Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance

IntroductionHuman papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx.ObjectiveWe aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study.MethodsThis retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined.ResultsPolyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p = 0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years.ConclusionThe close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques.     

Preservación de órgano en pacientes con tumores avanzados de laringe. Resultados de la quimioterapia de inducción versus quimio-radioterapia en la práctica clínica real

Introduction and objectivesA high percentage of patients with locally advanced larynx carcinomas are candidates for inclusion in organ preservation protocols. The objective of this study is to compare the results of two schemes of preservation, induction chemotherapy versus chemoradiotherapy, in patients with locally advanced larynx carcinomas in the context of actual clinical practice.MethodsOur retrospective study included 157 patients with locally advanced tumours of the larynx (T3-T4) treated with induction chemotherapy (n = 121) or chemoradiotherapy (n = 36).ResultsFrom 121 patients who began treatment with induction chemotherapy, 6 died due to toxicity, 37 were treated with surgery, and 78 completed the preservation scheme; 36 patients received treatment with chemoradiotherapy. There were no significant differences in 5-year disease-specific survival between both treatments: 68.9% in induction chemotherapy versus 75.7% in chemoradiotherapy (p = 0.259). In 45.9% of patients the laryngeal function was preserved. Patients treated with chemoradiotherapy had a tendency to have better 5-year laryngeal dysfunction-free survival than patients treated with induction chemotherapy (55.6% versus 44.8%, p = 0.079).ConclusionPatients included in a protocol of organ preservation achieved a 5-year laryngeal dysfunction-free survival of 45.9%. There were no significant differences in disease-specific survival among patients treated with induction chemotherapy or chemoradiotherapy.     

Correlation between vascular endothelial growth factor expression and presence of lymph node metastasis in advanced squamous cell carcinoma of the larynx

IntroductionSquamous cell carcinoma is the most common neoplasm of the larynx, and its evolution depends on tumor staging. Vascular endothelial growth factor is a marker of angiogenesis, and its expression may be related to increased tumor aggressiveness, as evidenced by the presence of cervical lymphatic metastases.ObjectivesTo evaluate the expression of the vascular endothelial growth factor marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4) and correlate it with the presence of cervical lymph node metastases.MethodsRetrospective clinical study and immunohistochemical analysis of vascular endothelial growth factor through the German scale of immunoreactivity in products of non-glottic squamous cell carcinomas.ResultsThis study analyzed 15 cases of advanced non-glottic laryngeal tumors (T3/T4), four of which exhibited cervical lymphatic metastases. There was no correlation between vascular endothelial growth factor expression and the presence of cervical metastases.ConclusionAlthough vascular endothelial growth factor was expressed in a few cases, there was no correlation with the spread of cervical lymph metastases.     

Impact of treatment modality on survival in patients with stage IV laryngeal cancer: A population-based propensity score analysis.

IntroductionThe treatment of advanced stage laryngeal suffered a major shift away from surgery and towards larynx-preservation alternatives after the publication of major clinical trials. But its applicability in real-world situations is not consensual.Materials and methodsWe reviewed a population-based database from Brazil regarding patients treated for laryngeal cancer and selected those with stage IV disease at presentation. Survival analysis was realized by the Cox proportional hazards method and propensity scores were used to compensate for non-random allocation to different treatment arms.ResultsA total of 5577 patients were included in the analyses, with 4243 staged as CS IVa, 1010 as CS IVb and 324 as CS IVc. In univariate and multivariate analysis, gender, cT stage, cN stage, cM stage and treatment modality were significant predictors of disease-specific survival. In patients with CS IVa, age, gender, payment modality, location within the larynx, cT and cN stages and treatment modality were significant. After propensity score adjustment, treatment modality remained significant, favoring primary surgery with disease-specific survival (HR: 0.5041, 95% CI: 0.4494–0.5644, p < 0.001) and overall survival (HR: 0.5485, 95% CI: 0.4955–0.6072, p < 0.001) as outcomes of interest. Patients staged as cT4a cN0 were selected and analyzed as a distinct subset. In multivariate analysis, treatment modality was the only variable with significant prognostic impact with improved outcome for surgery-based treatment (HR: 2.521, 95% CI: 1.897–3.350, p < 0.001).ConclusionsThe extrapolation of clinical trials to the real-world facilities must be carefully weighted. The setting of trial conduction may influence its outcome and may not be reproducible. Our results show that patient selection and the facilities of clinical trials may play a significant role in the success of non-surgical approaches to non-metastatic stage IV laryngeal cancer.     

The role of red cell distribution width in the locoregional recurrence of laryngeal cancer

IntroductionAlthough the red cell distribution width has been reported as a reliable predictor of prognosis in several types of cancer, to our knowledge few reports have focused on the prognostic value of red cell distribution width in laryngeal carcinoma.ObjectiveWe aimed to explore whether the pretreatment red cell distribution width predicted recurrence in laryngeal cancer patients is a simple, reproducible, and inexpensive prognostic biomarker.MethodsAll laryngeal cancer patients who underwent curative surgery (n = 132) over a 7 year study period were evaluated. Data on demographics, primary tumor site, T-stage, N-stage, histological features (differentiation; the presence of perineural/perivascular invasion), treatment group (total laryngectomy or partial laryngectomy) or adjuvant therapy (chemotherapy/radiotherapy); laboratory parameters (complete blood count, including the pre-operative red cell distribution width), and disease-free survival rates were retrospectively reviewed. All cases were divided into three groups by the red cell distribution width tertile [<13% (25th percentile) (n = 31), 13–14.4% (50th percentile) (n = 72), and >14.4% (75th percentile) (n = 29)].ResultsHigh-red cell distribution width group included more patients of advanced age, and more of those with recurrent and metastatic tumors (p = 0.005, 0.048, and 0.043, respectively). Individuals with red cell distribution width >14.4% (75th percentile) had lower disease free survival rates than did those with red cell distribution width <13% (25th percentile) (p = 0.014). Patients with red cell distribution width >14.4% at diagnosis were at a higher risk of locoregional recurrence (hazard ratio = 5.818, 95% confidence interval (95% CI) 1.25–26.97; p = 0.024) than patients with a normal red cell distribution width (<13%).ConclusionWe found that the pretreatment red cell distribution width was independently prognostic of disease free survival rate in patients with laryngeal cancer and may serve as a new, accurate, and reproducible means of identifying early-stage laryngeal cancer patients with poorer prognoses.     

MMP-2 expression in 102 patients with glottic laryngeal cancer

In order to evaluate the potential of matrix metalloproteinase 2 (MMP-2) as a prognostic factor for glottic laryngeal cancer. One hundred and two surgical specimens from patients with glottic laryngeal cancer who underwent laryngectomy for their disease in the University Hospital of Patras, Greece from 1998 to 2005 were reviewed retrospectively regarding MMP-2 expression via immunohistochemistry. Immunostaining was performed using a streptavidin–biotin peroxidase complex technique (LSAB). Results revealed that 54 of 102 patients (52.9%) had positive cytoplasmic staining for MMP-2. Kaplan–Meier analysis demonstrated statistically significant difference (p = 0.037) for the 5-year overall survival rate between the groups with positive and negative MMP-2 expression, and marginal statistical significance for the disease free survival rate (p = 0.048). The capsule rupture of metastatic lymph nodes and MMP-2 expression in primary tumor site also seems to be related (p = 0.047). Statistical significance could not be established between MMP-2 expression and the clinicopathological features of the disease (T stage, N stage, clinical stage, differentiation). In conclusion, MMP-2 expression was related with worse overall and disease-free survival and could be considered as a potential marker of poor prognosis.     

Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation

OBJECTIVES/HYPOTHESIS: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. STUDY DESIGN: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. METHODS: To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. RESULTS: The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. CONCLUSIONS: The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.     

Otorhinolaryngologists’ personal treatment preferences (total laryngectomy or laryngeal preservation) when faced with advanced stage laryngeal cancer

ObjectiveTo analyse the treatment options that otorhinolaryngologists would consider if faced with advanced stage laryngeal cancer amenable to total laryngectomy or an organ preservation protocol.Material and methodsProspective study conducted in a French Teaching Hospital based on questionnaires filled in by 163 otorhinolaryngologists in 2012, studying the percentage chance of cure that they would be prepared to trade-off to preserve their larynx, defining the additional information that they would like to receive and identifying any statistical associations between these parameters and various medical and socioeconomic variables.ResultsA total of 42.3% of otorhinolaryngologists would not consider the slightest trade-off to preserve their larynx and preferred to undergo total laryngectomy. In the group of otorhinolaryngologists who would consider a larynx preservation protocol (57.6%), the percentage chance of cure that they would be willing to trade-off to preserve their larynx ranged between 5 to 100% (median: 15%) and 4.2% of them were willing to trade-off all chances of cure (100%) to avoid total laryngectomy. The percentage of otorhinolaryngologists who would not consider trading off the slightest chance of survival to preserve their larynx increased from 29.3 to 49.5% (P = 0.01) when they participated in multidisciplinary consultation meetings. In the group of otorhinolaryngologists who would consider a larynx preservation protocol, the median percentage survival trade-off that they would consider in order to preserve their larynx (i) decreased from 20 to 10% (P = 0.004) when they participated in multidisciplinary consultation meetings and (ii) increased regularly with their number of years of practice (P = 0.03) and their age (P = 0.025). Finally, 25.1% of otorhinolaryngologists wanted to receive additional information, although none of the variables analysed affected this desire for more information.ConclusionTreatment options considered by otorhinolaryngologists faced with advanced stage laryngeal cancer were almost equally divided between total laryngectomy and larynx preservation. Number of years of practice and regular participation in head and neck cancer multidisciplinary consultation meetings were variables that significantly influenced this choice.     

Total laryngectomy or laryngeal preservation for advanced laryngeal cancer. Impact of the functional risk upon the patient's preferences

ObjectiveTo analyse, based on an anonymous questionnaire, the treatment decision envisaged and the impact of the medical information delivered in patients facing the diagnosis of an advanced laryngeal cancer amenable to total laryngectomy or a laryngeal preservation protocol.Material and methodsProspective study conducted in a French teaching hospital based on questionnaires filled in by 269 patients attending the otorhinolaryngology clinic.ResultsA total of 28.6% of patients would not consider any trade-off of cure to preserve their larynx; 1.4% of patients were willing to trade all chances of cure in order to avoid total laryngectomy. The median percentage of cure that patients were ready to loose in order to preserve their larynx was 33% (range: 5 to 100%); 47.9% of patients wanted to receive additional information before making their decision with a significant increase among patients with a level of education beyond secondary school (P = 0.0006) and among patients with a family history of cancer (P = 0.038). The additional information most frequently requested concerned the complications related to the laryngeal preservation protocol (34.1%) and the cure rate (28.6%). After receiving information about the risk of tracheostomy and permanent gastrostomy following the laryngeal preservation protocol, the percentage of subjects who would not consider any trade-off in order to preserve their larynx increased to 31.2% and 56.1%, respectively.ConclusionLaryngeal preservation is not a major objective of treatment shared by patients filling a questionnaire devoted to the choice of treatment when facing an advanced laryngeal cancer. Specific information concerning the expected results and the inherent risks involved in the various treatment options must be provided in every case.     

Debulking obstructing laryngeal cancers to avoid tracheotomy

IntroductionUpper airway obstruction, secondary to neoplasms presenting with stridor, is traditionally treated by tracheostomy. However, this common procedure can potentially have an impact on the long-term outcome, with tumor implantation into the tracheostomized wound leading to peristomal recurrence after laryngectomy, with the risk of stomal recurrence.ObjectiveTo describe our clinical experience with tumor debulking as an alternative treatment choice of tracheotomy in patients with advanced larynx cancer at a tertiary referral center.MethodsA retrospective chart review of 87 subjects who had advanced larynx cancer (T3/4) with airway obstruction from our institutional database was conducted. Medical records including demographics, daily notes during hospitalization, and operative notes were used for clinical data of patients. The strategy for maintaining the airway patency was tracheotomy (emergency or awake) and tumor debulking (laser or coblation). Endophytic and exophytic laryngeal tumors were also noted.ResultsIn 41/87 (47.1%) patients, a tracheotomy was performed as an initial treatment (11 were emergency, 30 were planned) to maintain airway patency. Tumor debulking was performed in 28 exophytic and 18 endophytic lesions by laser or coblation (17 and 29 patients, respectively). Tracheotomy was performed in 5 patients (4 endophytic, 1 exophytic) who could not tolerate debulking surgery due to aspiration, edema and dyspnea. Three of the them who required subsequent tracheotomy was in the laser group and two in the coblation group. The success rate of laser debulking was 82.35% (14/17) and 93.1% (27/29) for coblation.ConclusionTumor debulking is a safe and effective method to avoid awake tracheotomy in patients suffering from airway obstruction due to advanced larynx cancer.     

基质金属蛋白酶14基因在人喉鳞状细胞癌中表达差异的分析

OBJECTIVE: To investigate the role of expression of matrix mettallo-proteinase 14 (MMP14) in laryngeal carcinomas and the relationship between MMP14 expression and the laryngeal biological behavior. METHODS: The gene expression differences of MMP14 between fresh laryngeal cancer tissues and their surrounding normal mucosa was analyzed by RT-PCR. The expression of MMP14 protein in paraffin-embedded tissues was determined immunohistochemically. All statistical analyses were performed by SPSS version 10.0. RESULTS: In the 33 cases of matched specimens, MMP14 gene expression was much higher in tumor tissues than that in surrounding ing normal tissues in 26 cases and lower in 2 cases, whereas in other 5 cases, no significant difference was observed between the cancer tissue and the surrounding normal tissue. MMP14 gene expression was not different in different stages in laryngeal glottic cancers, but correlated to the differentiation and lymph node metastasis (P < 0.05). There was correlation between MMP14 gene expression and the stage, differentiation and lymph node metastasis in the laryngeal supraglottic cancers (P < .05). MMP14 protein was localized predominantly in the carcinoma cell cytoplasm and in the stromal fibroblasct cytoplasm, and weakly or not expressed in surrounding normal tissue. MMP14 protein expression was much higher in tumor tissue than that in surrounding normal tissue in most of the cases. In general, MMP14 protein expression was the same as MMP14 gene expression and related to the stage, differentiation and lymph node metastasis in the laryngeal cancers. There was no survival difference at 3, 5 and 7-year between the group with higher MMP14 protein expression in tumor tissues than surrounding normal tissues and the group with no difference of MMP14 protein expression (Log Rank, P=0.5535). CONCLUSIONS: The protein MMP14 may play role in laryngeal cancer invasion in a certain extent, but important role in lymph node metastasis of laryngeal cancer. The over-expression of MMP14 protein may be a marker for lymph node metastasis of laryngeal cancer.     

Long-term trends in gender,T-stage,subsite and treatment for laryngeal cancer at a single center

To investigate the changes in the epidemiology of laryngeal squamous cell carcinoma (LSCC) regarding gender, T-stage and subsite distribution, and to identify the potential effect of introducing new therapeutic alternatives for early and advanced stage LSCC. A prospective cohort study of LSCC patients diagnosed and treated at a single tertiary referral center in Norway. Retrospective analysis of prospectively recorded data from 1,616 patients treated for LSCC in all subsites of the larynx during 1983–2010. Females represented an increasing proportion of cases throughout the study (p < 0.01) and presented more often than men with supraglottic cancer (p < 0.01). Marked changes in the distribution of T-stages over time were observed in both early and advanced stage LSCC. T1a glottic tumors constituted 56 % of all early-stage LSCC and were predominantly treated by transoral endoscopic laser surgery. The introduction of chemoradiotherapy for advanced stage LSCC offers a distinct advantage for laryngeal preservation. The increasing proportion of females with LSCC may be explained by changes in smoking habits. The proportion of T1a glottic LSCC gradually increased over time, while T4 supraglottic LSCC became less frequent. Videostroboscopy should be considered mandatory in the diagnosis and follow-up of LSCC. Transoral laser microsurgery is the standard first-line treatment for T1a glottic tumors. Chemoradiotherapy has reduced the number of total laryngectomies and is now regarded as the primary treatment for advanced stage tumors.     

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center

IntroductionEven with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered.ObjectiveTo review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution.Material and methodsWe studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone.Results796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1–16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival.ConclusionThe present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.     

The prognostic value of proliferating cell nuclear antigen (PCNA) in the advanced cancer of larynx

It was retrospectively examined whether the tumor growth fraction determined by PCNA score in the advanced cancer of larynx could be used as a prognostic factor. There was used immunohistochemical method to evaluate the PCNA score of positive cells in paraffin embedded tissues of laryngeal carcinoma obtained from 90 patients. They were treated by surgery in the Department of Otolaryngology at the Medical University in Cracow, Poland in 1987 and 1988. The follow-up period was not shorter than 5 years. In the examined material there were 59 patients with tumor T3 and 31 with T4. Neck dissection on one or on both sides was performed on patients. The metastases in regional lymph nodes was found in 26 patients. Histologic grading (G1=18, G2=52 and G3=20 patients) and number of mitosis was assessed. The PCNA score was defined by counting positive cells and presented as percentage of a cells. It ranged from 2.1 to 73.0% with the average value of 34.5%. The PCNA score below this level was defined as a low PCNA score (49 patients) and above this level as a high PCNA score (41 patients). There was a correlation between PCNA score and survival of the patients. 35 patients (71.4%) with low PCNA score survived and 15 (36.6%) with high PCNA score (P<0.05). Similarly the high PCNA score influenced the number of metastases in lymph nodes. They occurred in low and high PCNA score respectively at nine (18.4%) and 17 patients (41.5%) (P<0.05). There was not found any correlation between PCNA score and tumor differentiation, its size and mitosis number. The PCNA may be a prognostic factor for the patients with advanced cancer of larynx.     

Expresión de E-cadherina y β-catenina en carcinomas de células escamosas de laringe e hipofaringe

Introduction and objectivesDysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development.The aim of this paper is to investigate the prognostic significance of E-cadherin and β-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas.Material and methodsTumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005.E-cadherin and β-catenin expression was analysed by immunohistochemistry, quantifying the percentage of stained cells and the intensity of staining.ResultsE-cadherin and β-catenin expression was evaluable in 59 laryngeal carcinomas and in 58 cases of hypopharyngeal carcinomas.In the laryngeal tumours, a significant association was found between the low expression of membrane β-catenin with T4 tumours and tumour recurrence. In the hypopharynx there was a significant association between positive expression of nuclear β-catenin and poor histological differentiation (P = .02). In the multivariate analysis, only the presence of lymph node metastases was an independent predictive factor of decreased disease-specific survival in laryngeal squamous cell carcinomas.ConclusionsThe expression of E-cadherin and β-catenin does not show prognostic significance in laryngeal and hypopharyngeal squamous cell carcinomas over the TNM classification.     

Surgical options in radiotherapy-failed early glottic cancer

After failure of curative radiotherapy (RT), surgery is the main therapeutic option to control recurrent laryngeal cancer. Recurrences after RT for T1–T2 tumours of the glottic larynx are often diagnosed at a more severe stage than the original disease and, thus, usually treated by radical approaches. Our aim is to investigate the feasibility of more conservative strategies for proper treatment of post-RT recurred glottic cancer. We collected and reviewed our files from 1990 to 2006, selecting 75 patients which matched the following inclusion criteria: (1) patient was originally diagnosed with early stage squamous cell carcinoma of the glottic larynx (stage I–II according to 2010 TNM), (2) patient was treated by RT with curative intent, (3) patient presented a recurrence of disease after RT which was surgically treated at our Institution. T stage at first diagnosis was T1a in 41 cases (55 %), T1b in 12 (16 %) and T2 in 22 (29 %). At clinical examination of RT-recurred lesions, we documented advanced lesions (rT3–rT4) in 29 out of 75 patients (39 %). Overall, an upstage was reported for 56 % RT-recurred cancers, while 37.3 % remained at the same stage than the original tumour and 6.7 % were downstaged. Twelve patients (16 %) underwent salvage partial laryngectomy (SPL), while 63 (84 %) received a salvage total laryngectomy (STL). Multivariate analysis showed that rTNM according to the AJCC-UICC of 2010 was the only prognostic factor for both disease-free survival (p = 0.042) and overall survival (p = 0.004). Considering the prognostic impact of rT and rN we documented a statistical significance only in terms of overall survival for both factors (p = 0.004 and p = 0.04, respectively). Although STL remains the most frequent treatment choice for failures after RT in laryngeal carcinomas, SPL represents a valid option for selected patients with limited recurrence and can deliver good oncologic and functional results if performed according to careful indications.     

程序性细胞死亡因子4在喉鳞状细胞癌中的表达及其与肿瘤细胞增殖和凋亡的关系

目的:探讨喉鳞状细胞癌中程序性细胞死亡因子4(PDCD4)蛋白表达与肿瘤细胞增殖和凋亡的关系及其临床意义。方法:采用免疫组织化学技术检测60例喉鳞状细胞癌组织及21例正常喉黏膜上皮组织中PDCD4和Ki-67的表达,原位末端标记(TUNEL)法检测细胞凋亡,以细胞增殖指数(PI)和细胞凋亡指数(AI)表示增殖与凋亡。结果:喉鳞状细胞癌组织中PDCD4蛋白阳性表达率低于癌旁正常喉黏膜组织(P<0.01),喉鳞状细胞癌组织中PDCD4蛋白阳性表达和喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期无关,与病理分级、淋巴结转移有关(P<0.05);喉鳞状细胞癌组织细胞PI明显高于癌旁正常喉黏膜组织(P<0.01),细胞PI与喉鳞状细胞癌临床分型(肿瘤部位)、病理分级、淋巴结转移无关,与TNM分期有关(P<0.05);喉鳞状细胞癌组织细胞AI明显高于癌旁正常喉黏膜组织(P<0.01),细胞AI与喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期、淋巴结转移无关,与病理分级有关(P<0.01);喉鳞状细胞癌PDCD4阳性表达的细胞PI低于阴性组(P<0.05),细胞AI高于阴性组(P<0.05)。结论:PDCD4在喉鳞状细胞癌中低表达,可能与喉鳞状细胞癌细胞的增殖和凋亡均有一定的关联。     

Videolaryngostroboscopy and voice evaluation in patients with rheumatoid arthritis

Arthritis may affect the larynx and produce symptoms such as hoarseness and vocal fatigue.ObjectiveThis paper aimed to evaluate the laryngeal manifestations of rheumatoid arthritis.MethodsThis is prospective study assessed 27 patients with rheumatoid arthritis with the aid of videolaryngostroboscopy, auditory-perceptual analysis of the speech using the GIRBAS scale, acoustic analysis and the Voice Handicap Index questionnaire.ResultsNineteen patients had laryngeal complaints, the main ones being intermittent dysphonia and sensation of a foreign body in the throat. The most frequent laryngoscopical finding was overlapping arytenoids. Three patients had low pitch, nine patients had mild dysphonia and roughness. Median acoustic measures were: F0, 198.39 Hz; Jitter, 0.815; Shimmer, 4.915; and NHR, 0.144. Regarding the Voice Handicap Index, the median score was zero in all domains. There was a statistically significant correlation between voice complaints and the domains of this index. Functional classes were significantly correlated to: overlapping arytenoids (p = 0.001), PPQ (p = 0.0257), Shimmer (p = 0.0295), APQ (p = 0.0195), and the VHI physical (p = 0.0227) and total domains (p = 0.0425).ConclusionLaryngeal complaints were reported by 70.4% of the patients and laryngoscopical alterations were observed in 48% of the subjects. Voice acoustic evaluation and self-perception were altered.