Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Prognostic factors in metastatic nasopharyngeal carcinoma / Fatores prognósticos no carcinoma nasofaríngeo metastático

Abstract Introduction: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. Objective: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. Results: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3-G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. Conclusion: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo tem o maior potencial metastático de todos os tipos de câncer de cabeça e pescoço. O tempo de sobrevida dos pacientes com carcinoma nasofaríngeo melhorou significativamente nas últimas décadas devido ao uso combinado de quimioterapia e radioterapia e os avanços nas técnicas de radioterapia. No entanto, aproximadamente 30% dos pacientes com carcinoma nasofaríngeo têm um prognóstico ruim, principalmente devido a metástases a distância. Objetivo: Identificar a sobrevida e os fatores prognósticos no carcinoma nasofaríngeo metastático. Método: Foi feita uma análise retrospectiva de pacientes tratados por carcinoma nasofaríngeo metastático sincrônico ou carcinoma nasofaríngeo metastático metacrônico por 14 anos (2003-2016). A sobrevida global foi analisada pelo método de Kaplan-Meier e comparada pelo teste de log-rank para toda a população e ambos os grupos de pacientes. A análise multivariada foi feita com o modelo de Cox; valores de p < 0,05 foram considerados como significância estatística. Resultados: Foram incluídos 112 pacientes com carcinoma nasofaríngeo metastático (51 com carcinoma nasofaríngeo metastático sincrônico e 61 com carcinoma nasofaríngeo metastático metacrônico). Em toda a população, a mediana da sobrevida global foi de 10 meses (1-156 meses). Na análise multivariada, sexo feminino, baixo status de desempenho (OMS > 1) e metástase metacrônica foram fatores prognósticos independentes. Nos pacientes com carcinoma nasofaríngeo metastático sincrônico, a mediana da sobrevida global foi de 13 meses (1-156 meses). Na análise multivariada, os fatores prognósticos independentes foram doença não oli-gometastática, toxicidade grave à quimioterapia (G3 - G4) e falta de irradiação nasofaríngea e do sítio metastático. Nos pacientes com carcinoma nasofaríngeo metastático metacrônico, a mediana da sobrevida global foi de 7 meses (1-41 meses). Na análise multivariada, o baixo status de desempenho (OMS > 1) foi um fator prognóstico independente. Conclusão: Pacientes oligometastáticos com carcinoma nasofaríngeo metastático sincrônico tiveram melhor sobrevida. O tratamento locorregional do carcinoma nasofaríngeo primário melhorou a sobrevida em pacientes com carcinoma nasofaríngeo metastático sincrônico que responderam à quimioterapia de indução. A irradiação local dos locais metastáticos melhorou a sobrevida dos pacientes com carcinoma nasofaríngeo metastático. A toxicidade de quimioterapia de grau 3 ou 4 alterou a sobrevida entre pacientes com carcinoma nasofaríngeo metastático sincrônico.

Experiencia en cirugía endoscópica de angiofibroma nasofaríngeo juvenil / Endoscopic surgery experience of juvenile nasopharyngeal angiofibroma

Resumen Introducción: El angiofibroma nasofaríngeo juvenil (ANJ) es un tumor benigno poco frecuente, altamente vascularizado y localmente agresivo, encontrado casi exclusivamente en pacientes masculinos adolescentes. Se presentan con epistaxis recurrente y obstrucción nasal. Objetivo: Presentar la experiencia en el tratamiento quirúrgico endoscópico exclusivo para los ANJ del equipo de rinología del Hospital del Salvador. Material y Método: Estudio descriptivo retrospectivo de corte transversal con revisión de fichas clínicas entre enero de 2011 a junio de 2017 con tratamiento quirúrgico endoscópico exclusivo para ANJ. Resultados: 16 pacientes con edad promedio de 17,2 años, 81% se presentó con obstrucción nasal y epistaxis. Todos fueron embolizados 48 o 24 horas previo a la cirugía. El tiempo quirúrgico promedio fue de 199 minutos. El sangrado estimado fue de 831 ml en promedio, con sólo un paciente con requerimientos de transfusión. El 71% no requirió taponamiento nasal anterior. El requerimiento de hospitalización fue de 4,6 días. Sólo un paciente ha tenido recurrencia al año de control. Conclusión: Los resultados en pacientes con ANJ tratados en el Hospital del Salvador reafirman el éxito de la técnica endoscópica exclusiva versus abordajes abiertos convencional, ya que presentan mejores resultados.

Abstract Introduction: The juvenile nasopharyngeal angiofibroma (ANJ) is a benign, infrequent and highly vascularized tumor. It is locally aggressive, found almost only in adolescent male patients. The classical clinical presentation is recurrent epistaxis and nasal obstruction. Aim: To review the experience of exclusive endoscopic surgery for patients with ANJ by the rhinology team of Hospital del Salvador. Material and Method: Retrospective, cross sectional, descriptive study with research of medical records of patients with exclusive endoscopic surgery treatment between January 2011 and June 2017. Results: 16 patients with a mean age of 17.2 years, 81% had nasal obstruction and epistaxis. All of them were embolized 48 to 24 hours prior surgery. Mean surgical time was 199 minutes. Estimated bleeding was 831 ml among all patients, with only one requiring blood transfusions, while 71% did not need nasal packing. Average length of hospital stay was 4.6 days. Only one patient had a recurrence after one year of surgery. Conclusion: Results of patients with ANJ treated in Hospital del Salvador reassert the success of the exclusive endoscopic surgery versus traditional open approaches, showing better results.

Transoral robotic nasopharyngectomy for local recurrent nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.

Retropharyngeal lymph node dissection in head and neck cancers treated with transoral robotic surgery / 中华肿瘤杂志

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

Function of AXL and molecular mechanisms in regulation of nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignant tumor with unique geographical and ethnic distribution characteristics. NPC is mostly found in south China and Southeast Asia, and its treatment mainly depends on radiotherapy and chemotherapy. However, NPC is usually found in the late stage, and local recurrence and distant metastasis are common, leading to poor prognosis. The receptor tyrosine kinase AXL is up-regulated in various tumors and it is involved in tumor proliferation, migration, invasion, and other processes, which are associated with poor prognosis of tumors. This study aims to detect the expression of AXL in NPC cell lines and tissues, and to investigate its biological function of AXL and the underlying molecular mechanisms in regulation of NPC.@*METHODS@#The expression levels of AXL in normal nasopharyngeal epithelial tissues and NPC tissues were analyzed by GSE68799, GSE12452, and GSE53819 data sets based on Gene Expression Omnibus (GEO) database. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between AXL and prognosis of head and neck squamous cell carcinoma (HNSC). The indicators of prognosis included overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). Western blotting assay was used to detect the AXL protein expression levels in normal nasopharyngeal epithelial cell line and NPC cell lines. Immunohistochemical method was used to detect AXL expression levels in normal nasopharyngeal epithelial tissues and NPC tissues. Cell lines with stable AXL knockdown were established by infecting 5-8F and Fadu cells with lentivirus interference vector, and cell lines with stable AXL overexpression were established by infecting C666-1 and HK-1 cells with lentivirus expression vector. Real-time PCR and Western blotting were used to detect the efficiency of knockdown and overexpression in stable cell lines. The effects of AXL knockdown or overexpression on proliferation, migration, and invasion of NPC cells were detected by CCK-8, plate colony formation, and Transwell assays, and the effect of AXL knockdown on tumor growth in nude mice was detected by subcutaneous tumor formation assay. The sequence of AXL upstream 2.0 kb promoter region was obtained by UCSC online database. The PROMO online database was used to predict AXL transcription factors with 0% fault tolerance, and the JASPAR online database was used to predict the binding sites of ETS1 to AXL. Real-time PCR and Western blotting were used to detect the effect of ETS1 on AXL protein and mRNA expression. The AXL upstream 2.0 kb promoter region was divided into 8 fragments, each of which was 250 bp in length. Primers were designed for 8 fragments. The binding of ETS1 to AXL promoter region was detected by chromatin immuno-precipitation (ChIP) assay to determine the direct regulatory relationship between ETS1 and AXL. Rescue assay was used to determine whether ETS1 affected the proliferation, migration, and invasion of NPC cells through AXL.@*RESULTS@#Bioinformatics analysis showed that AXL was highly expressed in NPC tissues (P<0.05), and AXL expression was positively correlated with OS, DFI, DSS, and PFI in HNSC patients. Western blotting and immunohistochemical results showed that AXL was highly expressed in NPC cell lines and tissues compared with the normal nasopharyngeal epithelial cell line and tissues. Real-time PCR and Western blotting results showed that knockdown and overexpression efficiency in the stable cell lines met the requirements of subsequent experiments. The results of CCK-8, plate colony formation, Transwell assays and subcutaneous tumor formation in nude mice showed that down-regulation of AXL significantly inhibited the proliferation, migration, invasion of NPC cells and tumor growth (all P<0.05), and the up-regulation of AXL significantly promoted the proliferation, migration, and invasion of NPC cells (all P<0.05).As predicted by PROMO and JASPAR online databases, ETS1 was a transcription factor of AXL and had multiple binding sites in the AXL promoter region. Real-time PCR and Western blotting results showed that knockdown or overexpression of ETS1 down-regulated or up-regulated AXL protein and mRNA expression levels. ChIP assay result showed that ETS1 bound to AXL promoter region and directly regulate AXL expression. Rescue assay showed that AXL rescued the effects of ETS1 on proliferation, migration and invasion of NPC cells (P<0.05).@*CONCLUSIONS@#AXL is highly expressed in NPC cell lines and tissues, which can promote the malignant progression of NPC, and its expression is regulated by transcription factor ETS1.

Relationship of PI3K-Akt/mTOR/AMPK signaling pathway genetic mutation with efficacy and prognosis in nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.@*METHODS@#A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time.@*RESULTS@#The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ2=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ2=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ2=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05).@*CONCLUSIONS@#The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.

Correlation of PET-CT, MRI and histopathology findings in the follow-up of patients with nasopharyngeal cancer / Correlação dos achados de PET-CT, RM e histopatologia no seguimento de pacientes com carcinoma nasofaríngeo

Abstract Introduction: Surgical treatment options are limited for nasopharyngeal cancer for many reasons including epidemiological and histological properties, proximity to important structures, heavy lymphatic drainage, and the difficulty in ensuring a safe surgical margin; therefore primary treatment is generally radiotherapy and chemotherapy. With current radiotherapy technology, oncological success has been increased and the quality of life of patients during the postradiotherapy period is improved. Objective: The role of magnetic resonance imaging and positron emission-computed tomography in the follow-up of recurrent nasopharyngeal cancer patients who were initially treated with radiotherapy was evaluated with respect to histopathological findings. Methods: A total of 110 patients with nasopharyngeal cancer who had received radiotherapy were included in the study. Patients who were suspected to have recurrence according to endoscopic nasopharyngeal examination and magnetic resonance imaging findings were requested to undergo positron emission-computed tomography. Biopsies were taken from 40 patients who had suspicious lesions in positron emission-computed tomography images. These patients' age, gender, presence/absence of contrast enhancement on magnetic resonance imaging, the SuvMax values of nasopharyngeal and neck lesions, T/N phases at initial diagnosis, histopathological recurrence, and history of neck dissection were assessed. Results: Recurrence was observed in 8 patients (20.0%). Among these, 4 (10.0%) had recurrence at the nasopharynx and 4 (10.0%) at the neck. Patients with recurrence were found to be of older age, male gender, advanced T/N phase, contrast enhancement on magnetic resonance imaging, and higher nasopharyngeal and neck SuvMax values in positron emission-computed tomography. However, these differences were not statistically significant. Only the history of neck dissection was significantly more common among those with recurrence (p < 0.001). However, in multivariate analysis, those with a nasopharyngeal SuvMax value higher than 4.58 were found to have 7.667-fold higher risk for recurrence (p = 0.036). Conclusions: Magnetic resonance imaging and positron emission-computed tomography should be evaluated together in the follow-up of nasopharyngeal cancer. Patients with minimal SuvMax 4.58 on positron emission-computed tomography after contrast enhancement in the T2 sequence on magnetic resonance imaging may considered appropriate for biopsy. Biopsies in patients with a SuvMax value lower than 4.58 can be avoided. Thus, patients avoid surgical stress and unnecessary costs.

Resumo Introdução: As opções de tratamento cirúrgico são limitadas para o carcinoma nasofaríngeo por várias razões, inclusive aspectos epidemiológicos e histológicos, proximidade de estruturas importantes, drenagem linfática carregada e dificuldade de garantir uma margem cirúrgica segura; portanto, o tratamento primário é geralmente radioterapia e quimioterapia. Com a tecnologia atual de radioterapia, o sucesso oncológico aumentou e a qualidade de vida dos pacientes durante o período pós-radioterapia é garantida. Objetivo: O papel da ressonância magnética e da tomografia computadorizada por emissão de pósitrons no seguimento de pacientes com carcinoma nasofaríngeo recorrente, inicialmente tratados com radioterapia, foi avaliado em relação aos achados histopatológicos. Método: Foram incluídos no estudo 110 pacientes com carcinoma nasofaríngeo que receberam radioterapia. Pacientes com suspeita de recorrência de acordo com o exame endoscópico nasofaríngeo e com achados de ressonância magnética foram solicitados a fazer tomografia computadorizada por emissão de pósitrons. Foram feitas biópsias de 40 pacientes com lesões suspeitas nas imagens de tomografia computadorizada por emissão de pósitrons. Os pacientes foram avaliados segundo idade, sexo, presença/ausência de realce por contraste na ressonância magnética, valores SUVmax de lesões nasofaríngeas e cervicais, estágios T/N no diagnóstico inicial, recorrência histopatológica e histórico de esvaziamento cervical. Resultados: A recorrência foi observada em 8 pacientes (20,0%). Entre esses, 4 (10,0%) apresentaram recorrência na nasofaringe e 4 (10,0%) no pescoço. Pacientes com recorrência eram do sexo masculino, apresentavam idade mais avançada, estágio avançado T/N, realce por contraste na ressonância magnética e maiores valores de SuvMax nasofaríngeo e cervical na tomografia computadorizada por emissão de pósitrons. Entretanto, essas diferenças não foram estatisticamente significantes. Apenas o histórico de esvaziamento cervical foi significantemente mais comum entre aqueles com recorrência (p < 0,001). No entanto, na análise multivariada, aqueles com um valor de SUVmax nasofaríngeo superior a 4,58 apresentaram um risco 7,667 vezes maior de recorrência (p = 0,036). Conclusão A ressonância magnética e a tomografia computadorizada por emissão de pósitrons devem ser avaliadas em conjunto no seguimento da doença. Pacientes com valor de SUVmax mínimo de 4,58 na tomografia computadorizada por emissão de pósitrons após realce com contraste na sequência T2 na ressonância magnética podem ser considerados mais adequados para biópsia. Biópsias em pacientes com um valor de SUVmax menor do que 4,58 podem ser evitadas. Dessa forma, podemos evitar o estresse cirúrgico para o paciente e custos desnecessários.

miR-18a enhances the radiosensitivity of nasopharyngeal carcinoma cells through inducing autophagy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the impacts of miR-18a overexpression or depression on the radiosensitivities of nasopharyngeal carcinoma cell line CNE1 and CNE2 and underlying mechanisms. Methods: CNE1 and CNE2 were transfected with miR-18a mimics, inhibitor and the corresponding control vectors. qRT-PCR and western blot were used to determine the ataxia telangiectasia mutated (ATM) expressions in CNE1 and CNE2. CNE1 and CNE2 with stably expressing miR-18a and miR-18a siRNA were constructed. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the impacts of the miR-18a overexpression or depression combined with irradiation on the cell growth. Flow cytometry was used to detect the cell apoptosis and cell cycle. Colony formation assay was used to evaluate the raodiosensitivities of cells. Acridine orange (AO) staining and western blot were used respectively to test the autophagy and the expressions of related proteins. Independent samples t test was used to compare the mean value between groups by using SPSS 16.0. Results: ATM mRNA was decreased significantly in CNE1 and CNE2 cells transfected with 100 or 200 nmol/L miR-18a mimics for 48 hours (CNE1: RQ=0.174±0.139 and 0.003±0.001, t=9.939 and 19 470.783;CNE2: RQ=0.024±0.008 and 0.019±0.012, t=270.230 and 137.746, respectively, all P<0.001). ATM proteins were also decreased after transfected with 100 or 200 nmol/L miR-18a mimics for 72 hours. While in the cells transfected with 100 and 200 nmol/L miR-18a inhibitor for 48 hours, the expressions of ATM mRNA were upregulated significantly (CNE1: RQ=9.419±2.495 and 2.500±1.063, t=-4.427 and -41.241; CNE2: RQ=7.210±0.171 and 115.875±15.805, t=-62.789 and -12.589, all P<0.05), and the expressions of ATM proteins increased after transfected for 72 hours. The growth of cells with miR-18a overexpression plus 4 Gy irradiation were obviously inhibited compared to that of cells with the 4Gy irradiation alone; while the growth of miR-18a-inhibited cells increased compared to that of cells with 4 Gy irradiation alone (all P<0.05). CNE1 transfected with 100 nmol/L miR-18a mimics plus 4 Gy irradiation showed the higher apoptosis rate than the cells with 4 Gy irradiation alone ((22.9±2.1)% vs. (16.3±1.0)%, t=-4.870, P<0.01). Compared to the cells with 4 Gy irradiation alone, miR-18a-overexpressed cells plus 4 Gy irradiation decreased their percentages in G1 phases ((20.2±3.0)% vs. (29.8±4.4)%, t=3.119) and G2/M phases ((21.5±0.9)% vs. (33.4±3.1)%, t=6.410, P<0.05 for both), and increased their percentages in S phases ((56.7±4.9)% vs. (36.8±6.4)%, t=-4.246, P<0.05), and these cells possessed less colony number after exposure to different doses of irradiation, more autophagy-lysosome number, and more expressions of LC3 proteins (all P<0.05). There were no significant differences in the expressions of p62 expressions between different groups of cells. Conclusion: Overexpression of miR-18a can enhance the radiosensitivities of NPC cells by targeting ATM to abrogate G1/S, G2/M arrest and to induce autophagy and apoptosis.

Clinical study on endoscopic surgery for soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the diagnosis and surgical treatment of patients with soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The clinical data of 7 NPC patients with soft tissue necrosis but not bone necrosis after radiotherapy were retrospectively analyzed.They were treated in Xiangya Hospital from 2015 to 2019. The clinical manifestations, diagnosis, treatment and prognosis were analyzed. The major clinical symptoms of the 7 patients were headache in 7 cases, hearing loss in 7 cases, long-term nasal malodor in 5 cases and epistaxis in 2 cases. All patients underwent high-resolution CT, MR and magnetic resonance angiography (MRA) before operation. All cases were treated with extended transnasal endoscopic approach under general anesthesia for resection of necrotic tissue. Five cases had their affected cartilaginous segments of the eustachian tubes partially or completely resected, 7 cases were treated with myringotomy and tube insertion, and 1 case was treated with pansinusectomy. Anti-inflammatory treatment were carried out during the perioperative period. The recovery of patients was observed and recorded through regular follow-up (from 6 months to 3 years) after the operation. Results: Nasopharynx soft tissue lesions can be seen in seven patients with bone cortex integrity by CT, and small bubble shadow can be seen at junction area between skull base soft tissue lesions and skull base bone surface.MR and MRA examination showed extensive inflammatory changes of nasopharynx. Parapharyngeal irregular necrotic cavity was found in 6 cases without central enhancement, demonstrating edema of surrounding soft tissue. The necrotic tissue of all 7 patients was surgically removed. Postoperative pathological examinations confirmed that all of them were necrotic soft and cartilaginous tissue, without tumor recurrence. The symptoms of all patients were significantly alleviated after operation. Headache was cured in 5 cases and relieved in 2 cases. Nasal malodor was cured in 4 cases and alleviated in 1 case. During the follow-up period, 5 patients survived, and 2 patients who had their eustachian tube reserved died. One of them died of nasopharyngeal hemorrhage caused by recurrent nasopharyngeal necrosis 3 months after the operation. Another case died of severe intracranial infection 6 months after operation. Conclusions: The diagnosis of skull base soft tissue necrosis after radiotherapy for nasopharyngeal carcinoma needs comprehensive analysis of radiotherapy history, clinical manifestations and imaging examination. High resolution CT, MR and MRA of skull base are very important for diagnosis. Early active removal of large-scale necrotic lesions under endoscope and partial or total resection of eustachian tube cartilage according to the involvement of eustachian tube cartilage is effective means of controling skull base soft tissue necrosis after radiotherapy. The effective means of necrosis can improve the quality of life of patients.

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma / 中华医学杂志(英文版)

BACKGROUND@#The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC.@*METHODS@#We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS).@*RESULTS@#The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019).@*CONCLUSIONS@#CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

Epstein / 中南大学学报(医学版)

Epstein-Barr virus (EBV), a definite tumorigenic virus, is closely related to the development of nasopharyngeal cancer, gastric cancer, lymphoma and other tumors. EBV encodes a total of 44 mature microRNAs, which can regulate the expression of virus and host genes. EBV-encoded microRNAs and their regulated target molecules participate in the biological functions of tumor apoptosis, proliferation, invasion, and metastasis during tumorigenesis and development, and play an important role in the development of tumor.

Application of New Posture Fixation Device Compatible with Magnetic Resonance Simulation Positioning in Head and Neck Radiotherapy / 中国医疗器械杂志

OBJECTIVE@#Whether the developed new type of radiotherapy auxiliary fixation device compatible with the head and neck joint coil can improve the quality of magnetic resonance images in radiotherapy and verify whether it can be applied to clinical treatment.@*METHODS@#The clinical trial selected patients with brain metastases and nasopharyngeal cancer patients, using thermoplastic film and head and shoulder molds for posture fixation, and treatment on the ELekta Versa accelerator. SPSS 20.0 statistical software was used to analyze the data. The measurement data were expressed by @*RESULTS@#Considering the influence of the outer contour of the device, the target dose meets the clinical requirements. The setting error is less than 2 mm in the three translation directions, and the rotation error is less than 2@*CONCLUSIONS@#There is no statistical difference between the treatment results of patients using the new type of fixation device and the conventional method. The target area threatens the organ dose, and the positioning error meets the treatment requirements.

Effectiveness of simplified predictive intubation difficulty score and thyromental height in head and neck surgeries: an observational study / Eficácia do escore simplificado preditivo de dificuldade de intubação e da altura tiromentoniana em cirurgias de cabeça e pescoço: estudo observacional

Abstract Background and objectives: In this study, we aimed to investigate the predictive value of different airway assessment tools, including parts of the Simplified Predictive Intubation Difficulty Score (SPIDS), the SPIDS itself and the Thyromental Height Test (TMHT), in intubations defined as difficult by the Intubation Difficulty Score (IDS) in a group of patients who have head and neck pathologies. Methods: One hundred fifty-three patients who underwent head and neck surgeries were included in the study. The Modified Mallampati Test (MMT) result, Thyromental Distance (TMD), Ratio of the Height/Thyromental Distance (RHTMD), TMHT, maximum range of head and neck motion and mouth opening were measured. The SPIDSs were calculated, and the IDSs were determined. Results: A total of 25.4% of the patients had difficult intubations. SPIDS scores >10 had 86.27% sensitivity, 71.57% specificity and 91.2% Negative Predictive Value (NPV). The results of the Receiver Operating Curve (ROC) analysis for the airway screening tests and SPIDS revealed that the SPIDS had the highest area under the curve; however, it was statistically similar to other tests, except for the MMT. Conclusions: The current study demonstrates the practical use of the SPIDS in predicting intubation difficulty in patients with head and neck pathologies. The performance of the SPIDS in predicting airway difficulty was found to be as efficient as those of the other tests evaluated in this study. The SPIDS may be considered a comprehensive, detailed tool for predicting airway difficulty.

Resumo Justificativa e objetivos: Neste estudo, avaliamos o valor preditivo de diferentes ferramentas de avaliação das vias aéreas, incluindo componentes do Escore Simplificado Preditivo de Intubação Difícil (ESPID), o próprio ESPID e a Medida da Altura Tireomentoniana (MATM), em intubações definidas como difícies pelo Escore de Dificuldade de Intubação (EDI) em um grupo de pacientes com patologia de cabeça e pescoço. Método: Incluímos no estudo 153 pacientes submetidos a cirurgia de cabeça e pescoço. Coletamos os resultados do Teste de Mallampati Modificado (TMM), Distância Tireomentoniana (DTM), Razão Altura/Distância Tireomentoniana (RADTM), MATM, amplitude máxima de movimentação da cabeça e pescoço e da abertura da boca. Os ESPIDs foram calculados e os EDIs, determinados. Resultados: Observamos intubação difícil em 25,4% dos pacientes. Os escores de ESPID > 10 tiveram sensibilidade de 86,27%, especificidade de 71,57% e valor preditivo negativo de 91,2% (VPN). O resultado da análise da curva de operação do receptor (curva ROC) para os testes de avaliação das vias aéreas e ESPID mostrou que o ESPID tinha a maior área sob a curva; no entanto, foi estatisticamente semelhante a outros testes, exceto para o TMM. Conclusões: O presente estudo demonstra o uso prático do ESPID na previsão da dificuldade de intubação em pacientes com patologia de cabeça e pescoço. O desempenho do ESPID na predição de via aérea difícil mostrou-se tão eficiente quanto os demais testes avaliados neste estudo. O ESPID pode ser considerado ferramenta abrangente e detalhada para prever via aérea difícil.

A comparison of cisplatin cumulative dose and cisplatin schedule in patients treated with concurrent chemo-radiotherapy in nasopharyngeal carcinoma / Comparação da dose cumulativa de cisplatina e esquema de tratamento em pacientes com carcinoma nasofaríngeo tratados concomitantemente com quimiorradioterapia

Abstract Introduction: Three-weekly cisplatin dose is accepted for standard treatment for concurrent chemo-radiotherapy in nasopharyngeal carcinoma. However, different chemotherapy schedules are presented in the literature. Objective: We intend to compare toxicity and outcomes of high dose 3-weekly cisplatin versus low dose weekly-cisplatin and cumulative dose of cisplatin in the patients with nasopharyngeal carcinoma. Methods: 98 patients were included in the study, between 2010 and 2018. Cumulative doses of cisplatin (≥200 mg/m2 and <200 mg/m2) and different chemotherapy schedules (weekly and 3-weekly) were compared in terms of toxicity and survival. Besides prognostic factors including age, gender, T category, N category and radiotherapy technique were evaluated in uni-multivariate analysis. Results: Median follow-up time 41.5 months (range: 2-93 months). Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 68.9% vs. 90.3% (p = 0.11); 66.2% vs. 81.6% (p = 0.15); 87.3% vs. 95.7% (p = 0.18); 80.1% vs. 76.1% (p = 0.74) for the group treated weekly and 3 weekly, respectively. There was no statistically significant difference between groups. Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 78.2% vs. 49.2% (p = 0.003); 75.8% vs. 47.9% (p = 0.055); 91% vs. 87.1% (p = 0.46); 80% vs. 72.2% (p = 0.46) for the group treated ≥200 mg/m2 and <200 mg/m2 cumulative dose cisplatin. There was statistically significant difference between groups for overall survival and there was close to being statistically significant difference between groups for local relapse-free survival. Age, gender, T category, N category, chemotherapy schedules were not associated with prognosis in the uni-variety analysis. Radiotherapy technique and cumulative dose of cisplatin was associated with prognosis in uni-variate analysis (HR = 0.21; 95% CI: 0.071-0.628; p = 0.005 and HR = 0.29; 95% CI: 0.125-0.686; p = 0.003, respectively). Only cumulative dose of cisplatin was found as an independent prognostic factor in multivariate analysis (HR = 0.36; 95% CI: 0.146-0.912; p = 0.03). When toxicities were evaluated, such as hematological toxicity, dermatitis, mucositis, nausea and vomiting, there were no statistically significant differences between cumulative dose of cisplatin groups (<200 mg/m2 and ≥200 mg/m2) and chemotherapy schedules (3-weekly and weekly). But malnutrition was statistically significant higher in patients treated with 3-weekly cisplatin compared with patients treated with weekly cisplatin (p = 0.001). Conclusion: A cisplatin dose with ≥200 mg/m2 is an independent prognostic factor for overall survival. Chemotherapy schedules weekly and 3-weekly have similar outcomes and adverse effects. If patients achieve ≥200 mg/m2 dose of cumulative cisplatin, weekly chemotherapy schedules may be used safely and effectively in nasopharyngeal carcinoma patients.

Resumo Introdução: Três doses semanais de cisplatina com quimiorradioterapia concomitante são aceitas como o tratamento-padrão para carcinoma nasofaríngeo. No entanto, diferentes esquemas quimioterápicos são recomendados na literatura científica. Objetivo: Comparar a toxicidade e os resultados de 3 doses altas semanais de cisplatina versus dose baixa semanal de cisplatina em pacientes com carcinoma nasofaríngeo e verificar a dose cumulativa de cisplatina. Método: Foram incluídos 98 pacientes, entre 2010 e 2018. As doses cumulativas de cisplatina (≥ 200 mg/m2 e < 200 mg/m2) e diferentes esquemas de quimioterapia (semanal e a cada 3 semanas) foram comparadas em termos de toxicidade e sobrevida. Além disso, fatores prognósticos, inclusive idade, sexo, categoria T, categoria N e técnica de radioterapia, foram avaliados na análise uni-multivariada. Resultados: O tempo médio de seguimento foi de 41,5 meses (intervalo: 2-93 meses). Sobrevida global de cinco anos, sobrevida livre de recidiva local, sobrevida livre de recidiva regional e sobrevida livre de metástases a distância foram: 68,9% vs. 90,3% (p = 0,11); 66,2% vs. 81,6% (p = 0,15); 87,3% vs. 95,7% (p = 0,18); e 80,1% vs. 76,1% (p = 0,74) para os grupos tratados semanalmente e 3 x/semana, respectivamente. Não houve diferença estatisticamente significante entre os grupos. Taxas de sobrevida global, sobrevida livre de recidiva local, sobrevida livre de recidiva regional e sobrevida livre de metástases a distância em cinco anos foram; 78,2% vs. 49,2% (p = 0,003); 75,8% vs. 47,9% (p = 0,055); 91% vs. 87,1% (p = 0,46); 80% vs. 72,2% (p = 0,46) para o grupo tratado com ≥ 200 mg/m2 e < 200 mg/m2 de dose cumulativa de cisplatina. Houve diferença estatisticamente significante entre os grupos para sobrevida global e houve uma diferença quase estatisticamente significante entre os grupos para sobrevida livre de recidiva local. Idade, sexo, categoria T, categoria N e esquemas de quimioterapia não foram associados ao prognóstico na análise univariada. A técnica de radioterapia e dose cumulativa de cisplatina foram associadas ao prognóstico na análise univariada (HR = 0,21; IC 95%: 0,071 ± 0,628; p = 0,005 e HR = 0,29; IC 95%: 0,125 ± 0,686; p = 0,003, respectivamente). Apenas a dose cumulativa de cisplatina foi considerada um fator prognóstico independente na análise multivariada (HR = 0,36; IC 95%: 0,146 ± 0,912; p = 0,03). Quando as toxicidades foram avaliadas, como toxicidade hematológica, dermatite, mucosite, náusea e vômito, não houve diferença estatisticamente significante entre a dose cumulativa dos grupos cisplatina (< 200 mg/m2 e ≥ 200 mg/m2) e esquemas de quimioterapia (semanal e a cada 3 semanas). Entretanto, a desnutrição foi estatisticamente maior em pacientes tratados com cisplatina a cada 3 semanas em comparação com pacientes tratados com cisplatina semanalmente (p = 0,001). Conclusão: Uma dose de cisplatina ≥ 200 mg/m2 é fator prognóstico independente para sobrevida global. Os esquemas de quimioterapia semanais e a cada 3 semanas têm resultados e efeitos adversos semelhantes. Se os pacientes atingirem uma dose cumulativa ≥ 200 mg/m2 de cisplatina, os esquemas semanais de quimioterapia podem ser usados com segurança e eficácia em pacientes com carcinoma nasofaríngeo.

Cáncer de nasofaringe, una revisión de la literatura / Nasopharyngeal Cancer, a literature review

Resumen Introducción: El cáncer de nasofaringe es una patología poco común que tiene gran impacto en la calidad de vida de los pacientes. Con el advenimiento de nuevos esquemas de tratamiento se ha logrado mejorar el pronóstico con un menor índice de morbilidad. Esta revisión describe la perspectiva actual del cáncer de nasofaringe, basado en la literatura reciente y la disponibilidad de recursos para su tratamiento en una institución médica de Medellín, Colombia. Materiales y Método: Se realizó una búsqueda bibliográfica que incluyó artículos desde 1986 hasta 2018 en diferentes bases de datos como MEDLINE, EBSCO y LILACS. Se incluyó literatura escrita en inglés o español, utilizando como términos MESH neoplasias de nasofaringe, diagnóstico y terapéutica. Resultados: La evaluación diagnóstica oportuna del cáncer de nasofaringe es de vital importancia al proporcionar una estrategia de tratamiento efectiva con menor morbimortalidad. Según la experiencia institucional de los autores, en las etapas clínicas tempranas, se sugiere la radioterapia radical como modalidad única y en etapas intermedias-avanzadas los tratamientos combinados con quimioterapia-radioterapia concomitante o secuencial dependiendo de cada paciente y quimioterapia única en pacientes metastásicos a distancia. Conclusiones: Acorde con el análisis de la literatura y evidencia existente, las estrategias utilizadas son adaptadas a los alcances de la institución como ente de alto nivel en el sector salud. La cirugía representa un papel relevante en la enfermedad recurrente resecable ya sea con técnica endoscópica o abierta. Es importante recordar que la morbilidad postoperatoria no es inocua, y en ocasiones sobrepasa el beneficio obtenido.

Introduction: Nasopharyngeal cáncer is a rare disease that has a huge impact on the quality of life. Survival rates are steadily improving due to new treatments with a lower morbidity index. This review describes the current perspective of nasopharyngeal cancer, based on recent literature and the availability of resources for treatment in the different specialties of an institution in Medellin, Colombia. Materials and Method: A literature review was carried out, including articles from 1986 to 2017 in different databases such as MEDLINE, EBSCO and LILACS. Written literature in English or Spanish was included, using MESH terms as Nasopharyngeal, diagnostic and therapeutic neoplasms. Results: Nasopharyngeal cancer timely diagnostic is of vital importance. According to the institutional experience, in early clinical stage radiotherapy is suggested as a single modality. Intermediate stages treatments options are concurrent chemo radiotherapy or sequential radiotherapy according to each patient case. In distant metastatic stage single chemotherapy is used. Conclusions: According to existing evidence strategies used are adapted to the scope of the institution as a high-level entity in health sector. Surgery represents a relevant role in recurrent resecable disease with either endoscopic or open technique. It is important to remember that postoperative morbidity is not harmless, and sometimes exceeds the benefit obtained.

In vivo and in vitro study of co-expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma / Estudo in vivo e in vitro da coexpressão de LMP1 e Cripto-1 em carcinoma nasofaríngeo

Abstract Introduction: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. Objective: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. Methods: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n = 42) and nasopharyngitis patients (n = 22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. Results: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p < 0.05). Their expression in nasopharyngeal carcinoma with metastasis were significantly higher than that without metastasis (p < 0.05), which was correlated with TNM staging (p < 0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells. Conclusions: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é um tumor maligno derivado do epitélio de localização anatômica recôndita e sintomas iniciais atípicos; quando diagnosticado, frequentemente invasão e metástases já ocorreram. Isso requer uma melhor compreensão do seu mecanismo de desenvolvimento, identificação dos marcadores diagnósticos e desenvolvimento de novas estratégias de tratamento. Objetivo: Estudar a relação de LMP1 e Cripto-1 no carcinoma nasofaríngeo. Método: A expressão de LMP1 e Cripto-1 em espécimes obtidos de pacientes com carcinoma de nasofaringe (n = 42) e pacientes com nasofaringite (n = 22) foi analisada. A expressão de LMP1 e Cripto-1 em células LMP1-negativas e LMP1-positivas (CNE1-LMP1) também foi analisada. Resultados: A expressão de LMP1 e Cripto-1 foi significantemente maior na presença de carcinoma nasofaríngeo do que na nasofaringite (p < 0,05). Sua expressão em carcinomas com metástase foi significantemente maior do que em casos sem metástase (p < 0,05), o que se correlacionou com o estadiamento TNM (p < 0,05). Uma alta expressão de Cripto-1 e alta taxa de proliferação foram observadas nas células CNE1-LMP1. Conclusões: A expressão de LMP1 e Cripto-1 é positivamente relacionada com carcinoma nasofaríngeo. Sua coexpressão pode ser atribuída à proliferação e metástase do tumor.

Plasmocitoma extramedular de laringe: a propósito de un caso / Extramedullary plasmacytoma of the larynx: a case report

Resumen Los plasmocitomas solitarios son una rara forma de presentación de neoplasias de células plasmáticas. Deben ser diferenciados del mieloma múltiple en el momento del diagnóstico y realizar un seguimiento estricto por el riesgo de transformación a mieloma. La localización de los mismos en la laringe es muy inusual, dado que sólo se han publicado 56 casos. Se presenta el caso de una paciente con un plasmocitoma extramedular de laringe que se trató mediante cirugía y radioterapia. Se revisan los criterios diagnósticos y los problemas terapéuticos.

Abstract Solitary plasmacytomas are a rare form of plasma cell neoplasms. They should be differentiated from multiple myeloma at the time of diagnosis and strictly monitored for the risk of transformation to myeloma. Their location in the larynx is very unusual, since only 56 cases have been published. We present the case of a patient with extramedullary plasmacytoma of the larynx that has been treated with surgery and radiotherapy. We reviewed the literature for diagnostic criteria and therapeutic problems.