Glottic Tumors Research Articles

Cancer of the Larynx- Management Challenges in Calabar, South-South Nigeria.

Aims: To review the management challenges and outcome of advanced carcinoma of the larynx associated with patient treatment preference regardless of available or clinically appropriate treatment modality. Materials and methods: This was a retrospective review of the records of patients with laryngeal cancer managed in the Otorhinolaryngology department of the University of Calabar Teaching Hospital, Calabar South eastern Nigeria. The period under review was April 2001 to march 2011. The age, sex, presentation, history cigarette smoking and alcohol consumption, histopathological diagnosis, patient treatment preference and outcome of management, were analysed. Results: There were 10 patients, all males in the age range 42 to 75 years. Hoarseness was the initial symptom in all the patients (100%) with stridor and difficulty in breathing in 8(80%) at presentation. There was history of recent or past cigarette smoking in all but 2 (20%) of the patients. Tumour was transglottic in 7 (70%) patients, glottic in 2 (20%) and supraglottic in 1 (10%). Emergency tracheostomy was done in 8 (80%) cases as the first line of treatment to relieve upper airway obstruction. The histological diagnosis was exclusively squamous cell carcinoma of variable degrees of differentiation in 9 (90%) cases and carcinoma in situ in a case (10%) patient. Clinical staying was T3 No in 8(80%) of cancer. Nodal staging was not confirmed by CT or MRI scans. There was biased to any form of laryngeal surgery as treatment option because of societal believes and ignorance. Chemoradiation therapy without surgery preferred by all the patients regardless of advanced stage of disease. There was high morbidity including disease recurrence within 1 year in 7(70%) patients and dependence on tracheotomy in 8(80%), feeding gastrostomy, intractable pain and pharyngocutaneus fistula. Voice optimisation was achieved only in the 2 patient with early glottic tumours. Mortality within 1 year was recorded in 5 patients despite Chemoradiation Therapy (CRT). Mortality was attributable to liquid morphine overdose/toxicity in 1 patient. Prognosis was abysmally poor.Conclusion: Treatment of Ca larynx in Calabar South eastern Nigeria is a management challenge with considerable morbidity and mortality. Cure rate and prognosis are very poor because of late presentation and patient’s preference for inappropriate treatment modality in advanced disease. Refusal of laryngeal surgery as treatment option even when conservative non-surgical options have failed was because of Beliefs and ignorance. There is need for public enlightenment on the possibility of high cure rates and voice preservation in early laryngeal cancer. Cost of oncology care should be subsidized by government while an oncology centre should be established in each of the six geopolitical zones in Nigeria.

Cirugía transoral LASER CO 2 en tumores avanzados de faringe y laringe

Introduction and objectives There are several types of treatment for advanced squamous cell carcinomas of the pharynx and larynx. However, both open surgery and chemoradiation protocols have failed to improve control and survival. There is a tendency toward conservative treatment without worsening oncological outcomes. The objective of this study was to describe the effectiveness of organ-preserving CO 2 laser microsurgery for treating advanced carcinomas of the larynx and pharynx. Material and method A retrospective review of 63 patients undergoing CO 2 laser microsurgery for the treatment of squamous cell carcinomas of the pharynx and larynx in advanced stages (stages III and IV) was performed. Tumour distribution was 14 patients with a tumour at the base of the tongue, 16 with a pyriform sinus tumour, 29 with a supraglottic tumour and 4 with a glottic tumour. Mean follow-up was 51 months. Results Thirty-five percent of patients (23) had recurrences. The recurrence rate was 28% for base of tongue tumours, 50% for hypopharyngeal tumours, 27% for supraglottic tumours and 75% for glottic tumours. The 5-year disease-specific survival rate was 73.3% for all locations, with a range from 90% for supraglottic tumours up to 50% for glottic tumours. Thirty-four percent of patients had some type of complication after surgery. The most frequent complication was local bleeding (17%). Conclusion Transoral CO 2 laser microsurgery is an alternative for the treatment of carcinomas of the pharynx and larynx in advanced stages. Its oncological results are equivalent to other treatment modalities and its morbidity is lower.

Endoscopic Treatment with Radiofrequency in Larynx Cancer

Carlos S Ruggeri Hospital Italiano de Buenos Aires carlos.ruggeri@hospitalitaliano.org.ar (0054) 11-4959-0200 (8368) Objectives The aim of this study is to demonstrate that microsurgical treatment with uncontrolled radiofrequency in glottic and supraglottic tumors staged as Tis, T1, T2 and T3 have analogous results to those described in the literature for microsurgical treatment with CO2 laser in similar staging laryngeal cancer. Methods and Materials Descriptive, prospective and retrospective study of patients with glottic and supraglottic malignant tumors undergoing microsurgery of the larynx with Rfq between March 2004 and December 2009. Results Fourty-four patients were treated, 38 males and 6 females. 39 were glottic and 5 supraglottic tumors. The local control rate of the disease with an average follow up of 2.3 years was 90.9% (40/44). Total laryngectomy and endoscopic cordectomy were performed in two different patients as rescue procedure.The final local control rate was 93.18%. Conclusions Microsurgical resection of malignant laryngeal tumors with uncontrolled radiofrequency is an effective treatment, with similar local control rates, complications and morbility as the reported with CO2 laser. Endoscopic Treatment with Radiofrequency in Larynx Cancer

Transoral laser microsurgery for T3 laryngeal tumors: Prognostic factors

The objective of this study was to evaluate the outcomes of transoral laser microsurgery (TLM) in T3 laryngeal carcinomas and to identify prognostic factors for survival and laryngeal preservation. This study aimed to provide a retrospective analysis of 147 consecutive patients, evaluating their overall survival, disease-specific survival, laryngectomy-free survival, and function preservation rate. Five-year overall, disease-specific, and laryngectomy-free survivals were 53.1%, 70.2%, and 62.3%, respectively. Disease-specific survival differed between glottic and supraglottic tumors (86.3% vs 61.8%; p = .015). Function preservation was 65.5% in supraglottic and 49.1% in glottic tumors (p = .002). Disease-specific survival was not related to pre-epiglottic involvement, cord fixation, or focal cartilage infiltration (p > .05). Vocal cord fixation and cartilage infiltration were independent negative prognostic factors for organ preservation (odds ratio [OR] = 0.184; 95% confidence interval [CI] = 0.082-0.411; p = .000 and OR = 0.331; 95% CI = 0.139-0.789; p = .013, respectively). Our conclusion is that TLM is a good alternative in a large number of T3 laryngeal tumors, with adequate survival and organ preservation rates above 60%.

Structures Constituting the Sound Source After the Treatment of Early Glottic Cancer

We indicate the exclusive radiation therapy as initial approach for T1a glottic tumors, and the frontolateral laryngectomy for the tumors staged as T1b and selected T2 glottic tumors. The videolaryngostroboscopy is a useful tool to analyze the laryngeal structural changes and compensatory motion after the therapeutic approach. To evaluate the endolaryngeal structures of patients who participate in the vibratory sound source after the early glottic cancer treatment through the videolaryngostroboscopy. It was a retrospective transversal study in which 20 patients who underwent exclusive radiation therapy and 25 patients who underwent frontolateral laryngectomy were analyzed by means of videolaryngostroboscopy. The radiation doses ranged from 5000 to 7020 cGy in the radiation therapy group. The mucosal wave and the vibratory source components were evaluated. All of the irradiated patients presented vibratory behavior, and hyperfunction was occasionally observed in four cases. The mucosal wave source was glottic in 18 cases and mixed in two cases. In the laryngectomy group, 10 supraglottic sources, 10 glottic sources, and five mixed sources were identified. Among the 10 cases of supraglottic source, eight patients presented global constriction and two patients presented medial constriction. Among the five cases of mixed source, two patients presented global constriction, one patient presented medial constriction, and one patient presented anteroposterior constriction. Regarding the number of anatomical structures presenting vibratory pattern, five patients had two structures, four patients had three structures, and one patient had four structures. Patients who underwent radiation therapy recruit less supraglottic structures as vibratory source than the patients undergoing vertical laryngectomy.

Surviving Hypopharynx–Larynx Carcinoma in the Era of IMRT

Outcome in locoregionally advanced laryngeal carcinoma and hypopharyngeal carcinoma after conventional radiation techniques is known for modest disease control and considerable late toxicity. Considering the lack of standardization in prescription dose for intensity-modulated radiotherapy (IMRT), we aimed to compare the results after our methods of simultaneously integrated boost IMRT with published results. Between March 2002 and December 2008, 65 hypopharyngeal, 31 supraglottic, and 27 locoregionally advanced glottic tumor patients underwent definitive IMRT (with simultaneous chemotherapy in 86%). Of these, 64% presented with locoregionally advanced disease. Mean follow-up was 26 months (range, 3-83 months), with a median of 21 months. Treatment (2.0-2.2 Gy per fraction, 66-72.6 Gy) followed a prospectively defined protocol. If the boost volume included more than half of the larynx or a substantial part of the pharynx, dose was limited to 2.0 Gy per fraction. The 2-year local, nodal, and locoregional control (LRC) rates for the entire cohort were 82%, 90%, and 77%, respectively; the disease-free and overall survival rates were 75% and 83%, respectively. The ultimate 2-year LRC rate, including salvage surgery, was 86%. Laryngectomy was required in 2 LRC patients needing tracheostoma already before; 2 further LRC patients needed tracheostomy before IMRT and remained tracheostoma dependent, and 3 patients remained feeding tube dependent after IMRT. Salvage laryngectomy was successful in 8 of 11. Of all 123 patients, 91 patients (74%) are locoregionally controlled and live with a functional laryngopharynx. Simultaneously integrated boost IMRT with limited acceptance of dose inhomogeneity resulted in very satisfactory disease control despite a slight left shift of planning target volume curves on the dose-volume histogram. Considering the treatment tolerance, a careful increase in dose in our patients seems possible. Dose-volume comparisons remain difficult because no international standards have been defined for contouring and volume-related dose distribution.

Abstract A126: Analysis of excision repair cross complementing group 1 (ERCC1) expression in squamous cell carcinoma of the head and neck (SCCHN)

Abstract Introduction: ERCC1 is a key enzyme in the nucleotide excision repair pathway and increased expression of ERCC1 is associated with cisplatin resistance in some cancers. Given the widespread use of platinum therapy for the treatment of SCCHN, we characterized the range of ERCC1 expression in SCCHN specimens using an immunofluorescence-based assay (automated quantitative analysis-tissue microarray [AQUA-TMA]). There is currently inadequate data regarding the range of ERCC1 expression in SCCHN, and how ERCC1 levels correlates with treatment outcomes, ERCC1 has been studied in SCCHN by standard immunohistochemistry, however, this method is limited by variability of techniques and subjectivity of interpretation, Therefore, there is a need for a highly quantitative technique which can be accomplished on formalin fixed paraffin embedded tissue and small samples, Our goal is to develop a reproducible assay that can eventually be incorporated into standard patient care practice. Methods: Tissue microarrays containing head and neck squamous cell carcinoma samples obtained from patients treated at Fox Chase Cancer Center from 1999–2006 were constructed. Slides were stained by a modified indirect immunofluorescence method. Sections were incubated with ERCC1 antibody (8F1, Lab Vision) and wide-spectrum screening rabbit cytokeratin antibody (Dako Z0622). Prolong Gold mounting medium (P36931; Molecular Probes) containing 4,6-Diamidino-2-phenylindole (DAPI) was used to define tissue nuclei. A binary image (tumor mask) was created from the cytokeratin image of each histospot. ERCC1 levels were measured using fluorescent immunohistochemistry on the HistoRx PM-2000 image analysis platform and the data analyzed using AQUA algorithms. The in situ biomarker profiling system generated quantitative measurements of patient protein levels based on AQUA scores derived from fluorescent output of labeled markers. Both nuclear and non-nuclear (i.e., non-membrane/cytoplasmic) ERCC1 expression was measured Results: 41 SCCHN specimens (24 oral cavity, 7 oropharynx, 5 glottic tumors, 3 unknown primary, 2 other) were analyzed. There were 25 males and 16 females and age at diagnosis ranged from 25 to 80 years (mean 64). The majority of patients were treated primarily by surgery. The range of AQUA scores was 33.66 to 1696.39 (mean 501.78, stnd deviation 284). The 25th percentile was 337.35, and the 75th percentile was 639.37. ERCC1 was predominantly nuclear (i.e., non-membrane/cytoplasmic) in the SCCHN tissue samples. Conclusions: 1) It is feasible to determine a quantitative value of ERCC1 expression with AQUA. 2) There is a wide range of ERCC1 expression in SCCHN. 3) ERCC1 is predominantly localized to the nuclear compartment. 4) Ongoing work is being done to correlate ERCC1 levels with clinical features, sensitivity to platinum therapy, and survival. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A126.

Transoral CO2 laser treatment for Tis–T3 glottic cancer: The University of Brescia experience on 595 patients

Transoral CO(2) laser surgery has been accepted as a valuable therapeutic option for glottic cancer. This was a retrospective analysis of 595 patients. Five-year overall and disease-specific survivals, local control with laser, locoregional, regional control, and organ preservation rates were calculated. The impact of different variables was calculated by univariate analysis. Overall, disease-specific and disease-free survivals, local control with laser, locoregional, regional control, and organ preservation rates were 87.5%, 99%, 81.3%, 92.7%, 98.9%, 98.2%, and 97.1%, respectively. Univariate analysis showed a significant impact of pT category on local control with laser, organ preservation, locoregional and regional control, of endoscopic re-treatment for positive deep surgical margins on local control with laser and organ preservation, and recurrence after endoscopic re-treatment on local control with laser and organ preservation. This series confirms the good oncologic outcomes of endoscopic laser surgery for T(is), T(1), and selected T(2) and T(3) glottic tumors.

Fatores prognósticos e impacto da comorbidade na laringectomia fronto-lateral

To evaluate the survival rates, comorbidity impact, complications, and treatment failure facts. 38 patients clinically staged as T1b / T2N0M0 glottic tumors were analyzed. They underwent frontolateral laryngectomy with reconstruction, from January, 1995 to December, 2006. The oncological outcome, comorbidity (through the Adult Comorbidity Evaluation -27 ACE-27 scale) and complications were studied and correlated to the demographic data and tumor characteristics. Eight patients presented local recurrence being surgically salvaged. Complications were not observed in 33 patients. There was no significant difference on the global and free of disease 5-year survival regarding the diverse comorbidity categories. Only the pathological margins spread of the tumor presented significant difference on the global (p=0.0033) and free of disease survival (p<0.0001). The 5-year global survival was 67.6% whereas the free of disease survival was 73.7%; the comorbidity did not represent independent prognostic factor; the postoperative complications rate was 13.2%; and only the pathological margin spread showed significant difference on the global and free of disease survival rates.

The epidemiology of laryngeal cancer in a country on the esophageal cancer belt

Laryngeal cancer is one of the most common malignant neoplasms of the head and neck and occurs predominantly in males. Squamous cell carcinomas arising in the glottic region are the most common of all laryngeal cancers and more prevalent than the supraglottic ones. But this pattern is reverse in some countries. This study was done to investigate the epidemiologic aspect of this subject in Iran. Cross-sectional study During a ten-year period from 1997 to 2007, all patients referred to two tertiary referral hospitals with a diagnosis of laryngeal cancer were enrolled in this study. Laryngeal cancer was diagnosed in a total of 453 patients and confirmed histologically. The average patient age was 59.92 years. Men outnumbered women (9.5:1). Four hundred patients (88.5%) were tobacco smokers. The primary location of the tumor was supraglottic in 221 (49%) cases, followed by glottic in 163 (36.2%), transglottic (the tumor involved all regions of the larynx and the origin was unspecified) in 60 (13.3%), and subglottic in 7 (1.6%). In our series, although we excluded transglottic tumors, the supraglottic tumor was dominant and the ratio of supraglottic to glottic tumors was 1.36. This is compatible with results from countries with a reverse ratio.

Functional vocal results after CO2 laser endoscopic surgery for glottic tumours

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Myoepithelioma of the larynx: a case report

Myoepithelioma of the larynx is a very rare tumor with nonspecific local symptoms. We present the second known case, focusing on the peculiarities of the differential diagnosis for this type of tumor that are crucial for the right histologic diagnosis and furthermore for the therapeutic outcome.We report a 37-year-old male presenting with hoarseness and dyspnea. The indirect laryngoscopy revealed a gross glottic tumor from the right vocal cord who occupied the greater part of the glottis. No apparent cartilage invasion was shown in the CT. He came to us with a previous direct laryngoscopy derived biopsy describing a chondroma. A modified vertical partial laryngectomy, under temporary tracheostomy, with muscle reconstruction for the deficit of the right vocal cord was applied for the removal of the tumor. The final histopathologic diagnosis was myoepithelioma (spindle cell type) of the larynx. A long term follow-up in our case showed no recurrence and a good functional result.The larynx is a very rare localization for this type of tumour. The benign character of the disease in conjunction with its slow progression could delay its detection and diagnosis, leading to a more destructive surgery. A detailed pathology examination is prerequisite for avoidance of misleading diagnosis.

Isolated intracranial metastasis from an early glottic cancer: how rare a presentation?

The incidence of distant metastasis with laryngeal tumors varies from 1-4% [1]. The lungs are the most frequent site, followed by bone and liver. Intracranial metastases are rarely clinically diagnosed in head neck cancer patients and if present are mainly located in the cerebrum and cerebellum. Early stage glottic squamous carcinoma with subsequent distant metastasis is rare [2]. We report a patient with T1N0 glottic tumor who underwent a curative radiotherapy and on 3 months follow up presented with isolated intracranial metastasis.

Pathological examination of cordectomy specimens: Analysis of negative resection

Objective Occasionally, after performing a cordectomy to treat a T1 glottic tumor, the pathologist does not detect carcinomatous cells in the surgical specimen. This study determined how often this happens and analyzed these cases to identify related variables. Methods Forty-six patients were studied. Data on patient age and gender, tumor T stage and macroscopic surface extension, device used (laser vs. microelectrode dissection (ME)), and presence/absence of a negative cordectomy were compiled. We performed excisional biopsies as a diagnostic procedure. Results Tumor stage was carcinoma in situ (Cis; 11 cases), T1a (28 cases), or T1b (7 cases). Nineteen tumors were limited, and 27 were extensive. Twenty-one patients underwent laser surgery, and 25 had ME. There were 12, 21, 4, and 9 types II to V cordectomies, respectively. The pathologist reported 15 negative cordectomies (32.6%). Only tumor extension was significantly associated with a negative cordectomy ( p = 0.047). Conclusion In 32.6% of our cases, the excisional biopsy was diagnostic and therapeutic. This percentage rose to 52.6% in the cases of limited tumors. We recommend performing an excisional biopsy and limited resection of the surgical bed with ME or laser surgery. A pathologist can examine the margins to determine whether the resection should be extended. When choosing radiotherapy, it is better to first perform an incisional biopsy to obtain a diagnosis of carcinoma.

Squamous cell cancer of the head and neck (SCCHN) with distant metastasis at presentation

6053 Background: SCCHN is confined to the head and neck region in the majority of patients at presentation. Unfortunately, some patients have distant metastasis at presentation and this has a significant effect on treatment and prognosis. Current literature reports a rate of distant metastatic disease at presentation between 1.5% and 16.8%. This is based on small studies which preclude a more comprehensive analysis. We have studied the Surveillance Epidemiology and End Results (SEER) database to determine the rate of and risk factors for distant disease at presentation. Methods: We have identified all patients with the diagnosis of SCCHN who are older than age 20 who have been diagnosed between 1988 and 2003. Patients whose disease extent is not evaluated have been excluded. Tumor sites evaluated include the lip, oral cavity, oropharynx, nasopharynx, sinus, hypopharynx, supraglottis, glottis, and subglottis. In addition, we have determined the effect of lymph node status and primary size on the rate of distant metastases at presentation. We arbitrarily chose a rate of >5% to be high risk for metastasis and a rate of <1% to be low risk. The results were analyzed with binomial confidence intervals. Results: Among the 76,925 patients identified, 2,312 (3.01%; 95% CI: 2.89%-3.13%) had distant metastasis at presentation. The rate of distant metastases increased in relation to tumor size and lymph node status. Tumors at high risk include lip, hypopharynx, supraglottic, glottic, and nasopharynx N2/N3; lymph node positive sinus tumors; oropharynx and oral cavity tumors N3 disease; and sinus, hypopharynx, and oropharynx tumors greater than 4 cm. Tumors with low risk of metastasis include lip, oral cavity, and glottic tumors that are either less than 2 cm or without lymph node involvement. Conclusion: Distant metastasis at presentation is an uncommon event for SCCHN. The primary site, tumor size, and nodal stage all help determine the patients that are at particularly high or low risk for presenting with Stage IVC disease. Site Total in SEER Number Metastatic at Presentation Percentage 95% CI Lip 5,975 20 0.33% 0.20–0.52% Oral Cavity 16,385 320 1.95% 1.75–2.18% Oropharynx 17,783 729 4.10% 3.81–4.40% Hypopharynx 1,866 128 6.86% 5.75–8.10% Supraglottis 8,114 270 3.33% 2.95–3.74% Glottis 13,085 87 0.66% 0.53–0.82% Subglottis 356 12 3.37% 1.75–5.81% Sinus 1,068 69 6.46% 5.06–8.11% Nasopharynx 2,610 177 6.78% 5.85–7.81% No significant financial relationships to disclose.

Laryngeal carcinoma--patient profile and delay in referral.

Aim: The aim of this study was to compile a profile of patients with laryngeal carcinoma presenting to the ENT clinic at Universitas Hospital, Bloemfontein. Methods: Fifty consecutive patients with laryngeal carcinoma were prospectively interviewed and information regarding their symptoms, social habits and delay in referral was recorded. Staging was performed in the operating theatre. Results: Hoarseness was the most common symptom (98%). Sixty-four percent of patients presented with airway obstruction and 26% had a visible neck mass. The median patient delay was 1.5 months, while the median professional delay was 5 months. The median total delay was 7 months. Glottic and supraglottic tumours were the most common at 36% and 34% respectively. Eighty percent of patients were either stage 3 or 4, while only 20% were classified as early cancers (stage 1 and 2). Conclusion: In this study the majority of patients presented with advanced tumours. Both patients and medical professionals did not seem to realize the significance of unrelenting hoarseness as a possible symptom of laryngeal cancer. We propose the initiation of an awareness campaign to address this problem.

Functional vocal results after CO2 laser endoscopic surgery for glottic tumours

Vocal results after endoscopic cordectomy have not yet been well defined. The aim of this study was to assess the vocal function of patients who had undergone CO2 laser cordectomy. Retrospective, observational and control group study, conducted in a tertiary care medical department. One hundred and thirty-five male patients (age range 36-83 years) underwent different types of endoscopic cordectomy. Forty age-matched, euphonic male subjects were selected as controls. Patients were classified according to the main site of the phonatory neo-glottis. Outcome measures were maximum phonation time, vocal intensity and harmonic/noise ratio. Mann-Whitney and rank Spearman tests were used for statistical analysis. Findings indicated statistically significant differences for all parameters, comparing patients and controls (p<0.001), and a direct positive relation between type of functional compensation and outcome measures in the study patients (p<0.001). The results indicate that functional compensation and outcome measures were related, and that no functional compensation enabled the study patients to achieve a voice quality comparable with that of controls.

Evolution of the epidemiology and clinical characteristics of larynx and hypopharynx carcinoma in Poland from 1991 to 2001

A retrospective analysis was performed of 12,888 cases of larynx and hypopharynx carcinoma diagnosed in 19 ENT Departments in Poland during an 11-year period from 1991 to 2001. An assessment of basic epidemiological data, including also tumor site and disease stage at the time of diagnosis, was conducted. Epidemiological trends over the 11-year period of the analysis were examined. The average M:F proportion was 8:1, with a significant increase in the number of female patients during the analyzed period. The predominant localization of carcinoma was in the glottis (47.2%), followed by the supraglottis (40.3%) and pyriform sinus (7.8%). A significant increase in pyriform sinus tumors was observed in the analyzed period. Majority of cases (57.4%) presented with local advanced stage (T3+T4) carcinoma of the larynx and hypopharynx, with the highest rate (81.0%) for the pyriform sinus carcinomas, and with the lowest rate for glottic tumors (41.8%). Regional lymph node metastases were diagnosed in 47.7% of the analyzed cases, with the highest rate (82.2%) in cases of pyriform sinus carcinomas, and the lowest (31.7%) in glottic carcinomas. In the 11-year period, a significant drop in N0 cases and a tendency toward increased rates of N2 and N3 lymph nodes metastases cases of supraglottic carcinoma were observed. Distant metastases at the time of diagnosis were registered in 2.2% of the analyzed cases, with the highest percentage in the posterior pharyngeal wall (7.6%) and pyriform sinus (7.4%) carcinomas.

Glottic versus supraglottic tumors: differential molecular profile

Glottis and supraglottis, although anatomically interconnected, are embryologically distinct. Moreover, squamous cell carcinomas arising from these subsites, differ in terms of epidemiology, risk factors, clinical behaviour and prognosis. This study aims to explore any possible differences between their molecular profiles. We investigated in the two tumor types, the expression of epidermal growth factor receptor (EGFR), nuclear factor-kappaB (NF-kappaB) and retinoid X receptor alpha (RXRalpha), principal signal transducers associated with cancer, as well as cyclooxygenase-2 (COX-2), an enzyme induced in malignant neoplasms. The clinical material includes tumor specimens from 61 patients with laryngeal cancer of glottic or supraglottic origin. Subsite groups were matched for gender, age and histological grade. Paraffin-section immunohistochemistry was performed, to detect the aforementioned molecules. Staining patterns were membranic and cytoplasmic for EGFR, purely cytoplasmic for COX-2, nuclear for RXRalpha and cytoplasmic, as well as nuclear, for NF-kappaB. Intense EGFR and RXRalpha expression was significantly associated with glottic tumor descent (P = 0.011 and 0.001, respectively). No significant relationship was established between neoplasm location and expressions of NF-kappaB, COX-2. Our results show that tumors emerging from the two laryngeal regions, are different with regard to their molecular constitution. Upregulation of EGFR and RXRalpha in carcinomas of the glottis, might be important in the design of subsite-specific chemotherapeutic approaches.

Surgery in the Management of Laryngeal and Hypopharyngeal Carcinoma

Currently, a multitude of treatment options are available for laryngeal and hypopharyngeal carcinoma. Surgery should be considered a viable option in the definitive management of almost all laryngeal and hypopharyngeal tumors, regardless of stage. The characteristics of the primary tumor, as well as the status of the at-risk regional lymph nodes, are critical in the development of a treatment plan. In addition to the patient’s history and physical examination, a comprehensive staging evaluation is required that includes endoscopy, biopsy, and imaging. A patient’s comorbidities and functional status are also important factors to consider during the development of a treatment plan. Surgery as a single modality therapycanbeofferedforearly-stagedisease,andthecombination ofsurgery with adjuvanttherapy(radiotherapywithorwithout chemotherapy) should be used for advanced-stage disease. Surgery also plays a critical role in the management of recurrent or persistent disease, especially after initial nonoperative management. Because survival differences do not exist between surgical and nonsurgical therapies for most clinical scenarios, each patient should undergo a multidisciplinary evaluation to discuss all options before therapy. During the assessment of a laryngeal cancer, the tumor should be classified as either glottic or supraglottic, with isolated subglottic primaries rarely seen. Defining the site of origin, as well as clearly delineating the extent of tumor, is mandatory in developing a surgical plan. Deciding on the surgical options for the primary tumor, as well as whether to address the regional nodal basins, is determined from these tumor characteristics. In general, early glottic tumors are amenable to partial laryngeal resection. Regional metastases are uncommon at presentation and the potential for occult nodal disease is low, making neck dissection usually unnecessary.Moreadvancedglotticprimaries mightstill beamenable to partial laryngeal resection, but total laryngectomy and neck dissection could be required. Supraglottic tumors are also frequently amenable to partial laryngeal resection, but, again, in some instances, total laryngectomy might be required. Most supraglottic tumors, regardless of T stage, require therapy directed to the regional lymph nodes, given the high risk of regional spread. Neck dissection for the regional nodal basin is usually required bilaterally, given the richlymphatics of the supraglottisand the relatively infrequent occurrence of well-lateralized supraglottic primary tumors. Selected laryngeal, as well as hypopharyngeal, carcinomas are best managed by total laryngectomy (with postoperative adjuvant therapy) as the initial treatment. The most common scenario requiring definitive total laryngectomy is a case in which extensive cartilage erosion or extralaryngeal extension of the tumor is present. Patients with these extensive tumors have been shown to have worse disease control when treated by radiotherapy alone compared with surgery and postoperative radiotherapy (1). In the recent multimodality nonoperative organ preservation trials, patients with these extensive T4 tumors were more likely to need salvage laryngectomy or were excluded from participation in the trial (2, 3). The other clinical scenario in which total laryngectomy should be considered is for patients who have life-threatening aspiration at diagnosis. Several surgical organ preservation options exist for laryngeal tumors. These options can beclassified as either openvs. endoscopic procedures. Historically, open laryngeal preservation surgery for glottic tumors included cordectomy or vertical partial laryngectomy and, for supraglottic tumors, included horizontal partial laryngectomy. Near-total laryngectomy has been used for organ preservation in more advanced glottic and supraglottic tumors. Currently, with the success of tracheoesophageal prostheses for speech restoration after total laryngectomy and the success of extended partial laryngeal resection for more advanced tumors, this procedure is rarely performed. More recently, supracricoid laryngectomy and endoscopic laser resection have gained significant popularity in the management of both glottic and supraglottic carcinomas.