Laryngeal dysplasia: Oncological outcomes in a large cohort of patients treated in a tertiary comprehensive cancer centre.

PURPOSE: Laryngeal dysplasia represents a series of precancerous lesions, observed as laryngeal leukoplakia. General agreement has been lacking for their management and treatment ranging from simple biopsy to complete excision with cold blade/laser. In this work, we aim at providing the oncological outcomes of patients affected by laryngeal dysplasia, treated with a single modality, and at identifying clinical parameters predictive of malignant transformation. MATERIALS AND METHODS: We performed a retrospective analysis of patients treated with transoral laser microsurgery between January 2005 and December 2015 in a tertiary comprehensive cancer centre. Data were collected about smoke and alcohol habits, site of the laryngeal lesion, surgical outcomes and progression to invasive squamous cell carcinoma. RESULTS: The grade of dysplasia, margins' status and smoke habit were not associated with a significantly worse DFS and a higher risk of invasive SCC. We identified three parameters (supraglottic involvement, multifocality and history of more than one recurrence of dysplasia) that have a significant prognostic value. CONCLUSIONS: On the base of these clinical parameters, a more intensive follow-up might be warranted for high-risk patients.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Role of thuja in the management of laryngeal papilloma.

Juvenile respiratory laryngeal papillomatosis is a subset of a larger clinical entity of recurrent respiratory papillomatosis. It is characterised by the development of recurrent papillomata in the vocal folds. Human papillomavirus types 6 and 11 has been implicated to be the most common strain of virus associated with the formation of laryngeal papilloma. Clinical diagnosis is based on typical appearance of warty lesion on endoscopy. Surgery is the primary line of management along with adjuvant therapy like antiviral drugs and immunomodulators. Thuja occidentalis is a tree native to North America whose leaves and leaf oil have antiviral, antibacterial and antifungal properties. It has been widely used for the treatment of condylomatous skin lesions and warts. Here we discuss the outcome of thuja as an adjuvant therapy in the treatment of laryngeal papillomatosis in an 8-year-old child.

Fluorescence imaging-guided multifunctional liposomes for tumor-specific phototherapy for laryngeal carcinoma.

Reliable diagnosis and efficient targeted therapy are important and may lead to the effective treatment of laryngeal carcinoma. Multifunctional nano-theranostic agents demonstrate great potential in tumor theranostic applications. Thus, herein, we report novel targeting multifunctional theranostic nanoparticles, internalized RGD (iRGD)-modified indocyanine green (ICG) encapsulated liposomes (iLIPICG), for imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) for the treatment of laryngeal carcinoma. The iRGD-PEG-DSPE lipid endowed iLIPICG with high affinity for tumor vascular targeting, tumor-penetration and tumor cell targeting. The in vivo results showed that iLIPICG exhibited excellent blood circulation and tumor accumulation. iLIPICG could be spatially and temporally controlled, simultaneously producing hyperthermia and reactive oxygen species as well as a fluorescence-guided effect through ICG to ablate laryngeal carcinoma cells under irradiation from an 808 nm laser. iLIPICG generated synergistic photodynamic-photothermal cytotoxicity against Hep-2 cells, resulting in the efficient ablation of laryngeal carcinoma. Thus, the iLIPICG system provides a promising strategy to improve the precision imaging and effective phototherapy for the treatment of laryngeal carcinoma.

Demographic and Tumor Characteristic Impact on Laryngeal Cancer Outcomes in a Minority Underserved Patient Population.

OBJECTIVE: Advanced laryngeal squamous cell carcinoma remains associated with approximately 50% mortality at 5 years. Delivery of multimodality treatment remains critical to maximizing survival for this disease, but achieving this at a national level remains a difficult undertaking, particularly in under- and uninsured patients as well as minority patients. We sought to evaluate laryngeal cancer treatment delivery and clinical outcomes in a predominantly minority and underserved cohort of largely under- and uninsured patients in a county hospital. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care county hospital in Houston, Texas. SUBJECTS AND METHODS: Patients (N = 210) with a new diagnosis of laryngeal squamous cell carcinoma treated between 2005 and 2015 were included in a retrospective analysis of patient demographics, tumor and treatment characteristics, and oncologic outcomes. RESULTS: The majority of patients presented with advanced disease (T4 = 43%, N>0 = 45%). Treatment selection was compliant with National Comprehensive Cancer Network guidelines in 81% of cases, but 76% of patients who required adjuvant radiotherapy were unable to start it within 6 weeks postsurgery. Overall survival and disease-free survival were 52% and 63% for the entire cohort, respectively. Supraglottic subsite and nodal metastases were significantly associated with decreased overall survival and disease-free survival. Race/ethnicity and insurance status were not associated with worse oncologic outcomes. CONCLUSION: Under- and uninsured patients often present with advanced laryngeal cancer. Oncologic outcomes in this cohort of patients is similar to that of other published series. Moreover, tumor characteristics rather than demographic variables drive oncologic outcomes for the predominantly minority and underserved patients seeking care in our tertiary care county hospital.

Immediate effect of neuromuscular electrical stimulation on deglutition after treatment of laryngeal cancer: a case report. / Efeito imediato da estimulação elétrica neuromuscular na deglutição após tratamento do câncer de laringe: relato de caso.

The objective of this study was to verify the immediate effect of sensory and motor neuromuscular electrical stimulation (NMES), in the oral and pharyngeal phases of deglutition, in a 64 year male patient after laryngeal cancer treatment. Videofluoroscopy was performed during deglutition of 5 ml of honey and pudding, under three conditions: without stimulation, with sensory NMES, with motor NMES, randomly defined. The degree of dysfunction of deglutition (DOSS), the presence of food stasis (Eisenhuber scale), laryngeal penetration and laryngotracheal aspiration (PAS) and oral and pharyngeal transit time were evaluated. An evaluator without knowing about the applied stimulus. On the DOSS scale there was improvement with sensory and motor stimulation. In the PAS scale, there was improvement, both for the sensorial and motor stimulus in the honey consistency, but the worsening of the motor stimulus for the pudding consistency was observed. There was reduction of the residues in the base of the tongue with sensorial and motor stimulus for the consistency of pudding and honey; worsening motor stimulus in the posterior wall of the pharynx for honey consistency. There was no difference between stimulation levels regarding to oral and pharyngeal transit time. The results showed that NMES at the sensory and motor levels improved the degree of dysphagia in an individual after the treatment of laryngeal cancer, with greater benefits of the sensory level in relation to the motor regarding to the presence of penetration and residues.

Este trabalho teve por objetivo verificar o efeito imediato da Estimulação Elétrica Neuromuscular (EENM) sensorial e motora, nas fases oral e faríngea da deglutição, em um homem de 64 anos, após tratamento de câncer de laringe. Foi realizado exame de videofluoroscopia durante a deglutição de 5 ml de mel e pudim, em três condições: sem estimulação, com EENM sensorial, com EENM motora, definidas de forma randomizada. Foi classificado o grau da disfunção da deglutição (DOSS), a presença de estase de alimentos (escala de Eisenhuber), de penetração laríngea e aspiração laringotraqueal (PAS), além da medida do tempo de trânsito oral e faríngeo, realizadas por uma avaliadora sem conhecimento sobre o estímulo aplicado. Na escala DOSS, houve melhora com a estimulação sensorial e motora. Na escala PAS, verificou-se melhora, tanto para o estímulo sensorial quanto motor na consistência mel, porém observou-se piora no estímulo motor para a consistência pudim. Houve diminuição dos resíduos em base de língua com estímulo sensorial e motor para as consistências pudim e mel; piora no estímulo motor na parede posterior da faringe para a consistência mel. Em relação ao tempo de trânsito oral e faríngeo, não foi observada diferença entre os níveis de estimulações. Os resultados demonstraram que a EENM em nível sensorial e motor melhorou o grau da disfagia em um indivíduo após o tratamento de câncer de laringe, com maiores benefícios do nível sensorial em relação ao motor no que diz respeito à presença de penetração e resíduos.

Photoacoustic-imaging-guided therapy of functionalized melanin nanoparticles: combination of photothermal ablation and gene therapy against laryngeal squamous cell carcinoma.

Multimodality therapy under imaging-guidance is significant to improve the accuracy of cancer treatment. In this study, a photoacoustic imaging (PAI)-guided anticancer strategy based on poly-l-lysine functionalized melanin nanoparticles (MNP-PLL) was developed to treat laryngeal squamous cell carcinoma (LSCC). As a promising alternative to traditional therapies for LSCC, MNP-PLL/miRNA nanoparticles were combined with photothermal ablation against primary tumors and miR-145-5p mediated gene therapy for depleting the metastatic potential of tumor cells. Furthermore, taking advantage of the photoacoustic properties of melanin, PAI guided therapy could optimize the time point of NIR irradiation to maximize the efficacy of photothermal therapy (PTT). The in vitro and in vivo results proved that the combined treatments displayed the most significant tumor suppression compared with monotherapy. By integrating thermo-gene therapies into a theranostic nanoplatform, the MNP-PLL/miR-145-5p nanoparticles significantly suppressed the LSCC progression, indicating their great potential use for cancer therapy.

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma.

BACKGROUND: We sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene-specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA). METHODS: The tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene-specific alteration frequencies were compared (Chi-Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform. RESULTS: Persistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53. CONCLUSIONS: Our results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.

Disparities in adherence to head and neck cancer follow-up guidelines.

OBJECTIVES: In this study, we aim to determine the frequency of adherence to National Comprehensive Cancer Network follow-up guidelines in a population of head and neck cancer patients who received curative treatment. We will also assess the impact of race, ethnicity, socioeconomic status, and treatment setting on utilization of follow-up care. METHODS: This study included patients with biopsy-proven, nonmetastatic oropharyngeal or laryngeal cancer treated with radiotherapy between January 1, 2014, and June 30, 2016, at a safety-net hospital or adjacent private academic hospital. Components of follow-up care analyzed included an appointment with a surgeon or radiation oncologist within 3 months and posttreatment imaging of the primary site within 6 months. Univariable and multivariable analyses were conducted using a logistic regression model to estimate odds ratios and corresponding 95% confidence intervals. RESULTS: Two hundred and thirty-four patients were included in this study. Of those, 88.8% received posttreatment imaging of the primary site within 6 months; 88.5% attended a follow-up appointment with a radiation oncologist within 3 months; and 71.1% of patients attended a follow-up appointment with a surgeon within 3 months. On multivariable analysis, private academic hospital treatment versus safety-net hospital treatment was associated with increased utilization of both surgical and radiation oncology follow-up. Non-Hispanic black (NHB) patients, Hispanic patients, and those with a low socioeconomic status were also less likely to receive follow-up. CONCLUSION: Safety-net hospital treatment, socioeconomic status, Hispanic ethnicity, and NHB race were associated with decreased follow-up service utilization. Quality improvement initiatives are needed to reduce these disparities. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2303-2308, 2019.

Efeito imediato da estimulação elétrica neuromuscular na deglutição após tratamento do câncer de laringe: relato de caso / Immediate effect of neuromuscular electrical stimulation on deglutition after treatment of laryngeal cancer: a case report

RESUMO Este trabalho teve por objetivo verificar o efeito imediato da Estimulação Elétrica Neuromuscular (EENM) sensorial e motora, nas fases oral e faríngea da deglutição, em um homem de 64 anos, após tratamento de câncer de laringe. Foi realizado exame de videofluoroscopia durante a deglutição de 5 ml de mel e pudim, em três condições: sem estimulação, com EENM sensorial, com EENM motora, definidas de forma randomizada. Foi classificado o grau da disfunção da deglutição (DOSS), a presença de estase de alimentos (escala de Eisenhuber), de penetração laríngea e aspiração laringotraqueal (PAS), além da medida do tempo de trânsito oral e faríngeo, realizadas por uma avaliadora sem conhecimento sobre o estímulo aplicado. Na escala DOSS, houve melhora com a estimulação sensorial e motora. Na escala PAS, verificou-se melhora, tanto para o estímulo sensorial quanto motor na consistência mel, porém observou-se piora no estímulo motor para a consistência pudim. Houve diminuição dos resíduos em base de língua com estímulo sensorial e motor para as consistências pudim e mel; piora no estímulo motor na parede posterior da faringe para a consistência mel. Em relação ao tempo de trânsito oral e faríngeo, não foi observada diferença entre os níveis de estimulações. Os resultados demonstraram que a EENM em nível sensorial e motor melhorou o grau da disfagia em um indivíduo após o tratamento de câncer de laringe, com maiores benefícios do nível sensorial em relação ao motor no que diz respeito à presença de penetração e resíduos.

ABSTRACT The objective of this study was to verify the immediate effect of sensory and motor neuromuscular electrical stimulation (NMES), in the oral and pharyngeal phases of deglutition, in a 64 year male patient after laryngeal cancer treatment. Videofluoroscopy was performed during deglutition of 5 ml of honey and pudding, under three conditions: without stimulation, with sensory NMES, with motor NMES, randomly defined. The degree of dysfunction of deglutition (DOSS), the presence of food stasis (Eisenhuber scale), laryngeal penetration and laryngotracheal aspiration (PAS) and oral and pharyngeal transit time were evaluated. An evaluator without knowing about the applied stimulus. On the DOSS scale there was improvement with sensory and motor stimulation. In the PAS scale, there was improvement, both for the sensorial and motor stimulus in the honey consistency, but the worsening of the motor stimulus for the pudding consistency was observed. There was reduction of the residues in the base of the tongue with sensorial and motor stimulus for the consistency of pudding and honey; worsening motor stimulus in the posterior wall of the pharynx for honey consistency. There was no difference between stimulation levels regarding to oral and pharyngeal transit time. The results showed that NMES at the sensory and motor levels improved the degree of dysphagia in an individual after the treatment of laryngeal cancer, with greater benefits of the sensory level in relation to the motor regarding to the presence of penetration and residues.

From VA Larynx to the future of chemoselection: Defining the role of induction chemotherapy in larynx cancer.

Organ preservation protocols utilizing induction chemotherapy as a selection agent have played a critical role in the treatment of advanced laryngeal squamous cell carcinoma (LSCC). The selection of patients who will have a good response to chemoradiation allows for organ preservation in a significant group of patients and minimizes the rate of surgical salvage. While there remains debate regarding its utility when compared to surgery or other organ preservation regimens, the data does suggest an important role for induction chemotherapy in LSCC. In addition, there are continued opportunities to identify pretreatment biomarkers for induction chemotherapy, whether genetic, epigenetic or cellular, that could predict response to treatment and select patients to therapy (whether organ preservation or surgery). As our understanding of the biology of larynx cancer advances, induction paradigms have utility for the development and adoption of novel agents and therapeutics. The background of induction chemotherapy as a selection agent and future directions of this approach are discussed.

Postoperative (chemo) radiation in patients with squamous cell cancers of the head and neck - clinical results from the cohort of the clinical cooperation group "Personalized Radiotherapy in Head and Neck Cancer".

BACKGROUND: Postoperative (chemo) radiation improves tumor control and survival in high-risk patients with head and neck squamous cell carcinoma based on established risk factors. The clinical cooperation group "Personalized Radiotherapy in Head and Neck Cancer" focuses on the identification and validation of new biomarkers, which are aimed at eventually stratifying and personalizing the therapy concept. Hence, we reviewed all patients with head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, treated with postoperative (chemo) radiation from 06/2008 until 06/2015 at the Department of Radiation Oncology in the University Hospital, LMU Munich. Here we report the clinical results of the cohort, laying the foundation for further research within the framework of a clinical cooperation group. METHODS: Patient data were retrospectively (until 2013) and prospectively (from 2013) collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors. RESULTS: We identified 302 patients (median follow-up 45 months, average age 60.7 years), having received postoperative (chemo)radiation (median 64 Gy). Chemotherapy was added in 58% of cases, mostly Cisplatin/5- Fluorouracil in concordance with the ARO 96-3 study. The 3-year overall survival, local, locoregional and distant failure estimates were 70.5, 9.7, 12.2 and 13.5%, respectively. Human papillomavirus-associated oropharyngeal cancer was associated with a significant improved overall survival, locoregional, distant and overall tumor control rates in multivariate analysis. Additionally, in multivariate analysis, for local failure, resection status and perineural invasion, for locoregional and distant failure extracapsular extension and for overall survival the presence of nodal disease were significant adverse factors. Moreover, 138 patients have been treated in concordance with the ARO 96-3 protocol, corroborating the results of this study. CONCLUSIONS: Our cohort represents a large unselected cohort of patients with head and neck squamous cell carcinoma treated with postoperative (chemo)radiation. Tumor control rates and survival rates are consistent with the results of previously reported data.

Effect of neuromuscular electrical stimulation for fatigue management in patients with advanced laryngeal cancer receiving chemoradiotherapy.

This study retrospectively investigated the effect of neuromuscular electrical stimulation (NMES) for fatigue management in patients with advanced laryngeal cancer (ALC) receiving chemoradiotherapy.A total of 60 eligible patients with ALC receiving chemoradiotherapy were included. These patients were assigned equally to a treatment group and a control group. Patients in the treatment group received NMES therapy and were treated for a total of 8 weeks, while the patients in the control group did not receive NMES therapy. The primary outcome was fatigue, measured by the multidimensional fatigue inventory (MFI). The secondary outcomes included anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS), and sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI). All outcomes were evaluated before and after 8-week NMES treatmentAfter 8-week NMES treatment, the patients in the treatment group did not exert better effect than patients in the control group in fatigue relief, measured by the MFI score, anxiety and depression decrease, assessed by HADS, and sleep quality improvement, evaluated by PSQI.The results of this study demonstrate that NMES may not benefit for fatigue relief in patients with ALC receiving chemoradiotherapy. Future studies should still focus on this topic and warrant these results.

AHNS Series - Do you know your guidelines? Principles of treatment for glottic cancer: A review of the National Comprehensive Cancer Network guidelines.

This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network (NCCN) guidelines for primary and adjuvant treatment of cancer of the glottic larynx are reviewed here in a systematic fashion according to stage.

Evaluation of Quality Metrics for Surgically Treated Laryngeal Squamous Cell Carcinoma.

Importance: Quality metrics for patients with laryngeal squamous cell carcinoma (SCC) exist, but whether compliance with these metrics correlates with improved survival is unknown. Objective: To examine whether compliance with proposed quality metrics is associated with improved survival in patients with laryngeal SCC treated with surgery with or without adjuvant therapy. Design, Setting, and Participants: This retrospective cohort study included patients from a tertiary care academic medical center who had previously untreated laryngeal SCC and underwent surgery with or without adjuvant therapy from January 1, 2003, through December 31, 2012. Data analysis was performed from August 4, 2015, through December 13, 2015. Interventions: Surgery with or without adjuvant therapy. Main Outcomes and Measures: Compliance with quality metrics from the American Head and Neck Society (AHNS), National Comprehensive Cancer Network (NCCN) guidelines, and institutional metrics with face validity covering pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. The association between compliance with the group of metrics and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) was explored using Cox proportional hazards analysis. The association between compliance with individual metrics and survival was similarly determined. Results: A total of 243 patients (184 men and 59 women) were included in the study (median age, 62 years; age range, 23-87 years). No association was found between increasing levels of compliance with the AHNS or NCCN metrics and survival. The only AHNS or NCCN metric for which greater compliance correlated with improved survival on multivariable Cox proportional hazards analysis controlling for pT stage, pN stage, extracapsular spread, margin status, and comorbidity was pretreatment multidisciplinary evaluation for patients with stage cT3-4 or cN1-3 disease (OS adjusted hazard ratio [aHR], 0.47; 95% CI, 0.24-0.94; DFS aHR, 0.45; 95% CI, 0.23-0.85). For the institutional metrics, multidisciplinary evaluation for all patients (OS aHR, 0.51; 95% CI, 0.29-0.88; DFS aHR, 0.50, 95% CI, 0.32-0.80) and elective neck dissection yield of 18 lymph nodes or more (DFS aHR, 0.36; 95% CI, 0.14-0.99) were associated with improved survival on multivariable Cox proportional hazards analysis. Conclusions and Relevance: In this cohort of patients with surgically treated laryngeal SCC, multidisciplinary evaluation and elective neck dissection yield of 18 lymph nodes or more are associated with improved survival. Development of better quality metrics is necessary because increased compliance with metrics described by the AHNS and NCCN is not associated with improved survival. Previously described metrics for surgically treated oral cavity cancer are not prognostic for surgically treated laryngeal SCC. Future multi-institutional collaboration will be required to validate these findings, develop better quality metrics, and evaluate whether quality metrics for head and neck cancer are site specific.

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy.

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma.

PURPOSE: The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. MATERIALS AND METHODS: After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. RESULTS: Ad-p14(ARF) combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. CONCLUSION: Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided.

Combined chemoradiotherapy with local microwave hyperthermia for treatment of T3N0 laryngeal carcinoma: a retrospective study with long-term follow-up.

The purpose of our study was to test the efficacy and toxicity of hyperthermia in conjunction with chemoradiotherapy for T3N0 laryngeal cancer. From 1997-2006, 25 patients diagnosed with T3N0 laryngeal carcinoma who denied laryngectomy were selected for this retrospective study. Patients received a total dose of 70 Gy (2 Gy per fraction, 5 days per week) in combination with 6 weekly sessions of hyperthermia, in addition to weekly cisplatin chemotherapy. The hyperthermia device was operated as a 433 MHz microwave heating with water loaded and water-cooled waveguides. The temperature was monitored subcutaneously in the skin under the aperture of the waveguide. The median follow-up was 60 months, while 23 of 25 patients (92%) presented complete response to treatment. The two patients that did not respond to thermoradiotherapy underwent total laryngectomy, and during follow-up were alive and free of disease. According to EORTC/RTOG criteria, toxicity was mild: three patients (12%) presented grade III, eight (32%) presented grade II and 14 (56%) presented grade I acute skin toxicity. Grade III laryngeal late toxicity (vocal cord malfunction due to severe oedema) was noted in two patients (8%) at 6-8 months post-thermo-chemoradiotherapy. Tmin was correlated (Spearman rho, p < 0.05) with response to treatment as well as with acute skin toxicity and laryngeal function. When a patient with T3N0 laryngeal carcinoma denies laryngectomy, an alternative treatment is combined thermo-chemoradiotherapy which seems to be effective and generally tolerable with radiation-induced skin toxicity and/or late side effects. A larger patient cohort is needed to confirm these results.

Subglottic extramedullary plasmacytoma with light chain multiple myeloma masquerading as adult-onset asthma.

Extramedullary plasmacytoma (EMP) arises outside the bone marrow and can be associated with multiple myeloma (MM). A 55-year-old gentleman, who presented with dyspnea and expiratory wheeze, was diagnosed and treated for asthma. A subsequent relapse 6 months later prompted an Otolaryngology consult. Preliminary findings showed a benign-looking nodular lesion at the subglottis. Work-up at our institution revealed an Fludeoxyglucose (FDG) avid left subglottic lesion with multiple bone metastases on a Positron Emission Tomography / Computed Tomography (PET/CT). The patient underwent a panendoscopy and laser excision of the subglottic lesion with subglottic jet ventilation. Histology showed an EMP. Further work-up revealed the presence of kappa light chain MM with adverse cytogenetics. Patient was treated systemically with lenalidomide, bortezomib, and dexamethasone for four cycles with rapid improvement in his symptoms. We review the literature about EMP of the subglottis with MM. We present the first case of subglottic laryngeal EMP with MM managed via CO2 laser excision.