Nasopharyngeal carcinoma in a non-endemic country-Validation of the new NPC staging system.

BACKGROUND: Nasopharyngeal carcinoma (NPC) staging has recently been updated, with the eighth edition of the AJCC/UICC. In the last ten years, Intensity Modulated Radiotherapy (IMRT) has become a standard treatment for NPC. The authors aim to assess the benefits of the new AJCC staging system in predicting prognosis, as well as the improvement in survival outcomes in the IMRT era, in non-edemic population. METHODS: Retrospective study selecting patients treated for NPC between January 2009 and December 2019 in a cancer treatment center in Portugal. Initial TNM staging (according to the seventh edition of the AJCC/UICC) was collected and each patient was restaged according to the new TNM staging system. Overall survival (OS) and Distant Metastasis Free Survival (DMFS) stratified by T and N classification and stage (according to the both TNM staging systems) were analyzed. Univariate and multivariate analysis was performed to evaluate which factors influence OS and DMFS. Data in this series was compared with a previous report from the same institution, before IMRT standard use. RESULTS: 113 patients were included, averaging 53.74 (±1.4) years old. With the new TNM staging, 5 patients were downstaged and 3 patients were upstaged. Over a median follow-up time of 41 months, the 5-year OS and DMFS were 77% and 79.8%, respectively. Neither the seventh nor the eighth editions of the AJCC/UICC staging system had good overall discrimination between each T classification OS and DMFS curves. Both the seventh and the eighth editions of the AJCC/UICC staging system had statistically significant overall discrimination between each N group and each stage group classification OS curves. Only N classification predicted OS in multivariate analysis. When comparing to a previous report from the same institution, OS has not improved majorly, especially in locoregionally advanced disease. CONCLUSIONS: TNM staging still presents limitations in adequately predicting OS and DMFS.

Nasopharyngeal carcinoma in a non-endemic country—Validation of the new NPC staging system

Background: Nasopharyngeal carcinoma (NPC) staging has recently been updated, with the eighth edition of the AJCC/UICC. In the last ten years, Intensity Modulated Radiotherapy (IMRT) has become a standard treatment for NPC. The authors aim to assess the benefits of the new AJCC staging system in predicting prognosis, as well as the improvement in survival outcomes in the IMRT era, in non-edemic population.MethodsRetrospective study selecting patients treated for NPC between January 2009 and December 2019 in a cancer treatment center in Portugal. Initial TNM staging (according to the seventh edition of the AJCC/UICC) was collected and each patient was restaged according to the new TNM staging system. Overall survival (OS) and Distant Metastasis Free Survival (DMFS) stratified by T and N classification and stage (according to the both TNM staging systems) were analyzed. Univariate and multivariate analysis was performed to evaluate which factors influence OS and DMFS. Data in this series was compared with a previous report from the same institution, before IMRT standard use.Results113 patients were included, averaging 53.74 (±1.4) years old. With the new TNM staging, 5 patients were downstaged and 3 patients were upstaged. Over a median follow-up time of 41 months, the 5-year OS and DMFS were 77% and 79.8%, respectively. Neither the seventh nor the eighth editions of the AJCC/UICC staging system had good overall discrimination between each T classification OS and DMFS curves. Both the seventh and the eighth editions of the AJCC/UICC staging system had statistically significant overall discrimination between each N group and each stage group classification OS curves. Only N classification predicted OS in multivariate analysis. When comparing to a previous report from the same institution, OS has not improved majorly, especially in locoregionally advanced disease.ConclusionsTNM staging still presents limitations in adequately predicting OS and DMFS. (AU)

Antecedentes: La estadificación del carcinoma nasofaríngeo (NPC, por sus siglas en inglés) se ha actualizado recientemente, con la octava edición del AJCC/UICC. En los últimos 10 años, la radioterapia de intensidad modulada (IMRT, por sus siglas en inglés) se ha convertido en un tratamiento estándar para la NPC. Los autores pretenden evaluar los beneficios del nuevo sistema de estadificación del AJCC en la predicción del pronóstico, así como la mejora en los resultados de supervivencia en la era de la IMRT, en una población non endémica.MétodosEstudio retrospectivo de selección de pacientes tratados por NPC entre enero de 2009 y diciembre de 2019 en un centro de tratamiento del cáncer en Portugal. Se recopiló la estadificación TNM inicial (según la séptima edición del AJCC/UICC) y se reestadificó cada paciente de acuerdo con el nuevo sistema de estadificación TNM. Se analizaron la supervivencia global (SG) y la supervivencia libre de metástasis a distancia (SLMD) estratificadas por clasificación T y N y estadio (según ambos sistemas de estadificación TNM). Se realizó un análisis univariante y multivariante para evaluar qué factores influyen en la SG y la SLMD. Los datos de esta serie se compararon con un informe anterior de la misma institución, antes del uso estándar de la IMRT.ResultadosSe incluyeron 113 pacientes, con una edad promedio de 53,74 (±1,4) años. Con la nueva estadificación TNM, 5 pacientes aumentaron estadio y 3 pacientes disminuyeron estadio. Durante una mediana de tiempo de seguimiento de 41 meses, la SG y la SLMD a 5 años fueron del 77 y del 79,8%, respectivamente. (AU)

Surgically-Treated Locoregionally Advanced Hypopharyngeal Cancer: Outcomes

Abstract Introduction Hypopharyngeal tumors are head and neck malignancies associated with a great mortality rate, and the treatment of advanced lesions constitutes a challenging problem. Pharyngolaryngectomy continues to be the gold standard treatment modality for locally-advanced diseases, and it is currently used as the primary treatment or in cases of relapse after an organ preservation strategy. Objective This study aims to compare the survival rates of patients with advanced hypopharyngeal tumors treated with pharyngolaryngectomy as a primary or salvage option, and identify possible prognostic factors. Methods All patients with advanced hypopharyngeal squamous cell carcinomas who performed pharyngolaryngectomy between 2007 and 2014 were reviewed retrospectively. Results A total of 87 patients fulfilled the aforementioned criteria, and the sample had a mean age of 57.2 years and a male predominance of 43:1. The tumors were located in the pyriform sinus walls (81 tumors), in the posterior pharyngeal wall (4 tumors) and in the postcricoid region (2 tumors). A total of 60 patients underwent surgery as the primary treatment option, and 27 were submitted to salvage pharyngolaryngectomy after a previous treatment with chemoradiotherapy or radiotherapy. The 5-year overall survival was of 25.9%, the 5-year disease-free survival was of 24.2%, and the disease-specific survival was of 29.5%. Conclusion The patients treated with pharyngolaryngectomy as the primary option revealed a better 5-year-disease free survival than the patients who underwent the salvage surgery (35.8% versus 11.7% respectively; p< 0.05). The histopathological criteria of capsular rupture of the lymph nodes (30.1% versus 19.8% respectively for the primary and salvage groups; p< 0.05) and vascular invasion (30.5% versus 22.5% respectively; p< 0.05) reduced the 5-year disease-free survival. Pharyngolaryngectomy as the primary intent revealed a lower local recurrence rate than the salvage surgery (40.6% versus 83.3% respectively; p< 0.05).

Surgically-Treated Locoregionally Advanced Hypopharyngeal Cancer: Outcomes.

Introduction Hypopharyngeal tumors are head and neck malignancies associated with a great mortality rate, and the treatment of advanced lesions constitutes a challenging problem. Pharyngolaryngectomy continues to be the gold standard treatment modality for locally-advanced diseases, and it is currently used as the primary treatment or in cases of relapse after an organ preservation strategy. Objective This study aims to compare the survival rates of patients with advanced hypopharyngeal tumors treated with pharyngolaryngectomy as a primary or salvage option, and identify possible prognostic factors. Methods All patients with advanced hypopharyngeal squamous cell carcinomas who performed pharyngolaryngectomy between 2007 and 2014 were reviewed retrospectively. Results A total of 87 patients fulfilled the aforementioned criteria, and the sample had a mean age of 57.2 years and a male predominance of 43:1. The tumors were located in the pyriform sinus walls (81 tumors), in the posterior pharyngeal wall (4 tumors) and in the postcricoid region (2 tumors). A total of 60 patients underwent surgery as the primary treatment option, and 27 were submitted to salvage pharyngolaryngectomy after a previous treatment with chemoradiotherapy or radiotherapy. The 5-year overall survival was of 25.9%, the 5-year disease-free survival was of 24.2%, and the disease-specific survival was of 29.5%. Conclusion The patients treated with pharyngolaryngectomy as the primary option revealed a better 5-year-disease free survival than the patients who underwent the salvage surgery (35.8% versus 11.7% respectively; p < 0.05). The histopathological criteria of capsular rupture of the lymph nodes (30.1% versus 19.8% respectively for the primary and salvage groups; p < 0.05) and vascular invasion (30.5% versus 22.5% respectively; p < 0.05) reduced the 5-year disease-free survival. Pharyngolaryngectomy as the primary intent revealed a lower local recurrence rate than the salvage surgery (40.6% versus 83.3% respectively; p < 0.05).

Discrepancy between clinical and pathological neck staging in oral cavity carcinomas / Discrepancia entre el estadiaje clínico y patológico cervical en los carcinomas de cavidad oral

Introduction: The presence of cervical lymph node metastases in patients with oral cavity squamous cell carcinoma reduces survival by up to 50%. Objective: The aims of this study are to assess the accuracy of clinical N staging versus pathological N staging and its impact on survival in order to identify predictive factors associated with the presence of occult neck metastases. Methods: Outcomes of 105 patients with oral cavity squamous cell carcinoma who underwent surgical treatment of the primary tumor and neck were retrospectively evaluated. Results: For pN0 and pN+ patients 5-year overall survival was respectively 53% and 27%; disease specific survival was 66% for pN0 and 33% for pN+. Patients with clinical negative lymph nodes were pathologically upstaged in 62% of cases. Disease specific survival according to staging discrepancy had statistically significant impact on survival (p = 0.009). Conclusion: Clinical staging usually underestimates the presence of nodal disease. Neck dissection should be performed in cN0 oral cavity squamous cell carcinoma (AU)

Introducción: La presencia de metástasis ganglionares cervicales en los pacientes con carcinoma de la cavidad oral reduce la supervivencia hasta en un 50%. Objetivos: Los objetivos de este estudio son evaluar la exactitud del estadiaje N clínico frente al estadiaje N patológico y su impacto en la supervivencia, de cara a identificar los factores predictivos asociados a la presencia de metástasis ocultas cervicales. Métodos: Se han evaluado retrospectivamente los resultados de 105 pacientes con carcinoma epidermoide de la cavidad oral tras tratamiento quirúrgico del tumor primario y vaciamiento cervical. Resultados: En los pacientes pN0 y pN+ la supervivencia global a los 5 años fue del 53 y del 27%, respectivamente, y la supervivencia específica libre de enfermedad fue del 66% para los pN0 y del 33% para los pN+. En los pacientes estadiados clínicamente como negativos se verificó un subestadiaje en el 62% de los casos. La supervivencia específica libre de enfermedad en función de la discrepancia del estadiaje tuvo un impacto estadísticamente significativo en la supervivencia (p = 0,009). Conclusión: El estadiaje clínico suele subestimar la presencia de enfermedad ganglionar. La disección cervical debe realizarse en los carcinomas de cavidad oral aunque se trate de uno cN0 (AU)

Transoral laser microsurgery as standard approach to hypopharyngeal cancer. Survival analysis in a hospital based population / Microcirugía transoral láser con CO2 como una opción válida para el tratamiento del cáncer de hipofaringe en un hospital terciario

Objective: Cancer of the hypopharynx remains one of the most challenging chapters in head and neck oncology. The objective of this study is to ascertain the relevance of a transoral laser approach as a valid functional option for treatment of cancer of the hypopharynx in Portugal, and additionally, to confirm the reproducibility of survival and functional outcomes described in other reference centers. Subjects and methods: The outcomes of 37 out of 60 patients presenting hypopharyngeal carcinoma primarily treated by TLM (transoral laser microsurgery) and neck dissection and or adjuvant treatment when needed, with curative intention in tertiary referral center, were retrospectively evaluated and compared with published results. Results: There were no patients in stage I. Three-year and five-year overall survival (Kaplan-Meier) were 83.5% and 63.5% for stage II (n = 12), 57.1% (only 3-year overall survival evaluable for this stage) for stage III (n = 7), and 53.1% and 39.8% for stage IVa (n = 18), respectively. Five-year local control rates were 90% for stage II and 87.5% for stage IVa, respectively; only three-year local control rates were possible to evaluate for stage III, with a 100% control rate. Five-year total larynx preservation rate was 97.3%. Conclusions: TLM, alone or with neck dissection and adjuvant therapy, is a valid procedure for treatment of hypopharyngeal cancer in different stages. Furthermore, this kind of approach can be replicated in different oncologic centers with similar oncologic and functional results (AU)

Objetivo: El cáncer de hipofaringe continúa siendo uno de los capítulos más difíciles en la oncología de cabeza y cuello. El objetivo del presente estudio es determinar la relevancia del abordaje con microcirugía transoral láser CO2 (MTL) como una opción válida para el tratamiento de cáncer de hipofaringe en un hospital terciario. Adicionalmente, se pretende comparar los datos obtenidos con los de otros centros de referencia en relación a la supervivencia y a los resultados funcionales. Pacientes y Métodos: 37 pacientes de un total de 60 con diagnóstico de carcinoma hipofaríngeo han sido tratados con intención curativa con MTL sola o asociada á disección cervical y terapia adyuvante. Los resultados han sido evaluados retrospectivamente y comparados con los publicados en la literatura. Resultados: No hubo pacientes en estadio I. La supervivencia global a los 3 y 5 años (Kaplan-Meir) fue de 83.5% y 63.5% en el estadio II (n=12); 57.1% en el estadio III (n=7) (en este estadio sólo pudo ser evaluada la supervivencia global a los 3 años) y 53.1% y 39.8% para el estadio IVa (n=18) respectivamente. El porcentaje de control local a los 5 años fue de 90% en el estadio II y de 87.5% en el estadio IVa, respectivamente; en el estadio III, solamente ha sido posible evaluar el control local a los 3 años, que ha sido de 100%. El porcentaje total de preservación laríngea a los 5 años fue de 97.3%. Conclusiones: La MLT, sola o asociada a la disección cervical y terapia adyuvante, es un procedimiento eficiente para el tratamiento del cáncer hipofaringeo en diferentes estadios. Esto confirma que este abordaje es una opción válida y reproducible en diferentes centros oncológicos (AU)

Transoral laser microsurgery as standard approach to hypopharyngeal cancer. Survival analysis in a hospital based population.

OBJECTIVE: Cancer of the hypopharynx remains one of the most challenging chapters in head and neck oncology. The objective of this study is to ascertain the relevance of a transoral laser approach as a valid functional option for treatment of cancer of the hypopharynx in Portugal, and additionally, to confirm the reproducibility of survival and functional outcomes described in other reference centers. SUBJECTS AND METHODS: The outcomes of 37 out of 60 patients presenting hypopharyngeal carcinoma primarily treated by TLM (transoral laser microsurgery) and neck dissection and or adjuvant treatment when needed, with curative intention in tertiary referral center, were retrospectively evaluated and compared with published results. RESULTS: There were no patients in stage I. Three-year and five-year overall survival (Kaplan-Meier) were 83.5% and 63.5% for stage II (n=12), 57.1% (only 3-year overall survival evaluable for this stage) for stage III (n=7), and 53.1% and 39.8% for stage IVa (n=18), respectively. Five-year local control rates were 90% for stage II and 87.5% for stage IVa, respectively; only three-year local control rates were possible to evaluate for stage III, with a 100% control rate. Five-year total larynx preservation rate was 97.3%. CONCLUSIONS: TLM, alone or with neck dissection and adjuvant therapy, is a valid procedure for treatment of hypopharyngeal cancer in different stages. Furthermore, this kind of approach can be replicated in different oncologic centers with similar oncologic and functional results.

Discrepancy between clinical and pathological neck staging in oral cavity carcinomas.

INTRODUCTION: The presence of cervical lymph node metastases in patients with oral cavity squamous cell carcinoma reduces survival by up to 50%. OBJECTIVE: The aims of this study are to assess the accuracy of clinical N staging versus pathological N staging and its impact on survival in order to identify predictive factors associated with the presence of occult neck metastases. METHODS: Outcomes of 105 patients with oral cavity squamous cell carcinoma who underwent surgical treatment of the primary tumor and neck were retrospectively evaluated. RESULTS: For pN0 and pN+ patients 5-year overall survival was respectively 53% and 27%; disease specific survival was 66% for pN0 and 33% for pN+. Patients with clinical negative lymph nodes were pathologically upstaged in 62% of cases. Disease specific survival according to staging discrepancy had statistically significant impact on survival (p=0.009). CONCLUSION: Clinical staging usually underestimates the presence of nodal disease. Neck dissection should be performed in cN0 oral cavity squamous cell carcinoma.

Malignant tumors of the temporal bone - our experience / Tumores malignos do osso temporal - a nossa experiência

ABSTRACT INTRODUCTION: Malignant tumors of the temporal bone are rare, with an estimated incidence of about 0.8-1.0 per 1,000,000 inhabitants per year. The vast majority of these tumors are squamous cell carcinomas and their treatment is eminently surgical. OBJECTIVE: This study is an attempt at systematizing the forms of clinical presentation, the therapeutic possibilities, and oncological outcomes of patients with malignant tumors of the temporal bone in a tertiary hospital in Portugal. METHODS: The authors present a retrospective study of temporal bone tumors treated and followed during otorhinolaryngology consultations between 2004 and 2014. A review of the literature is also included. RESULTS: Of the 18 patients included in the study, 16 had a primary tumor of the temporal bone, in most cases with squamous cell carcinoma histology. Of these, 13 patients were treated with curative intent that always included the surgical approach. Disease persistence was observed in one patient and local recurrence in five patients, on average 36.8 months after the initial treatment. CONCLUSIONS: The anatomical complexity of the temporal bone and the close associations with vital structures make it difficult to perform tumor resection with margins of safety and thus, tumor relapses are almost always local. A high level of suspicion is crucial for early diagnosis, and stringent and prolonged follow-up after treatment is essential for diagnosis and timely treatment of recurrances.

Resumo Introdução: Os tumores malignos do osso temporal são raros, com uma incidência estimada de cerca de 0,8-1 por milhão de habitantes por ano. A grande maioria são carcinomas espinocelulares e o seu tratamento é eminentemente cirúrgico. Objetivo: Este trabalho tem como objetivo tentar sistematizar as formas de apresentação clínica, as possibilidades terapêuticas e os resultados oncológicos de doentes com tumores malignos do osso temporal num hospital terciário em Portugal. Método: Os autores apresentam um estudo retrospectivo de tumores do osso temporal tratados e acompanhados em consultas de otorrinolaringologia entre 2004 e 2014. É também apresentada uma revisão da literatura. Resultados: Dos 18 doentes incluídos no estudo, 16 apresentavam um tumor primário do osso temporal, na maioria dos casos com histologia de carcinoma espinocelular. Destes, 13 doentes foram submetidos a tratamento com intuito curativo que incluiu sempre uma abordagem cirúrgica. Verificou-se persistência da doença em 1 doente e recidiva local em 5 doentes, em média 36,8 meses após o tratamento inicial. Conclusões: A complexidade anatómica do osso temporal e as estreitas relações com estruturas de importância vital tornam difícil a exérese tumoral com margens de segurança, pelo que as recidivas tumorais são quase sempre locais. Um nível de suspeição elevado é fundamental para um diagnóstico precoce e o seguimento rigoroso e prolongado após o tratamento é essencial para o diagnóstico e tratamento oportuno das recidivas.

Malignant tumors of the temporal bone - our experience.

INTRODUCTION: Malignant tumors of the temporal bone are rare, with an estimated incidence of about 0.8-1.0 per 1,000,000 inhabitants per year. The vast majority of these tumors are squamous cell carcinomas and their treatment is eminently surgical. OBJECTIVE: This study is an attempt at systematizing the forms of clinical presentation, the therapeutic possibilities, and oncological outcomes of patients with malignant tumors of the temporal bone in a tertiary hospital in Portugal. METHODS: The authors present a retrospective study of temporal bone tumors treated and followed during otorhinolaryngology consultations between 2004 and 2014. A review of the literature is also included. RESULTS: Of the 18 patients included in the study, 16 had a primary tumor of the temporal bone, in most cases with squamous cell carcinoma histology. Of these, 13 patients were treated with curative intent that always included the surgical approach. Disease persistence was observed in one patient and local recurrence in five patients, on average 36.8 months after the initial treatment. CONCLUSIONS: The anatomical complexity of the temporal bone and the close associations with vital structures make it difficult to perform tumor resection with margins of safety and thus, tumor relapses are almost always local. A high level of suspicion is crucial for early diagnosis, and stringent and prolonged follow-up after treatment is essential for diagnosis and timely treatment of recurrances.

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal.

BACKGROUND: Host genetic susceptibility markers in immune response associated genes may contribute to identify individuals with high risk of developing viral infection and viral-associated cancers. We aimed to characterize different polymorphisms in immune response associated genes and evaluate its association with nasopharyngeal carcinoma (NPC) development. METHODS: We have developed a hospital-based case-control study selecting 134 patients with NPC (cases) and 732 healthy individuals (controls) from the Northern Region of Portugal. Eight single nucleotide polymorphisms (SNP) were selected: -56C>T IFNGR1 (rs2234711), +4854G>T IL1A (rs17561), +3954C>T IL1B (rs1143634), +1902A>G IL4RA (rs1801275), -1082G>A IL10 (rs1800896), +2018T>C IL1RN (rs419598), HLA-A locus A>T (rs2530388), HCGA9 locus A>T (rs6457110). All polymorphisms were analysed by real-time methodology using TaqMan(®) SNP Genotyping Assays. RESULTS: The overall analysis revealed no statistical significant differences between genotypes distributions in all of studied polymorphisms (p>0.05). However, the results for HCGA9 rs6457110 polymorphism showed a tendency for an increased risk of NPC development among TT carriers with an almost of 2-fold increased risk (OR=1.86; 95%CI 1.00-3.65). CONCLUSIONS: This is the first study to characterize these polymorphisms in NPC patients in Portugal. Our study indicates that HCGA9 rs6457110 polymorphism might represent a risk marker for NPC development in our population and that other SNPs should be further studied in larger populations to clarify the evidences. This data reinforces the need for more studies, especially in NPC low-prevalent populations.

Characterization of Epstein-Barr virus strains and LMP1-deletion variants in Portugal.

Variations in the genome sequence of Epstein-Barr Virus (EBV) are thought to lead to differential interaction with host cells, immune evasion, and transformation. The discussion regarding EBV strains as having a geographic or disease-association has been increasing and the majority of studies are performed in Asiatic populations. We developed a case-control study with 139 individuals, including 96 subjects with different malignancies and 43 healthy individuals, from the North region of Portugal. We have used PCR protocols for the characterization of EBV strains (type A or B) based on EBNA3C genome variation and for the LMP1 30bp-deletion variants (wt-LMP1 or del-LMP1). Our study showed that type A is the most prevalent in our population (100% of healthy controls, 96.9% of aHSCT patients, 90.8% of HNSCC patients, and 94.9% of NPC patients) and that type B was significantly associated with NPC (P = 0.019; RR = 8.90). Regarding the LMP1 30bp-deletion, we found a similar distribution of both wt- and del-LMP1 variants in controls and dispare results in cases: del-LMP1 was more frequent in aHSCT and HNSCC patients (64.7% and 63.2%, respectively) and wt-LMP1 in NPC patients (100%). In fact, the study reveals that wt-LPM1 was significantly associated with NPC (P < 0.001; RR = 18.4). Hence, our study showed that EBV type B and wt-LMP1 variant seem to be associated with NPC in our population, with a clear disease-association for wt-LMP1. These results contribute for the knowledge of EBV genetic diversity among Caucasian populations.

Transoral laser microsurgery for laryngeal carcinoma: Survival analysis in a hospital-based population.

BACKGROUND: Although already established for treatment for early-stage laryngeal cancers, transoral laser microsurgery indications for more advanced tumors are not unanimous. Additionally, no outcomes concerning the Portuguese population are currently accessible. METHODS: Outcomes of 248 patients presenting laryngeal carcinoma primarily treated by transoral laser microsurgery with curative intention in tertiary referral center were retrospectively evaluated and compared with concerning literature. RESULTS: For supraglottic tumors (23 stage I-II and 20 stage III-IV), 5-year disease-specific survival (DSS) was, respectively, 88.4% and 72.7%, and the total larynx-preservation rate was 90.7%. For glottic cancer (165 stage I-II and 40 stage III-IV), 5-year DSS was, respectively, 96.5% and 90.8% and the larynx preservation rate was 88.3%. CONCLUSION: Transoral laser microsurgery, alone or with neck dissection and adjuvant therapy, is an efficient procedure for treatment of laryngeal cancer in different stages. To the best of our knowledge, this is the first study reporting transoral laser microsurgery outcomes in the Portuguese population.

IL-1RN VNTR polymorphism as a susceptibility marker for nasopharyngeal carcinoma in Portugal.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare malignancy in Western countries that is widely associated with the infection by Epstein-Barr virus (EBV). Several studies have showed that a common allele (allele 2) of the 86-bp variable number of tandem repeats (VNTR) polymorphism within intron 2 of the interleukin 1 receptor antagonist (IL-1RN) gene is associated with several disorders, including viral-associated cancers. METHODS: We have developed a hospital-based case-control study to characterise the role of the IL-1RN 86-bp VNTR polymorphism in the development of NPC with 112 patients with the disease and 433 healthy individuals from the northern region of Portugal. IL-1RN genotypes were combined according to the number of repeats: allele 2 (A2), the short allele that corresponds to two repeats, and L, the long allele that corresponds to three or more repeats. RESULTS: Our study revealed that 31.2% of NPC patients were IL-1RN A2*A2, compared with 9.7% observed in the control group. The statistical analysis revealed that IL-1RN*A2 homozygosity for the A2 allele was associated with a fourfold increased risk for NPC development (p<0.001). Additionally, cumulative hazard analysis revealed that estimated median age of onset of NPC is significantly (p<0.001) different for A2*A2 homozygous versus non-A2*A2 (57.0 vs. 74.0, respectively). CONCLUSIONS: This is the first study to evaluate the role of the IL-1RN VNTR in NPC development in Portugal. Our study indicates IL-1RN*A2 homozygosity as a significant risk marker in our population and that it should be further investigated for the potential role in the definition of a susceptibility profile for NPC onset.

Significado pronóstico de las metástasis cervicales en tumores avanzados de laringe e hipofaringe / Prognostic significance of nodal metastasis in advanced tumors of the larynx and hypopharynx

Objetivos: Valorar la relevancia de la estadificación pN posquirúgica de los ganglios cervicales en la supervivencia global de los pacientes con tumores avanzados de laringe e hipofaringe, primariamente tratados con cirugía, incluyendo disección cervical (DC). Entender el significado pronóstico de la extensión extracapsular (EEC) de los ganglios linfáticos metastásicos y su impacto en la supervivencia. Material y métodos: Se realizó un estudio retrospectivo de pacientes primariamente sometidos a una laringectomía total (LT) con DC bilateral electiva o terapéutica. Se analizaron las supervivencias global y libre de la enfermedad, de acuerdo con los resultados histopatológicos posquirúrgicos de la DC, concernientes a la presencia o no de la afectación ganglionar, número de ganglios afectados, y existencia de EEC. Resultados: Ciento veinte pacientes cumplieron los criterios de inclusión del presente estudio. En cuanto a la afectación ganglionar, la evaluación histopatológica demostró positividad en el 46,6% de los pacientes cN0.La tasa de pacientes vivos a los 2 años de seguimiento, basada en el análisis pN, fue del 88,1% para el grupo pN0, del 65,4% para el grupo N+ sin EEC, del 46,2% para el grupo N+ con EEC en un ganglio, y del 15,4% para el grupo N+ con EEC en más de un ganglio (p<0,001). Conclusiones: Este estudio demuestra una alta prevalencia de la enfermedad oculta en el cuello, en tumores de laringe e hipofaringe. La afectación metastásica de ganglios linfáticos tiene un impacto negativo en la supervivencia. Los pacientes con EEC multinodal tienen una peor supervivencia, lo cual se reflejó en una mayor tasa de metástasis locorregionales y a distancia, en comparación a los casos de EEC que afecta a un único ganglio linfático(AU)

Objectives: To estimate the relevance of post-surgical neck nodal classification (pN) on the global survival of patients with advanced tumors of the larynx and hypopharynx, primarily treated with surgery including neck dissection (ND). To understand the prognostic significance of metastatic lymph nodes’ extracapsular spread (ECS) and its impact on survival. Material and methods: A retrospective review of patients primarily submitted for total laryngectomy (TL) with either elective or therapeutic bilateral ND. Overall and disease-free survival was analysed according to post-operative histopathological ND results, concerning the presence or absence of nodal involvement, number of affected nodes and the existence of ECS. Results: One hundred and twenty patients met the inclusion criteria of this study. Concerning nodal involvement, the histopathological evaluation demonstrated positive lymph nodes in 46.6% of the cN0 patients. The rate of patients alive after 2 years of follow-up, based on pN analysis, was 88.1% for the pN0 group, 65.4% for the group N+ without ECS, 46.2% for the N+ ECS+ (1 node) and 15.4% for the N+ ECS+ (more than 1 node) group (P<0.001). Conclusions: This study demonstrates a high prevalence of occult neck disease in tumours of the larynx and hypopharynx. The involvement of metastatic cervical lymph nodes has a negative impact on survival. Patients with multinodal ECS have a poorer survival, reflected by a higher rate of loco-regional and distant metastases, when compared to ECS in one single lymph node(AU)

Prognostic significance of nodal metastasis in advanced tumors of the larynx and hypopharynx.

OBJECTIVES: To estimate the relevance of post-surgical neck nodal classification (pN) on the global survival of patients with advanced tumors of the larynx and hypopharynx, primarily treated with surgery including neck dissection (ND). To understand the prognostic significance of metastatic lymph nodes' extracapsular spread (ECS) and its impact on survival. MATERIAL AND METHODS: A retrospective review of patients primarily submitted for total laryngectomy (TL) with either elective or therapeutic bilateral ND. Overall and disease-free survival was analysed according to post-operative histopathological ND results, concerning the presence or absence of nodal involvement, number of affected nodes and the existence of ECS. RESULTS: One hundred and twenty patients met the inclusion criteria of this study. Concerning nodal involvement, the histopathological evaluation demonstrated positive lymph nodes in 46.6% of the cN0 patients. The rate of patients alive after 2 years of follow-up, based on pN analysis, was 88.1% for the pN0 group, 65.4% for the group N+ without ECS, 46.2% for the N+ ECS+ (1 node) and 15.4% for the N+ ECS+ (more than 1 node) group (P<.001). CONCLUSIONS: This study demonstrates a high prevalence of occult neck disease in tumours of the larynx and hypopharynx. The involvement of metastatic cervical lymph nodes has a negative impact on survival. Patients with multinodal ECS have a poorer survival, reflected by a higher rate of loco-regional and distant metastases, when compared to ECS in one single lymph node.

Rhizomucor and scedosporium infection post hematopoietic stem-cell transplant.

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

Role of the MDM2 SNP309 polymorphism in the initiation and early age of onset of nasopharyngeal carcinoma.

Recent studies refer that amplification/overexpression of the principal negative regulator of p53 (Mdm2) is frequently found in several malignancies. Several studies have associated a polymorphism (SNP309 T/G) in the promoter region of MDM2 with higher levels of this protein, which will favor p53-pathway abolishment, cell-cycle escape, and development of cancer. We aimed to study if MDM2 SNP309 T/G polymorphism contributes to the development of nasopharyngeal carcinoma (NPC). We have developed a case-control study with 124 patients with NPC and 509 healthy individuals from the north of Portugal to determine the genetic distribution of the MDM2 SNP309 polymorphism in DNA extracted from peripheral blood samples. Statistical analysis was performed to compare categorical variables adjusted for age and gender by multivariate logistic regression. Genotype-specific distributions according to age of onset were tested by Kaplan-Meier method and analyzed by Cox-regression proportional hazard model adjusted for gender. This study revealed that MDM2 SNP309 GG homozygous represent an increased risk adjusted for age and gender to develop NPC (OR = 2.15), with particular effect in undifferentiated types (OR = 2.46) and early clinical stages (OR = 3.32). We also found that median age of onset of NPC was significantly different (55.2 vs. 61.6) with increased effect in undifferentiated types (55.2 vs. 61.9) and early clinical stages (55.3 vs. 65.3). Our study suggests that MDM2 SNP309 can be considered a risk marker for the development of NPC mainly in early ages probably as an initiation marker for potential cancer development.

Genetic risk markers for nasopharyngeal carcinoma in Portugal: tumor necrosis factor alpha -308G >A polymorphism.

The tumor necrosis factor-alpha (TNF-α) is a strong proinflammatory cytokine produced by the activated macrophages in the immune response to viral infections. A common polymorphism on the promoter region of TNFA gene (-308G >A) has been associated with different susceptibilities to the development of several diseases including viral-associated neoplasias. Data suggest that the A allele has been associated with higher levels of TNF-α and, therefore, leads to increased risk of cancer development. We have performed a case-control study considering the role of the -308G >A polymorphism in 750 individuals from the northern region of Portugal, including 123 patients with nasopharyngeal carcinoma (NPC) and 627 healthy individuals. Our study revealed an increased frequency of the -308A TNFA allele in patients with NPC. The statistical analysis for recessive model revealed that -308AA genotype is associated with increased risk for the development of NPC (odds ratio = 2.46; 95% confidence interval, 0.98-6.17; p = 0.047); moreover, this effect was stronger in undifferentiated types, which are virtually 100% caused by the Epstein-Barr virus (odds ratio = 2.75; 95% confidence interval, 1.09-6.90; p = 0.025). These results reveal that in our population -308 TNFA AA genotype can represent a risk marker for NPC development and contributes for the definition of genetic susceptibility profiles for individuals at risk of development of a viral infection and associated neoplasia.

Epstein-Barr virus detection in nasopharyngeal carcinoma: implications in a low-risk area.

UNLABELLED: Several studies have been published concerning Epstein-barr virus (EBV) infection and nasopharyngeal cancer (NPC) development. The incidences of histological types are different according to endemic or non-endemic regions. Latent EBV infection is found in almost all cases of NPC in endemic regions, but normally absent in type I carcinomas, more common in non-endemic regions. AIM: The purpose of this hospital-based study was to analyze the presence of EBV in nasopharyngeal tumor tissues and in peripheral blood of nasopharyngeal cancer patients and healthy individuals, in a low risk, non-endemic area. METHODS: EBV detection in samples of nasopharyngeal cancer patients and healthy individuals. RESULTS: This study indicates that the frequency of EBV positive cases in peripheral blood is higher in advanced tumor stages. CONCLUSIONS: The incidence rates of NPC have a distinct distribution. Since the prevalence of this disease is low in occidental countries, little is known about the biology of these tumors in non-endemic areas. We observed statistically significant differences in EBV detection between the NPC patient group and the control group. This study may help to understand the biological mechanisms of NPC and the correlation of EBV infection with this disease, in a low risk, non-endemic region.