Reduced E-cadherin expression is associated with lymph node metastases in laryngeal squamous cell carcinoma

Objective

To investigate the expression of E-cadherin and its relationship with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC).

Methods

Sixty-four patients who had previously undergone complete resection of tumor for LSCC were studied retrospectively. The level of E-cadherin expression in tumor tissues and paired nontumor tissues were determined by immunohistochemistry.

Results

The expression of E-cadherin in tumor tissues was significantly lower than nontumor tissues (P < 0.001). Reduced E-cadherin expression was significantly correlated with lymph node metastases (P < 0.001). Kaplan–Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival rate (log-rank P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P = 0.001) and tumor stage (P = 0.013) were statistically significant, independent predictor of prognosis.

Conclusion

Expression of E-cadherin is an independent predictor of lymph node metastases in LSCC. However, it does not appear to be a better prognostic predictor than other established markers in LSCC.     

Wyniki leczenia operacyjnego raka krtani w różnych typach laryngektomii częściowej na podstawie materiału własnego

The aim

of the study was to evaluate the oncological results of laryngeal cancer treatment performed in the Laryngology University Ward in Zabrze in the years 1990–2000, depending on the type of partial surgery applied.

Materials and methods

Retrospective clinical material includes 209 patients in whom surgery was a primary treatment method. No distant metastases (M1) or another malignant cancer were found. In all 209 patients the squamous cell carcinoma of various degree of malignancy (G₁–G₃) was found. The most common operation in the analyzed group was a chordectomy – 83 surgeries (40%), next, vertical partial laryngectomies – 38 (18%), horizontal glottis surgeries – 28 (13%). In 79 patients (38%) partial laryngectomy was complemented with a nodal operation.The median of the observation period was 9 years. Local recurrence, nodal recurrence and distant metastasis are rated as treatment failure. Treatment effectiveness was evaluated with relation to overall survival, disease-free survival, cause specific survival and local control. All the above-mentioned parameters were analyzed with the updated percentages method. The level of statistical significance was assumed to be p ≤ 0.05.

Results

The best oncological results were observed after vertical operations. In the vertical operations group the most favourable oncological results were noted after chordectomy. 83% overall survivals, 82% disease-free survivals, 93% cause specific survivals and 96% local controls in the 5-year observation. On the other hand, the least favourable treatment results were observed after ¾ subtotal partial operation, after horizontal supraglottic operation and after reconstruction operation with CHP. Statistically significant differences in treatment results between the groups of patients after various types of partial operations were found in relation to local controls and disease-free survivals.     

Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx

Objective

To present the first reported case of a simultaneous squamous cell carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and the 9-month follow-up results.

Study design

Case study.

Methods

Review of diagnostic studies, the operative technique, and the patient's chart for the 9-month period after treatment.

Results

A case with double laryngeal tumors with simultaneous evolution but different histological patterns is described. The squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the anterior commissure. A partial laryngectomy was performed, and the patient has been free of disease for 9 months.

Conclusions

Multiple laryngeal tumors are exceedingly rare. To our knowledge, no previous reports of a simultaneous squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported. Both tumors were not invasive in this case, so conservation surgery was feasible.     

Results after supracricoid horizontal partial laryngectomy

Objectives

This study analyzed oncological and functional results of supracricoid horizontal partial laryngectomy.

Methods

A retrospective study was conducted involving 20 patients with squamous cell carcinoma (SCC) of the larynx who underwent SCPL between 1996 and 2005 in Faculty of Medical Sciences of Santa Casa Hospital of Sao Paulo, Brazil. There were 18 male and 2 female patients with ages ranging from 39 to 74 years (median = 58 years), of whom 19 were smokers and 14 alcoholics. The tumors were present in the glottis in 16 cases and supraglottis in 4; 5 were stage I or II and 15 were stage III or IV. We analyzed treatment given when rehabilitation was unsuccessful, oncological results of SCPL, including local and regional recurrences, time to recurrence and treatment given, distal metastases, global survival, survival free of disease, and appearance of second primary tumors. We also calculated the index of functional preservation of the larynx.

Results

Rehabilitation of swallowing capabilities and speech was achieved in 18 patients. Removal of the tracheostomy varied between 1 and 9 months. Rehabilitation was unsuccessful in two patients. Three patients required a total laryngectomy, two for unsuccessful rehabilitation and one for recurrence. The preservation of a functional larynx was 85%, with 10% of patients requiring a total laryngectomy after failed rehabilitation.

Conclusions

Supracricoid horizontal partial laryngectomy is an efficient surgical oncology technique that yields good functional results for the treatment of laryngeal cancer.     

Voice-related quality of life in patients after total and partial laryngectomy

Objective

To assess the voice-related quality of life (V-RQOL) in patients after total and partial laryngectomy.

Materials and methods

96 patients treated for laryngeal cancer were enrolled in the study. The cohort of patients was divided into three groups depending on the surgical procedure carried out: total laryngectomy (TL), supracricoid partial laryngectomy (SCL) and/or horizontal glottectomy (HG). The maximum phonation time (MPT) and syllable diadochokinesis, were used for the aerodynamic assessment; Yanagihara score was used for acoustic analysis of the sustained /a/ and the GRBAS scale was used for perceptual assessment. Each of the patients completed the VHI. The Kruskal–Wallis and Mann–Whitney tests were used to analyse the mean difference among the three groups of patients.

Results

A comparison with the values found between groups noted that the TL group showed significantly higher scores of G, R and Yanagihara score, while the HG group showed a significantly higher score of B. No differences were found in the aerodynamic and acoustic measures among the 3 groups. The mean ± standard deviations of VHI total score were 35.3 ± 24.5 for TL group, 30.1 ± 21.6 for SCL group, 35.8 ± 9.6 for HG group. No significant difference was found across the three groups.

Conclusions

V-RQOL seems to be similar in patients who underwent significantly different surgical procedures even if the voice characteristics were different. These findings need to be considered in patient's counselling together with other data on general quality of life after total and partial laryngectomy.     

Expression of claudin-3 in the esophagus and larynx of rat reflux model

Objective

The aim of this study was to investigate the association between laryngeal expression of claudin-3 and laryngopharyngeal reflux (LPR) in a rat reflux model.

Methods

Eight Wistar rats were divided into two groups. Four rats underwent total esophageal myectomy to induce reflux, and the remainder underwent a sham operation as a control. All animals were sacrificed 12 weeks after surgery to perform tissue histology and Western blot analysis.

Results

Lymphocyte infiltration increased significantly in the study group in both esophageal and laryngeal samples (P = 0.001, 0.002, respectively). Both esophageal and laryngeal expressions of claudin-3 were significantly lower in the study group when compared with that in the control group (P = 0.045, 0.037, respectively).

Conclusion

The results of this study suggest that a decrease in claudin-3 could be a sensitive indicator of reflux laryngitis in rats.     

Hypopharyngeal mucosal flap reconstruction in endoscopic supraglottic laryngectomy

Purpose

Preservation of voice, swallowing and airway is mandatory in early to moderately advanced supraglottic cancers. Here, we propose an endoscopic laryngoplasty to improve swallowing recovery in patients treated by extended CO₂ laser supraglottic laryngectomy.

Methods

We describe a new mucosal flap reconstruction technique in a cohort of seven laryngeal cancer patients with posterior extension, treated by CO₂ laser resection. Clinical endoscopic and videofluoroscopy postoperative exams were performed, and swallow function was tested by the MD Anderson Dysphagia Inventory (MDADI) questionnaire.

Results

No early complications were observed. Absence of aspiration after two days in all cases was confirmed, and MDADI mean value result was 98.

Conclusions

We suggest the harvest of a hypopharyngeal mucosal flap in all patients who require a laryngeal supraglottic posterior resection, with or without arytenoidectomy.     

High Gpx1 expression predicts poor survival in laryngeal squamous cell carcinoma

Objective

Several studies have demonstrated that abnormal glutathione peroxidases 1 (Gpx1) expression can influence the biological behavior of malignant cells. However, the roles of Gpx1 in laryngeal squamous cell carcinoma (LSCC) remain unknown. The purpose of this study is to analyze the Gpx1 expression and prognostic significance in LSCC patients.

Inhibiting XIAP expression by RNAi to inhibit proliferation and enhance radiosensitivity in laryngeal cancer cell line

Objectives

X-linked inhibitor of apoptosis protein (XIAP) is a novel member of the inhibitors of apoptosis (IAPs) family. The overexpression of XIAP is asscociated with radioresistance of human malignancies. The purpose of the present study was to investigate the effect of shRNA-targeted XIAP on the proliferation, apoptosis and radiosensitivity of human laryngeal carcinoma cells (Hep-2).

Methods

A siRNA expression vector (pSilencer4.1-XIAPshRNA) was constructed and stably transfected into human laryngeal carcinoma cells (Hep-2). The downregulation of XIAP expression was evaluated by RT-PCR and Western blot analyses. Then, we investigated the effect of XIAP-shRNA on the proliferation, cell cycle changes and apoptosis in vitro of Hep-2 cells. Finally, the radiosensitivity of Hep-2 cells was investigated by clonogenic cell survival assay.

Results

We established stably transfected cell line (Hep-2/XIAPshRNA) in which the expression of XIAP gene was downregulated. The cell viability of Hep-2/XIAP-RNA cells was obviously decreased compared with that of untransfected Hep-2 cells. Morever, XIAP-shRNA induced cell arrest in the G₀/G₁ phase of cell cycle by flow cytometry analysis. Results of TUNEL assay indicated that Hep-2 cells stably transfected pSilencer4.1-XIAP-shRNA showed obvious apoptosis characters. Furthermore, the downregulation of XIAP expression could lead to significant radiosensitivity enhancement in laryngeal carcinoma cells.

Conclusions

RNAi-mediated downregulation of XIAP expression can inhibit proliferation, induce apoptosis and diminish the radioresistance of laryngeal carcinoma cells, so combined therapy with XIAP inhibition and radiation may be a potential strategy for the treatment of laryngeal carcinoma.     

Transoral laser microsurgery in previously irradiated patients with laryngeal cancer

Purpose

Early laryngeal cancer is successfully managed with transoral laser microsurgery. Previously radiated patients may experience more post-operative complications. We investigate disease-free survival and secondarily prolonged pain and chondronecrosis.

Materials and methods

Retrospective review of 52 patients undergoing transoral laser microsurgery after previous radiation.

Results

Mean disease-free survival was 36.7 months. Overall disease-free survival was 57.6% at 3-year and 48.4% at 5-year follow-up, with no significant difference between surgery within as opposed to after 60 months of radiation or within as opposed to after 12 months of radiation. Thirteen patients, all with surgery within 60 months of radiation, experienced prolonged pain. Twelve experienced chondronecrosis, all within 12 months of surgery.

Conclusion

Transoral laser microsurgery for early laryngeal cancer is an adequate therapeutic option in patients with history of radiation with comparable disease-free survival to other reports. Patients undergoing transoral laser microsurgery within 60 months of radiation treatment are more likely to experience prolonged pain.     

Laryngeal cleft: Evaluation and management

Objectives

Review the latest diagnostic and treatment modalities for laryngeal and laryngotracheoesophageal clefts as they can be a major cause of respiratory and feeding morbidity in the infant and pediatric population.

Methods

Literature review of published reports.

Results

The presentation of laryngeal cleft usually involves respiratory symptoms, such as stridor, chronic cough, aspiration, and recurrent respiratory infections. Clefts of the larynx and trachea/esophagus can occur in isolation, as part of a syndrome (Opitz-Frias, VATER/VACTERL, Pallister Hall, CHARGE), or with other associated malformations (gastrointestinal, genitourinary, cardiac, craniofacial). This publication reviews the presenting signs/symptoms, diagnostic options, prognosis, and treatment considerations based on over a decade of experience of the senior author with laryngeal clefts.

Conclusions

Type I laryngeal clefts can be managed medically or surgically depending on the degree of morbidity. Types II, III, and IV require endoscopic or open surgery to avoid chronic respiratory and feeding complications.     

An extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer

Objectives

To present an extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer.

Materials and methods

A 74-year-old male who noted a mass on the lower anterior neck and consulted our department immediately. The mass rapidly grew to 6 cm from 2 cm in diameter within 2 months after the initial presentation.

Results

Fiberoptic laryngoscopy was unremarkable. Surgical excision of the lesion showed well differentiated squamous cell carcinoma with invasion into the surrounding tissues. Postoperative radiotherapy was added. During follow-up after those treatments, thickening of the right vocal cord was observed, which gradually became more apparent. Total laryngectomy was performed 13 months after the initial operation.

Conclusion

Delphian node metastasis is included in the differential diagnosis in a case of rapidly increasing mass in the anterior neck.     

Expression of Epidermal Growth Factor Receptor variant III in laryngeal carcinoma tissues

Objectives

Epidermal Growth Factor Receptor variant III (EGFRvIII) has been believed to be an attractive tumor-specific candidate for molecular targeting therapy. However, there is little literature dealing with this variant of EGFR expressed in laryngeal carcinomas. In the present study, we try to evaluate the expression of EGFRvIII, as well as EGFR, in laryngeal carcinoma tissues and its correlation with clinicopathological features.

Methods

Real-time polymerase chain reaction (real-time PCR) with TaqMan probes was applied to detect the expression for EGFR and EGFRvIII mRNA in the 39 pairs of samples of laryngeal carcinoma tissues and microscopically normal laryngeal mucosal tissues adjacent to the tumor. 2^−ΔΔCT method was used to obtain the relative quantity of target mRNA expression. The correlation between EGFRvIII expression and its clinicopathological features was analyzed by Pearson's chi-squared test.

Results

Among the 39 pairs of samples of laryngeal carcinoma tissues and microscopically normal laryngeal mucosal tissues adjacent to the tumor, the level of EGFR mRNA of the former (0.030 ± 0.076) was higher than that of the latter (0.011 ± 0.046) (P < 0.01). EGFRvIII mRNA was detected only in six samples of laryngeal carcinoma tissues. While, as control, in 39 samples of microscopically normal laryngeal mucosal tissues, EGFRvIII mRNA was hardly detected. As analyzing the correlation between expression of EGFRvIII and EGFR, we found the positive rate of EGFRvIII expression was higher in samples with relative EGFR mRNA value ≥0.025 than those of EGFR mRNA <0.025. The difference between them was statistically significant (P < 0.05).

Conclusions

Expression of EGFRvIII in laryngeal carcinoma was confirmed in this study. It is tumor-specific and tends to be more frequent in EGFR-over expressing tumor tissues and poorly differentiated ones, which may in part contribute to the malignant phenotype.     

Stagewise treatment of anterior commissure laryngeal web and recurrent laryngeal papillomatosis under endoscope

Objective

To evaluate the stagewise treatment of anterior commissure laryngeal web caused by recurrent laryngeal papillomatosis.

Methods

One patient with anterior commissure laryngeal web caused by recurrent laryngeal papillomatosis underwent laryngomicrosurgery three times. At the same time of using CO₂ laser to remove papilloma, we performed vocal cord mucosal flap repair and suture.

Results

After 1 year following up, laryngeal papilloma did not recur and the voice quality of the patient significantly improved with no wheezing sound.

Conclusion

This method can resolve the problem of recurrence and adhesion in laryngeal papilloma.     

Lateral cervical approach for supracricoid partial laryngectomy

Introduction

The supracricoid partial laryngectomy has been described for the treatment of T3 laryngeal glottic and supraglottic tumors as well as upfront and salvage surgery. Good oncological and functional outcomes are expected, while the post-operative rehabilitation can be quite difficult for the patient. Early and late complications can occur especially in salvage surgery. Neck dissection according to the T stage is often associated with the resection of the primary tumor.

Long-term results of open cordectomy for the treatment of T1a glottic laryngeal carcinoma

Objective

To assess the long-term results and prognostic factors in patients who have undergone open cordectomy (OC) for the treatment of T_1a glottic laryngeal carcinoma.

Methods

One hundred four epidermoid cancer patients operated from January 1989 through December 1999 were included in the study. Clinical parameters, postoperative complications, and postoperative stay were retrospectively evaluated in all cases.

Results

Mean survival for the patients included in the study was 61.5 ± 24.8 months after the date of operation (range: 11–121 months). Ninety-four patients did not have recurrent tumor (90.4%). Local, regional and distant recurrence were linked with a statistical negative impact on survival rates (p < 0.05). Only sero-hematoma was significantly related to local recurrence (p < 0.05), whereas the remainder complications did not. None of the complications was associated with neck recurrence or distant metastasis (p > 0.05).

Conclusions

Open cordectomy is nowadays a valid technique for the surgical treatment of T_1a glottic laryngeal carcinoma. Its results are comparable with those of other more recent techniques.     

Buccal fat augmentation for insufficient neoglottal closure after supracricoid laryngectomy with cricohyoidoepiglottopexy

Objective

Supracricoid laryngectomy with Cricohyoidoepiglottopexy (SCL-CHEP) is a functional organ preservation surgery for laryngeal cancers. Post-operative laryngeal function is generally promising. Some patients, however, cannot attain satisfactory functional results because of an excessively wide neoglottis resulting in an insufficient neoglottal closure. Autologous buccal fat augmentation was conducted to correct the insufficiency.

Patients and Methods

Two patients underwent intervention. Under general anesthesia, autologous fat was harvested from the buccal fat pad. Fat tissue was injected into the widest plane of the neoglottis under direct laryngoscopy; a navigation system was incorporated to identify the responsible site. Acoustic, aerodynamic, and perceptual analyses along with videofluoroscopic swallowing study and screening questionnaires were used for functional evaluation.

Results

A total of 0.8 ml (Case 1) and 0.7 ml (Case 2) of fat tissues were injected into the submucosal space of the responsible sites. Both patients experienced functional improvement subjectively after augmentation; psychological parameters for voice and swallowing also improved.

Conclusions

Buccal fat augmentation to correct insufficient neoglottal closure after SCL-CHEP was technically feasible. A navigation system was helpful for confirmation. Fat absorption occurred and one third of the volume remained at 3 and 6 months. Although, vocal measurements remained unchanged, psychological parameters for voice and swallowing improved.     

Use of concurrent chemoradiation in advanced staged (T4) laryngeal cancer

Hypothesis

Patients with advanced laryngeal cancer sometimes desire organ preservation protocols even if it portends a worse outcome.