC recurrence after PORT, who might reasonably benefit from adjuvant postoperative chemo-RT, or immunotherapy.

Prognostic Significance of CD105- and CD31-Assessed Microvessel Density in Paired Biopsies and Surgical Samples of Laryngeal Carcinoma.

Small pretreatment laryngeal biopsies may not fully represent a tumor's biological profile. This study on laryngeal squamous cell carcinoma (LSCC) aimed to investigate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in paired biopsies and surgical specimens and the association and discrepancy between CD105- and CD31-assessed MVD in biopsies and surgical specimens. CD105- and CD31-assessed MVD was analyzed in paired biopsies and surgical specimens of 45 consecutive cases of LSCC. In the LSCC biopsies and surgical specimens, median CD105-assessed MVD was significantly higher in N+ than in N0 cases (p = 0.0008, and p = 0.0002, respectively). Disease-free survival (DFS) was associated with CD105- and CD31-assessed MVD in both biopsies and surgical specimens (p < 0.0001 for all specimens). Multivariable Cox's regression showed that pathological grade (p < 0.0001) and CD105-assessed MVD in LSCC biopsies (p = 0.0209) predicted DFS. Lin's concordance coefficient showed that CD31 overestimated MVD compared with CD105 in LSCC biopsies and surgical specimens. CD105-assessed MVD should be further investigated in larger LSCC series as a potential prognostic marker for identifying: patients at higher risk of recurrence who might warrant more aggressive therapy; and cN0 patients requiring elective neck dissection for a significant risk of regional metastasis.

Biological tumor markers (maspin, CD105, nm23-H1) and disease relapse in laryngeal cancer: cluster analysis.

BACKGROUND: The aim of this investigation was to see if a panel of biomarkers (maspin, CD105, and nm23-H1) could be used to stratify patients with laryngeal squamous cell carcinoma (LSCC) in homogeneous disease recurrence risk clusters. METHODS: Cluster analysis was used to classify 89 patients based on their immunohistochemical expression of nm23-H1, CD105, and maspin. RESULTS: Our analysis identified seven homogeneous clusters: the LSCC recurrence rate was lowest in cluster 6 (non-nuclear maspin pattern, nuclear nm23-H1 expression ≥10%, endothelial CD105 expression <6%; P = .009), and highest in cluster 3 (non-nuclear maspin pattern, nuclear nm23-H1 expression <10%, endothelial CD105 expression ≥6%; P <.001). CONCLUSIONS: Similar panels of biological variables identified by cluster analysis should be tested in prospective clinical trials to establish whether treating patients identified as being at higher risk of LSCC recurrence more aggressively could significantly improve their recurrence rate and/or disease-specific survival.

Maspin expression and anti-apoptotic pathway regulation by bcl2 in laryngeal cancer.

OBJECTIVES: Comprehension of the interplay of pro-apoptotic and anti-apoptotic stimuli in laryngeal squamous cell carcinoma (LSCC) is crucial to understand tumor development, biological behavior and treatment response. Bcl-2 family proteins mainly regulate the apoptotic signal cascade. In some cancers, maspin seems to influence the balance between pro-apoptosis and anti-apoptosis bcl-2 family proteins. The aim of this study was to investigate the potential relationship between bcl-2 anti-apoptotic factor and the tumor suppressor maspin in LSCC. MATERIALS AND METHODS: 31 consecutive patients who underwent primary surgery and post-operative radiotherapy for LSCC were evaluated retrospectively. For each case, immunohistochemistry assays for bcl-2 and maspin were performed. Data were also collected on N-status, pT stage, grading, recurrence and disease-free survival (DFS). RESULTS: Patients with nuclear maspin pattern of expression showed a significantly lower recurrence rate (p = 0.04) and longer DFS (p = 0.0018). The expression of bcl-2 was not associated with recurrence rate or DFS either in the whole cohort or in cases with nuclear maspin pattern, while in patients with non-nuclear maspin pattern, a statistical trend was found toward a shorter DFS for bcl-2 positive cases (p = 0.062). In the multivariate model, only maspin expression pattern retained its independent prognostic significance (p = 0.006). CONCLUSIONS: Nuclear maspin pattern seemed to be an independent positive prognostic factor, while bcl-2 prognostic value was related to maspin expression pattern. Further investigations are needed to support the use of bcl-2 inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.

Expression of maspin tumor suppressor and mTOR in laryngeal carcinoma.

PURPOSE: The main aim of this study was to conduct a preliminary investigation into the possible relationship between mTOR and the nuclear tumor suppressor maspin in laryngeal carcinoma (LSCC). MATERIALS AND METHODS: mTOR expression and maspin pattern were ascertained, also with the aid of image analysis in 79 consecutive LSCCs. RESULTS: Considering the whole series, univariate statistical analysis identified significant differences in the distributions by lymph node status (N0 vs N+) between two subgroups of patients with and without loco-regional carcinoma recurrences (p = 0.017). The log-rank test also showed a shorter disease-free survival (DFS) in pN+ patients (p = 0.0008). mTOR expression was significantly higher in patients whose disease recurred (p = 0.009). The DFS rate was also significantly shorter in cases of LSCC with an mTOR expression ≥11.55% (p = 0.049). Multivariate analysis showed that N status (p = 0.002) and mTOR expression (p = 0.037) retained their prognostic significance in relation to cancer recurrence. In a subgroup of LSCCs with a non-nuclear maspin pattern, mTOR expression was significantly higher in patients whose disease recurred. Multivariate analysis disclosed that N stage (p = 0.012) retained its independent prognostic significance for disease recurrence in this setting. mTOR expression showed a trend towards independent significance in terms of carcinoma recurrence (p = 0.083). CONCLUSIONS: mTOR inhibitors seem promising for use in cancer therapies. Further investigations are needed on the prospects of incorporating modern mTOR inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.