Mortalidade e carga do câncer de laringe atribuíveis aos riscos ocupacionais no Brasil: estudo da Carga Global de Doença, 2019 / Laryngeal cancer mortality and burden attributable to occupational risks in Brazil: 2019 Global Burden of Disease

Resumo Objetivo: descrever a mortalidade e os anos de vida ajustados pela incapacidade disability-adjusted life years - DALYs) para câncer de laringe no Brasil atribuíveis a fatores de risco ocupacionais e comportamentais. Métodos: estudo ecológico com dados do estudo Global Burden of Disease 2019. Foram obtidas taxas de mortalidade e de DALYs para o câncer de laringe atribuíveis aos riscos ocupacionais (ácido sulfúrico e amianto) e comportamentais (tabaco e álcool), de 1990 e 2019. Resultados: no Brasil, em 2019, a taxa de mortalidade por câncer de laringe atribuível aos riscos ocupacionais (ácido sulfúrico e amianto) foi 0,28 (II95%: 0,17;0,43) no sexo masculino e 0,03 (II95%: 0,02;0,04) no feminino, e a de DALYs foi 7,33 (II95%: 4,28;11,44) e 0,64 (II95%: 0,35;0,03), respectivamente. O ácido sulfúrico foi o principal risco ocupacional para a doença. Houve redução das taxas atribuíveis ao tabaco (mortalidade:-45,83%; DALYs:-47,36%) e aos riscos ocupacionais (mortalidade:-23,20%; DALYs:-26,31%), no Brasil, com aumento em alguns estados das regiões Norte e Nordeste. Conclusão: houve redução na mortalidade e na carga do câncer de laringe atribuível aos fatores ocupacionais no período, porém menor em comparação ao tabagismo, reforçando a importância de ações para reduzir o impacto dos riscos ocupacionais, como as medidas regulatórias aplicadas ao tabaco.

Abstract Objective: to describe mortality and disability-adjusted life years (DALYs) due to laryngeal cancer attributable to occupational and behavioral risk factors in Brazil. Methods: this is an ecological study with data from the 2019 Global Burden of Disease. Mortality and DALY rates for laryngeal cancer attributable to occupational (sulfuric acid and asbestos) and behavioral (tobacco and alcohol) risks were obtained from 1990 and 2019. Results: in 2019, the mortality rate from laryngeal cancer attributable to occupational hazards (sulfuric acid and asbestos) totaled 0.28 (95%UI: 0.17; 0.43) and 0.03 (95%UI: 0.02; 0.04), whereas and DALY rates, 7.33 (95%UI: 4.28; 11.44) and 0.64 (95%UI: 0.35; 0.03) in men and women in Brazil, respectively. Sulfuric acid configured the main occupational risk for the disease. The rates attributable to tobacco (mortality: −45.83%; DALYs: −47.36%) and occupational hazards (mortality: −23.20%; DALYs: −26.31%) decreased in Brazil but increased in some Northern and Northeastern states. Conclusion: laryngeal cancer mortality and burden attributable to occupational factors decreased in the period (although less than that for smoking), reinforcing the importance of actions to reduce the impact of occupational risks, such as the regulatory measures applied to tobacco.

Neurofibromatosis laríngea pediátrica: reporte de localización atípica / Pediatric neurofibromatosis of the larynx: report of atypical location

Los neurofibromas laríngeos (NFL) son tumores benignos poco frecuentes de localización principalmente supraglótica. Se manifiestan con síntomas obstructivos de la vía aérea. El tratamiento es la resección completa del tumor mediante abordaje endoscópico; se reserva la cirugía abierta para tumores de gran extensión. Se presenta el caso de un paciente pediátrico con localización atípica de NFL asociado a neurofibromatosis tipo 1 (NF1). Se realizó resección endoscópica del tumor y la anatomía patológica informó neurofibroma plexiforme. Es importante sospechar de esta patología en todo niño con estridor inspiratorio atípico progresivo. Se sugiere seguimiento a largo plazo por la alta probabilidad de recidiva.

Laryngeal neurofibromas (LNFs) are rare benign tumors mainly located in the supraglottis. LNFs occur with airway obstruction symptoms. The treatment is complete resection via an endoscopic technique; the open approach is reserved for large tumors. Here we describe the case of a pediatric patient with LNF of atypical location associated with neurofibromatosis type 1 (NF-1). The tumor was resected with an endoscopic technique, and the pathological study reported a plexiform neurofibroma. It is important to suspect this condition in any child with atypical, progressive inspiratory stridor. Long-term follow-up is recommended due to the high rate of recurrence

COVID-19 en pacientes oncológicos / COVID-19 in cancer patients

Introducción: La Organización Mundial de la Salud declaró el COVID-19 como una pandemia el 11 de marzo de 2020. El antecedente de cáncer es considerado un factor de riesgo de mortalidad para múltiples padecimientos; la evolución de los pacientes con enfermedades neoplásicas puede verse influida por afecciones sobreañadidas como fue el caso del COVID-19. Objetivo: Caracterizar, desde el punto de vista clínico, a los pacientes oncológicos que ingresaron con COVID-19. Métodos: Se realizó una investigación descriptiva y transversal en pacientes con diagnóstico de enfermedad oncológica ingresados por COVID-19, en el Hospital Universitario Dr. Celestino Hernández Robau, Villa Clara, en el período de enero-diciembre 2021. Se incluyeron en el estudio 78 pacientes con diagnóstico de neoplasia de 5 años o menos de evolución. Resultados: Predominó el sexo masculino y los mayores de 60 años de edad. El 39,7 % de los pacientes presentó cáncer de pulmón o de laringe seguido por cáncer de mama, hemolinfopoyético y colorrectal. El 46,2 % se encontraba en estadio estable y el 29,5 % en paliativo. El 34,6 % de los pacientes recibía tratamiento con quimioterapia en el momento del ingreso. Los fármacos más utilizados fueron: esteroides (85,9 %), interferón alfa (73,1 %) y heparina sódica (55,1 %). Conclusiones: En los pacientes oncológicos hospitalizados con COVID-19, los tumores de pulmón y laringe fueron los más frecuentes, aunque el de mama, próstata y colorrectal, en ese orden, se relacionaron con mayor mortalidad. Los pacientes que se encontraban en progresión de la enfermedad y los que recibían tratamiento con quimioterapia presentaron mayor probabilidad de morir.

Introduction: the World Health Organization declared COVID-19 as a pandemic on March 11, 2020. A history of cancer is considered a mortality risk factor for multiple diseases; the evolution in patients with neoplastic diseases can be influenced due to superadded conditions such as the case of COVID-19. Objective: to characterize, from a clinical point of view, cancer patients admitted with COVID-19. Methods: a descriptive and cross-sectional research was carried out in cancer patients admitted with COVID-19 at "Dr. Celestino Hernández Robau" University Hospital in Villa Clara from January to December 2021. A number of 78 cancer patients with 5 years or less of evolution was included in the study. Results: male gender and those over 60 years of age predominated. The 39.7% of the patients had lung or laryngeal cancer followed by breast, hemolymphopoietic and colorectal cancers. The 46.2% were in a stable state and 29.5% in palliative care. The 34.6% of them were receiving chemotherapy treatment at the time of admission. Steroids (85.9%), alpha interferon (73.1%) and sodium heparin (55.1%) were the most used drugs. Conclusions: lung and laryngeal tumours were the most common malignancy in cancer patients hospitalized with COVID-19, although breast, prostate, and colorectal tumours, in that order, were associated with higher mortality. Patients with disease progression and those receiving chemotherapy were more likely to die.

Combined larynx large cell neuroendocrine and squamous cell carcinoma: a case report

ABSTRACT Laryngeal cancer ranks third among the most common head and neck neoplasms. The most common histological subtype is squamous cell carcinoma, and neuroendocrine tumors are rare. An even rarer entity is a composite tumor with both these histologies. This case reports a metastatic combined carcinoma of squamous cells and large neuroendocrine cells, presenting favorable response to treatment with a total laryngectomy followed by adjuvant therapy including chemo-, radio-, and immunotherapy.

Expression of p21-activated kinase 2 in laryngeal squamous cell carcinoma and its correlation with clinicopathological characteristics and chemosensitivity / 肿瘤研究与临床

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.

Treatment Results for Stage III Laryngeal Cancer: Analysis of a Populational Database Using Propensity Scores

Abstract Introduction Treatment of stage III laryngeal cancer suffered a major paradigm change with surgery being substituted by radiation therapy with chemotherapy. Objective To evaluate the oncological outcome of different treatment modalities for stage III laryngeal cancer using a population database. Methods A population database representing patients treated in the state of São Paulo, Brazil, was analyzed. Demographic, clinical and treatment variables were included, and the outcomes of interest were disease-specific and overall survival. Propensity score with nearest neighbor matching was used to compensate for imbalances in treatment groups. Results We retrieved data from 1,804 patients. In multivariate analysis, age, female gender, payment source, clinical N stage (cN) stages, and treatment modality were significant for disease-specific and overall survival. Patients submitted to surgery treatment had a significantly better disease-specific (p < 0.001) and overall survival (p <0.001) compared with chemoradiation. Propensity score matching was based on cN stage, gender, age, topography, and payment modality, and allowed the pairing of 685 patients from each treatment modality. There was a significant difference in disease-specific survival favoring surgery-based treatment (p = 0.017). Conclusion The treatment choice has a significant impact on survival in patients with stage III laryngeal cancer with surgery-based treatment being superior to chemoradiotherapy (CRT).

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study

Abstract Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy (p =0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p <0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Tumor miofibroblástico inflamatorio de laringe: a propósito de un caso / Inflammatory myofibroblastic tumor of the larynx: a case report

Resumen El tumor miofibroblástico inflamatorio (TMI) es una patología muy poco frecuente. Los TMI localizados en laringe pueden ocasionar disfonía o sensación de cuerpo extraño. El diagnóstico se realiza a través de pruebas de imagen y visualización directa con obtención de muestras para estudio histopatológico. Presentamos el caso de una mujer de 43 años, con antecedentes personales de carcinoma indiferenciado de nasofaringe, tratado con radioterapia y quimioterapia, que acude a revisiones periódicas en consulta de otorrinolaringología. Se objetiva por nasofibroscopia una lesión rugosa en cuerda vocal izquierda. Se realiza biopsia con fibroscopio de canal, compatible con tumoración fusocelular atípica, con áreas celulares y mixoides, sospechosa de malignidad, con necesidad de completar estudio inmunohistoquímico. En comité de tumores de cabeza y cuello se decide cirugía programada (laringectomía supracricoidea con cricohioidoepiglotopexia) y posterior tratamiento adyuvante con quimioterapia y/o radioterapia, según resultados del estudio histopatológico. Como conclusión, el TMI es una patología que se encuentra predominantemente en el pulmón, siendo rara la afectación laríngea. Su pronóstico es favorable y el diagnóstico histopatológico es de vital importancia. El diagnóstico correcto va seguido de una escisión local amplia para prevenir la recurrencia, sin embargo, el tratamiento debe adaptarse a la ubicación del tumor y al estado del paciente.

Abstract Inflammatory myofibroblastic tumor (IMT) is a very rare pathology. IMTs located in the larynx can cause dysphonia or foreign body sensation. The diagnosis is made through imaging tests and direct visualization and confirmation with samples for histopathological study. We present the case of a 43-year-old woman with a personal history of undifferentiated carcinoma of the nasopharynx treated with radiotherapy and chemotherapy, who attended periodic check-ups in an otolaryngology clinic. A rough granulomatous lesion was observed by nasofibrolaryngoscopy in the left vocal cord. A canal fibroscope biopsy is performed, compatible with an atypical spindle cell tumor, with cellular and myxoid areas, suspicious of malignancy, requiring an immunohistochemical study to be completed. The head and neck tumor committee decides on scheduled surgery (supracricoid laryngectomy with cricohyoidoepiglottopexy) and subsequent adjuvant treatment with chemotherapy and/or radiotherapy, according to the results of the histopathological study. As a conclusion finally, the IMT is a pathology found predominantly in the lung, laryngeal involvement being rare. Its prognosis is favorable and the histopathological diagnosis is of vital importance to be able to be differentiated from other malignant neoplasms. The correct diagnosis is followed by a wide local excision to prevent recurrence, however, treatment must be tailored to the location of the tumor and the condition of the patient.

Tendência temporal da mortalidade por câncer de laringe no Brasil e regiões, no período de 1980 a 2019 / Temporal trend of larynx cancer mortality in Brazil and regions, from 1980 to 2019

Objetivo: analisar a tendência da mortalidade por câncer de laringe no Brasil e regiões no período de 1980 a 2019. Metodologia: trata-se de um estudo ecológico de série temporal. Os dados foram provenientes do SIM/DATASUS, e foram estratificados segundo faixa etária, ano, local e sexo. Foi calculada a taxa padronizada de mortalidade (TPM) e utilizada para análise de tendência, por intermédio do modelo JoinPoint. Resultados: foi possível observar que o Brasil apresentou alto número de mortes em toda série temporal com cerca de 112.693 óbitos. No tocante as suas regiões destacaram-se o Sudeste, seguido do Sul com 62.111 e 23.356 mortes pelo agravo, respectivamente. Dentre as faixas etárias analisadas, o grupo de 60-79 anos apresentou predominância em ambos os sexos, com 56.947 ocorrências. Já para o sexo, o masculino apresentou mais de 98 mil mortes em detrimento de mais de 13 mil para o feminino, uma diferença 85,6%. Avaliando a tendência, o Brasil apresentou estabilidade em boa parte da série temporal, com diminuição significativa a partir de 2009 (APC -1,6). Nas regiões, o Nordeste apresentou a maior tendência de crescimento (AAPC 2,7) e o Norte também demonstrou crescimento a partir de 1990 (APC 1,8), as demais apresentaram redução considerável e significativa, exceto Centro-oeste que não apresentou JoinPoints. Conclusão: ressalta-se a importância da revisão, melhoria e até implementação de novas políticas de rastreamento a fim de aumentar o quantitativo de diagnóstico precoce e evitar, a longo prazo, a mortalidade.

Objective: to analyze the trend of mortality from laryngeal cancer in Brazil and regions from 1980 to 2019. Methods: this is an ecological time series study. Data came from SIM/DATASUS, and were stratified according to age group, year, location and sex. Age Standard Rates (ASR) were calculated and these were used for trend analysis, performed using the Joinpoint model. Results: it was possible to observe that Brazil had a high number of deaths in the entire time series, with about 112,693 deaths. Regarding its regions, the Southeast stood out, followed by the South with 62,111 and 23,356 deaths from the disease, respectively. Among the age groups analyzed, the 60-79 age group showed a predominance in both sexes, with 56,947 occurrences. As for gender, males had more than 98 thousand deaths at the expense of more than 13 thousand for females, a difference of 85.6%. Assessing the trend, Brazil showed stability in most of the time series, with a significant decrease as of 2009 (APC -1.6). In the regions, the Northeast showed the greatest growth trend (AAPC 2.7) the North also showed growth from 1990 (APC 1.8), the others showed a considerable and significant reduction, except for the Midwest, which did not present Joinpoints. Conclusion: we emphasize the importance of reviewing, improving and even implementing new screening policies in order to increase the number of early diagnoses and prevent, in the long term, mortality.

Effects of hyperthermia on biological behavior of human laryngeal cancer Hep-2 cisplatin-resistant cell line / 肿瘤研究与临床

Objective:To investigate the effects of hyperthermia on the biological behavior of human laryngeal cancer Hep-2 cisplatin-resistant (Hep-2/CDDP) cell line and its possible mechanism.Methods:Hep-2/CDDP cell line was induced by high impact combined with increasing concentration method. Cell count method was used to detect the cell proliferation ability of Hep-2 parental cell group (Hep-2 cells without cisplatin-resistance and the cells were cultured with RPMI 1640 cultured medium without cisplatin), Hep-2/CDDP cell group and Hep-2/CDDP+cisplatin group (using RPMI 1640 cultured medium including 4 mg/L cisplatin). Hep-2/CDDP cell group and Hep-2 parental cell group were treated with cultured medium including 0, 0.004, 0.04, 0.4, 4, 40 mg/L cisplatin, respectively. The sensitivity of Hep-2/CDDP cells to cisplatin, vincristine and 5-fluorouracil was determined by using methyl thiazolyl tetrazolium (MTT) method. The half inhibitory concentration ( IC50) and resistance index (RI) were also calculated. Hep-2/CDDP cell group was divided into 4 subgroups: the cells in the control group were cultured for 24 h at 37 ℃; the cells in hyperthermia group were treated at 43 ℃ for 2 h and then re-cultured at 37 ℃ for 22 h; the cells in cisplatin group were cultured at 37 ℃ for 24 h in cultured medium containing 4 mg/L cisplatin. The cells in hyperthermia combined with cisplatin group were cultured in cultured medium containing 4 mg/L cisplatin, treated at 43 ℃ for 2 h and then re-cultured at 37 ℃ for 22 h. The effects of hyperthermia combined with cisplatin on the proliferation and early apoptosis of Hep-2/CDDP cells were detected by using MTT and flow cytometry. The interaction of hyperthermia combined with cisplatin on the proliferation and early apoptosis of HEP-2/CDDP cells was observed by using factorial analysis. Western blotting was used to detect the effect of hyperthermia combined with cisplatin on the expressions of wild-type p53 and PI3K in Hep-2/CDDP cells. Hep-2/CDDP cells were divided into 4 groups: the control group (Hep-2/CDDP cells were cultured for 24 h at 37 ℃); chemotherapy group was treated with 12 mg/L vincristine or 9 mg/L 5-fluorouracil; in the hyperthermia group, Hep-2/CDDP cells were treated at 43℃ for 2 h and then re-cultured at 37 ℃ for 22 h; in hyperthermia combined with chemotherapy group, the cells were cultured in a medium containing 12 mg/L vincristine or 9 mg/L 5-fluorouracil, treated at 43 ℃ for 2 h and then re-cultured at 37 ℃ for 22 h. MTT method was used to detect the effect of hyperthermia combined with vincristine and 5-fluorouracil on the proliferation of Hep-2/CDDP cells. Results:Hep-2/CDDP cell line was successfully established. There were no significant differences in the number of cells in Hep-2/CDDP cell group, Hep-2 parental cell line group and Hep-2/CDDP + cisplatin cell group at different time points (all P > 0.05), and the doubling time was 43.8, 40.6 and 43.5 h, respectively. The IC50 of Hep-2 parental cell line group and Hep-2/CDDP cell group to cisplatin was 4.771 mg/L and 42.749 mg/L, respectively, and the RI was 8.960. Hyperthermia combined with cisplatin could inhibit the proliferation of Hep-2/CDDP cells ( F = 327.91, P < 0.05) and promote the early apoptosis of Hep-2/CDDP cells ( F = 724.63, P < 0.05). Factorial analysis showed that hyperthermia combined with cisplatin had an interaction effect on the proliferation and early apoptosis of Hep-2/CDDP cells ( F = 185.68, 472.51, all P < 0.05). Western blotting showed that the relative expression levels of wild-type p53 protein and PI3K protein in the control group, hyperthermia group, cisplatin group and hyperthermia combined with cisplatin group were significantly different ( F = 547.76, 404.44, all P < 0.01). Hyperthermia combined with vincristine or 5-fluorouracil could inhibit the proliferation of Hep-2/CDDP cells ( F = 33.06, 34.61, all P < 0.05). Factorial analysis showed that hyperthermia combined with vincristine and 5-fluorouracil had no interaction effect on the proliferation of Hep-2/CDDP cells ( F = 0.64,0.60, all P > 0.05). Conclusions:Hyperthermia may reverse the resistance of Hep-2/CDDP cell line to cisplatin by upregulating wild-type p53 expression and inhibiting the PI3K pathway. Hep-2/CDDP cell line has cross-resistance to vincristine and 5-fluorouracil. Hyperthermia can increase the sensitivity of Hep-2/CDDP cell line to vincristine and 5-fluorouracil.

A nomogram based on dual-energy CT enhanced imaging for prediction of postoperative recurrence of early-stage glottic carcinoma / 中华放射学杂志

Objective:To explore the value of nomogram based on dual-energy CT (DECT) enhanced imaging in predicting postoperative recurrence-free survival (RFS) of early-stage glottic carcinoma (EGC).Methods:The clinicopathological and DECT data of patients with EGC confirmed by pathology in the Tianjin First Central Hospital from January 2015 to July 2018 were analyzed retrospectively. A total of 178 patients were enrolled, including 162 males and 16 females, with the age from 44 to 86 (62±9) years old. According to the follow-up data, the patients were divided into recurrent group ( n=32) and non-recurrent group ( n=146). The differences of clinicopathological data and DECT iodine maps parameters between the two groups were analyzed using χ 2 test, independent-sample t test and Mann-Whitney U test. The survival related cut-off values of the quantitative data between the two groups were selected by X-tile software. The survival curve was drawn using Kaplan-Meier method, and the difference of survival rate was tested with log-rank analysis. The variables with statistical differences were included in the Cox proportional hazard model for multivariate analysis to select the independent predictors of postoperative RFS. Based on the multivariate Cox analysis, the nomogram was drawn to predict the RFS at 1, 2 and 5 years. The prediction efficiency and clinical benefit of the nomogram were evaluated by C-index, calibration curve and decision curve analysis. Results:The median follow-up time was 24.3 months, ranging from 2 to 63 months. There was a significant difference in T-stage between recurrent and non-recurrent groups (χ2=9.21, P=0.002). The prognostic cutoff values obtained by X-tile software were arterial phase standardized iodine concentration (SIC AP)=0.28 and venous phase standardized iodine concentration (SIC VP)=0.87. The results of log-rank test showed that there were significant differences in RFS among patients with different T-stage, SIC AP and SIC VP (χ2=10.74, 15.50, 17.97, P=0.001,<0.001,<0.001). T-stage, SIC AP and SIC VP were identified as independent predictors of postoperative RFS (hazard ratio=2.271, 3.552, 3.266, P=0.026,<0.001, 0.003). The C-index of the nomogram combined with DECT parameter and T-stage was 0.785, which was higher than that of T-stage alone (0.622). The calibration curve showed that there was good consistency between the actual and predicted probability of the sample. The decision curve analysis showed that the clinical benefit of the nomogram was higher than that of the T-stage alone. Conclusion:The nomogram based on preoperative clinical factors (T-stage) and DECT iodine map factors (SIC AP and SIC vp) can predict the postoperative RFS of patients with EGC.

The predictive value of VEGF, SCCAg and miRNA let-7a in the metastasis and recurrence of laryngeal carcinoma / 中国医师杂志

Objective:To investigate the predictive value of serum vascular endothelial growth factor (VEGF), squamous cell carcinoma-associated antigen (SCCAg) and miRNA let-7a in lymph node metastasis and postoperative recurrence in patients with laryngeal cancer.Methods:A total of 82 patients with laryngeal cancer in the Second Central Hospital of Baoding from November 2017 to October 2019 were selected as the research subjects, including 18 cases of lymph node metastasis (metastasis group) and 64 cases of non metastasis (non metastasis group). The blood routine was tested before operation, and the baseline data, serum VEGF, SCCAg and miRNA let-7a levels were compared between the two groups. Logistic regression was used to analyze the related influencing factors of lymph node metastasis in patients with laryngeal cancer. The correlation between serum VEGF, SCCAg, miRNA let-7a levels and clinicopathological characteristics was analyzed. The receiver operating characteristic (ROC)curve was used to analyze the value of each index and the combined diagnosis of lymph node metastasis in patients with laryngeal cancer. After 1 year of follow-up, the serum VEGF, SCCAg and miRNA let-7a levels of patients with or without recurrent laryngeal cancer were compared. ROC curve was used to evaluate the value of VEGF, SCCAg, and miRNA let-7a in predicting the recurrence of laryngeal cancer.Results:There were statistically significant differences in tumor node metastasis (TNM) stage, degree of infiltration, degree of differentiation, serum VEGF, SCCAg, and miRNA let-7a levels between the metastasis group and non metastasis group (all P<0.05). Serum VEGF, SCCAg, miRNA let-7a levels in patients with laryngeal cancer were related to TNM stage, degree of infiltration and degree of differentiation (all P<0.05). The combined diagnosis of serum VEGF, SCCAg and miRNA let-7a levels in the diagnosis of lymph node metastasis in patients with laryngeal cancer showed that the diagnostic sensitivity and specificity were 88.89% and 70.31%, respectively. The serum VEGF and SCCAg levels of patients with recurrence after operation were higher than those without recurrence, and the level of miRNA let-7a was lower than those without recurrence (all P<0.05). The sensitivity and specificity of combined serum VEGF, SCCAg and miRNA LET-7a levels in predicting postoperative recurrence of laryngeal cancer were 72.97% and 91.11%, respectively. Conclusions:VEGF, SCCAg, miRNA let-7a in patients with laryngeal cancer have a certain correlation with clinicopathological characteristics, which can assist in the diagnosis of lymph node metastasis and help clinical prediction of postoperative recurrence in patients with laryngeal cancer, and provide a reference for the formulation of clinical treatment plans.

Debulking obstructing laryngeal cancers to avoid tracheotomy / Redução de volume tumoral em câncer obstrutivo de laringe para evitar traqueotomia

Abstract Introduction: Upper 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. Objective: To 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. Methods: A 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. Results: In 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. Conclusion: Tumor debulking is a safe and effective method to avoid awake tracheotomy in patients suffering from airway obstruction due to advanced larynx cancer.

Resumo Introdução: A obstrução das vias aéreas superiores com estridor, secundária a neoplasias, é tradicionalmente tratada com traqueotomia. No entanto, este procedimento comum pode potencialmente ter um impacto sobre o desfecho a longo prazo, com a implantação do tumor na ferida cirúrgica da traqueotomia, o que leva à recorrência peristomal após laringectomia, com o risco de recorrência do estoma. Objetivo: Descrever nossa experiência clínica com a redução do volume tumoral como tratamento alternativo à traqueotomia em pacientes com câncer avançado de laringe em um centro de referência terciário. Método: Foi realizada uma revisão retrospectiva de prontuários de 87 indivíduos com câncer avançado de laringe (T3/T4) com obstrução das vias aéreas em nosso banco de dados institucional. Registros médicos incluindo dados demográficos, anotações diárias durante a hospitalização e anotações operacionais foram utilizados como dados clínicos dos pacientes. A estratégia para manter a patência das vias aéreas foi a traqueotomia (emergência ou em pacientes acordados) e redução do volume tumoral (por laser ou coblation). Tumores endofíticos e exofíticos da laringe também foram anotados. Resultados: Uma traqueotomia foi realizada como tratamento inicial em 41/87 (47,1%) pacientes (11 foram de emergência, 30 foram eletivas) para manter a patência das vias aéreas. A redução do volume tumoral foi realizada em 28 lesões exofíticas e 18 endofíticas por laser ou coblation (17 e 29 pacientes, respectivamente). A traqueotomia foi realizada em 5 pacientes (4 endofíticos, 1 exofítico) que não podiam tolerar a cirurgia de redução de volume devido à aspiração, edema e dispneia. Três deles que necessitaram de uma traqueotomia subsequente estavam no grupo de laser e dois no grupo coblation. A taxa de sucesso da redução tumoral foi de 82,35% (14/17) para o laser e 93,1% (27/29) para coblation. Conclusão: A redução do volume tumoral é um método seguro e eficaz para evitar a traqueotomia com paciente acordado, nos casos de obstrução das vias aéreas devido ao câncer de laringe avançado.

Influence of Pathological Differentiation Degree on Neck Dissection of Supraglottic Laryngeal Carcinoma / 肿瘤防治研究

Objective To analyze the patterns of lymph nodes metastasis (LNM) in supraglottic laryngeal squamous cell carcinomas (SLSCC) patients with different tumor differentiation. Methods We retrospectively investigated the clinicopathological data of patients diagnosed as SLSCC. The LNM patterns were analyzed by different tumor differentiation degrees. Results A total of 79 patients were included and divided into poorly differentiated group (n=20), middle differentiated group (n=52) and well differentiated group (n=7). There were 38 patients in N0 stage, 8 patients in N1 stage, 28 patients in N2 stage and 5 patients in N3 stage; 36 patients with LNM in level Ⅱ, 21 patients with LNM in level Ⅲ, 7 patients with LNM in level Ⅳ and no patients with LNM in level Ⅴ or Ⅵ. Conclusion SLSCC patients can benefit from bilateral neck dissection, and the patients with poor or moderate differentiation can benefit from neck dissection (levelsⅡ-Ⅳ), while the patients with well differentiation dissection may be more appropriate for neck dissection (levels Ⅱ-Ⅲ).

Common mental disorders and patient-reported swallowing disorders following total laryngectomy

ABSTRACT Purpose: the aim of this study was to analyze the relationship between patient-reported swallowing disorders and common mental disorders after total laryngectomy. Methods: fourteen patients of both genders and aged 66 ± 8.63 years were assessed after total laryngectomy. They were all asked about the perception of swallowing disorders and answered the Self-Reporting Questionnaire. Patients with swallowing complaints also answered the MD Anderson Dysphagia Inventory. The mean difference between groups was evaluated using the Mann-Whitney test, with a significance level of 5%. Results: the median of Self-Reporting Questionnaire total score was 3.00 [interquartile range: 0.00-5.00] and did not reflect the presence of common mental disorders. Five volunteers (35.7%) self-reported swallowing disorders and had a worse, although not significant (p = 0.15), performance on the Self-Reporting Questionnaire. The MD Anderson Dysphagia Inventory indicated a limitation in the quality of life, with a greater impact of swallowing disorders in the emotional domain [median = 53.30; interquartile range: 33.30-74.95]. Conclusion: common mental disorders are not related to patient-reported swallowing disorders following total laryngectomy. However, patients with swallowing complaints had a negative impact on their quality of life, especially in the emotional domain.

Biomecânica da língua durante a deglutição após laringectomia total: revisão integrativa / Biomechanics of the tongue during swallowing after total laryngectomy: an integrative review

RESUMO Objetivo Sintetizar o estado do conhecimento científico sobre biomecânica da língua durante a deglutição após laringectomia total. Estratégia de pesquisa Formulou-se a questão PICO e combinações de descritores e termos livres para busca nas bases de dados PubMed/Medline, EMBASE, LILACS e SciELO. Critérios de seleção incluíram-se artigos nos idiomas português, inglês ou espanhol; sem limite de tempo; com resultados sobre a biomecânica da língua durante a deglutição em laringectomizados totais; e estudos do tipo ensaio clínico randomizado ou não randomizado, coorte, caso controle, transversal, série de casos e estudos de caso. Análise dos dados analisou-se ano, país, população, objetivo, delineamento do estudo, instrumentos de avaliação, principais desfechos e qualidade metodológica. Resultados Foram incluídos quatro estudos realizados nos Estados Unidos, um na Austrália e um no Brasil, publicados entre 1986 e 2014. Em todos os estudos incluídos a biomecânica da língua foi um desfecho secundário. A maioria dos artigos teve baixa qualidade metodológica, com amostras pequenas, predomínio do sexo masculino e desenho transversal prevalente. Os instrumentos de avaliação foram videofluoroscopia, manometria, acelerômetro ou dispositivo para captar pressão de língua. Resultados principais indicaram mais força de propulsão da base de língua para superar a alta resistência da neofaringe ao fluxo do bolo alimentar; redução do contato e pressão entre base de língua e parede posterior da faringe; resíduo em base de língua após deglutição; pressão aumentada e resistência reduzida da língua oral. Conclusão Existem indícios de movimentos compensatórios de língua durante a deglutição após laringectomia total, porém, as evidências científicas são insuficientes.

ABSTRACT Purpose To synthesize the state of scientific knowledge about biomechanics of the tongue during swallowing after total laryngectomy. Research strategy The PICO question and combinations of descriptors and single terms were formulated in the PubMed/Medline, EMBASE, LILACS, and SciELO databases. Selection criteria Articles in Portuguese, English, or Spanish were included, without time limit, with results on the biomechanics of the tongue during swallowing and total laryngectomy, and studies on randomized or non-randomized clinical trials, cohort, case control, cross-sectional, case series, and case studies. Data analysis year, country, population, objective, study design, assessment methods, main outcomes, and methodological quality were analyzed. Results There were four studies in the United States, one in Australia, and one in Brazil, all published between 1986 and 2014. In all studies, the biomechanics of the tongue was the secondary outcome. Most articles had low methodological quality, small samples, predominance of the male gender, and a prevalent cross-sectional design. The assessment instruments were fluoroscopy, manometry, accelerometer or a device to capture tongue pressure. Main results indicated a higher propulsion force of the tongue base to overcome the high resistance of the neopharynx to the bolus flow, reduced contact and pressure between the base of the tongue and the posterior pharyngeal wall, residues in the tongue base after swallowing, increased pressure, and reduced resistance of the oral tongue. Conclusion There are indications of compensatory tongue movements during swallowing after total laryngectomy; however, the scientific evidence is insufficient.

Incidence and mortality by larynx cancer in Central and South America / Incidencia y mortalidad por cáncer de laringe en Centro y Sudamérica / Incidência e mortalidade por câncer de laringe na América Central e do Sul

ABSTRACT Objective: To describe how the incidence and mortality trends for laryngeal cancer in South and Central American countries. Methods: Time series study, with incidence data from the International Agency for Research on Cancer, from 1990 to 2012 and mortality data from 17 countries of the World Health Organization, from 1995 to 2013. The trend was analyzed by Joinpoint regression. Results: The highest incidence rate for laryngeal cancer was in Brazil, with 5.9 new cases per 100,000 men, and the highest mortality rate in Uruguay with 4.2 deaths per 100,000 men. The incidence ratio between genders ranged from 4: 1 (Colombia) to 12: 1 (Ecuador). The mortality ratio between the sexes ranged from 4: 1 (Peru) to 14: 1 (Uruguay). Conclusion: Most countries had low incidence rates and reduced mortality in Latin America.

RESUMEN Objetivo: Describir cómo tendencias de incidencia y mortalidad por cáncer de laringe en países de América del Sur y Central. Métodos: Estudio de series temporales, con datos de incidencia de Agencia Internacional de Investigación sobre el Cáncer, de 1990 a 2012 y datos de mortalidad de 17 países de Organización Mundial de Salud, de 1995 a 2013. La tendencia se analizó mediante regresión de Joinpoint. Resultados: La tasa de incidencia más alta para el cáncer de laringe fue en Brasil, con 5.9 casos nuevos por cada 100,000 hombres, y tasa de mortalidad más alta en Uruguay con 4.2 muertes por cada 100,000 hombres. La razón de incidencia entre géneros varió de 4: 1 (Colombia) a 12: 1 (Ecuador). La razón de mortalidad entre los sexos varió de 4: 1 (Perú) a 14: 1 (Uruguay). Conclusión: La mayoría de países tenían tasas de incidencia bajas y mortalidad reducida en América Latina.

RESUMO Objetivo: Descrever as tendências da incidência e mortalidade para o câncer de laringe em países da América do sul e central. Métodos: Estudo de série temporal, com dados de incidência da Agência Internacional para Pesquisa do Câncer, no período de 1990-2012 e dados de mortalidade de 17 países da Organização Mundial da Saúde, no período de 1995-2013. A tendência foi analisada pela regressão Joinpoint. Resultados: A taxa de incidência mais elevada para o câncer de laringe foi no Brasil, com 5,9 casos novos por 100.000 homens, e a taxa de mortalidade mais elevada foi no Uruguai com 4,2 óbitos por 100.000 homens. A razão de incidência entre os sexos variou de 4:1 (Colômbia) até 12:1 (Equador). A razão de mortalidade entre os sexos variou de 4:1 (Peru) a 14:1 (Uruguai). Conclusão: A maioria dos países apresentou baixas taxas de incidência e redução de mortalidade na América Latina.

The clinical characteristics and influencing factors on postoperative emotion and cognitive functions for elderly versus non-elderly male patients with laryngeal cancer / 中华老年医学杂志

Objective:To analyze the clinical characteristics and influencing factors on postoperative emotional and cognitive function for elderly versus non-elderly male patients with laryngeal carcinoma.Methods:The patients with laryngeal cancer hospitalized in the Department of Otorhinolaryngology-Head and Neck Surgery were selected for a questionnaire survey in two Grade III-A Hospital in Shanxi Province from January 2018 to December 2019.There were 105 patients with laryngeal cancer, including 60 in the elderly and 45 in the non-elderly group.Negative emotion and cognitive function were investigated by using Self-rating Anxiety Scales(SAS), Self-rating Depression Scale(SDS), and Montreal Cognitive Assessment(MOCA)before surgery, 10 days after surgery, and 1 year after surgery, respectively.The clinical characteristics of the elderly versus non-elderly groups were analyzed and compared.Results:One year after surgery, there were 52 cases(86.7%)and 27 cases(45.0%)of depression and cancer-related cognitive impairment(CRCI)in the elderly group, which were higher than 30 cases(66.7%)and 4 cases(8.9%)in the non-elderly group, with statistically significant difference( χ2 = 6.013, χ2 =16.115 and P<0.05, P<0.01). The elderly group showed much more anxiety and CRCI 10 days after surgery(60.50±4.31 vs.55.84±3.81, 27.47±1.08 vs.28.31±1.08, P<0.01)and showed much more depression and CRCI(57.20±5.66 vs.62.60±5.37, 27.36±1.37 vs.26.08±1.42, P<0.01)than did the non-elderly group 1 year after surgery.The results of multiple linear regression analysis in the elderly group showed that the mode of operation and the pronunciation one year after surgery significantly affected their anxiety; the marriage and the educated level significantly affected their depression; the marriage, the educated level and operation mode significantly affected their cognitive function.Clinical stage of tumor significantly affected anxiety and depression, the educated level significantly affected cognitive function in the non-elderly group. Conclusions:Postoperative negative emotion and cognitive function in patients with laryngeal cancer continues to deteriorate after surgery, which were affected by many factors, especially in elderly patients.It is necessary to conduct active and effective interventions as soon as possible.

The mechanism by which Ginkgo biloba extract induces the apoptosis of human laryngeal cancer Hep-2 cells by reducing reactive oxygen species level and activating JNK signaling pathway / 中国基层医药

Objective:To investigate the apoptosis-inducing effect of Ginkgo biloba extract (Ginaton) on human laryngeal cancer Hep-2 cells and the underlying molecular mechanism.Methods:Human laryngeal cancer Hep-2 cells were cultured in vitro and human laryngeal cancer Hep-2 cells in the log phase were treated with Ginaton in time and concentration gradients. The cell counting kit-8 (CCK-8) assay was performed to investigate the inhibitory effects of Ginaton on Hep-2 cells. Flow cytometry was performed to detect apoptosis and determine the level of reactive oxygen species (ROS). Western blot assay was performed to detect apoptosis and signaling pathway-related protein expression. Results:Ginaton inhibited the proliferation of Hep-2 cells in a time-dependent and concentration-dependent manner. Malondialdehyde level decreased gradually in a time-dependent manner, and decreased to 2.98 μmol/g after 24 hours of Ginaton treatment. Superoxide dismutase level increased gradually in a time-dependent manner and increased to 90.35 U/g after 24 hours of Ginaton treatment. ROS level decreased gradually in a time-dependent manner and deceased to 18.7% of the level before treatment after 24 hours of Ginaton treatment. There was no significant difference in ROS level between before and after 24 hours of Ginaton treatment ( F = 14.98, 19.65, 11.47, all P < 0.001). After 3, 6, 12 and 24 hours of Ginaton treatment, the expression of phosphorylated N-terminal protein kinase increased to 1.98, 2.57, 2.91 and 3.28 in a time-dependent manner. There was significant difference in the expression of phosphorylated N-terminal protein kinase between before treatment and after 3, 6, 12 and 24 hours of Ginaton treatment ( F = 16.37, P < 0.001). Conclusion:Ginaton can effectively inhibit the proliferation and induce apoptosis of human laryngeal cancer Hep-2 cells in vitro, which may be related to regulating ROS level and activating JNK signaling pathway.

An estimate of the incidence and prevalence of laryngeal papillomatosis in São Paulo State (Brasil)

SUMMARY BACKGROUND: Recurrent laryngeal papillomatosis, caused by the Human Papilloma Virus, has a significant economic impact worldwide and there are no epidemiological data of this disease in Brasil. OBJECTIVE: The objective of the study was to estimate the incidence and prevalence of laryngeal papillomatosis of some otorhinolaryngology centers in São Paulo State (Brasil). METHODS: A questionnaire containing data on the number of new and follow-up cases diagnosed with laryngeal papillomatosis was sent to the Otorhinolaryngology services (n=35) of São Paulo State (Brasil). RESULTS: A total of 20 otorhinolaryngology centers answered the questionnaire. Of these, the five largest regional health centers were selected as follows: Campinas (42 cities - 4,536,657 inhabitants), Sao Jose do Rio Preto (102 cities - 1,602,845 inhabitants), Ribeirão Preto (26 cities - 1,483,715 inhabitants), Bauru (68 cities - 1,770,427 inhabitants), and Sorocaba (47 cities - 2,478,208 inhabitants). The incidence and prevalence of each regional health centers were, respectively: Campinas (5.51;7.27), Sorocaba (2.02;6.86), São José do Rio Preto (1.87;7.49), Ribeirão Preto (11.46;22.92), and Bauru (3.95;7.91). CONCLUSION: The incidence and prevalence of the laryngeal papillomatosis of the five largest regional health centers of the interior of São Paulo State (Brasil) varied between 1.87 to 11.46 and 6.86 to 22.92 per 1,000,000 inhabitants, respectively for a total population of 11,871,852 inhabitants.

RESUMO CONTEXTO: A papilomatose recorrente da laringe, causada pelo vírus do papiloma humano, tem um impacto econômico significativo em todo o mundo e não existem dados epidemiológicos dessa doença no Brasil. OBJETIVO: O objetivo do estudo foi estimar a incidência e prevalência de papilomatose laríngea em alguns centros de otorrinolaringologia do estado de São Paulo (Brasil). MÉTODOS: Um questionário contendo dados sobre o número de casos novos e de retornos diagnosticados com papilomatose laríngea foi enviado aos serviços de otorrinolaringologia (n-35) do estado de São Paulo (Brasil). RESULTADOS: Vinte centros de otorrinolaringologia responderam ao questionário e, destes, os cinco maiores centros regionais de saúde foram selecionados da seguinte forma: Campinas (42 cidades - 4.536.657 habitantes), São José do Rio Preto (102 cidades - 1.602.845 habitantes), Ribeirão Preto (26 cidades - 1.483.715 habitantes), Bauru (68 cidades - 1.770.427 habitantes) e Sorocaba (47 cidades - 2.478.208 habitantes). A incidência e prevalência de cada centro de saúde regional foram, respectivamente: Campinas (5,51; 7,27), Sorocaba (2,02; 6,86), São José do Rio Preto (1,87; 7,49), Ribeirão Preto (11,46; 22,92), Bauru (3,95; 7,91). CONCLUSÃO: A incidência e prevalência da papilomatose laríngea dos cinco mais importantes centros regionais de saúde do interior do estado de São Paulo (Brasil) variaram entre 1,87 e 11,46 e 6,86 e 22,92, por 1.000.000 de habitantes, respectivamente, para uma população total de 11.871.852 habitantes.