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Juvenile nasopharyngeal angiofibroma (JNA) is a benign, vascular, tumour primarily occuring in adolescent males. Juvenile nasopharyngeal angiofibroma is normally unilateral, originating from the sphenopalatine artery. Two separate masses arising from both sides are exceedingly rare. We report a case of a 29-year-old male presented with increasing nasal obstruction, recurrent epistaxis, and a mass on his left buccal. Computed tomography and magnetic resonance imaging revealed non-contiguous tumours on the right nasopharynx and on the left buccal. Angiography showed independent vascular supplies from each side with no bilateral supply noted. Preoperative embolization on both vascular supplies was done, followed by surgical removal of the tumours with no major complication. Histopathological examination showed both are JNA. No major complications were noted. This case discusses how suspecting bilateral juvenile angiofibroma in a patient with two non-contiguous masses in head and neck region is recommended. Proper diagnosis of bilateral JNA can lead to better management and results.

Background Studies suggest that the most common type of nasopharyngeal carcinoma (NPC) is WHO-3, which is strongly associated with Epstein-Barr virus (EBV). Objective To assess NPC patient characteristics in a national general referral hospital in Indonesia, with regards to EBV DNA load and treatment response. Methods Twenty-three pediatric patients diagnosed with NPC were included in the study. Data collected were history, physical examination, tissue biopsy, CT scan, staging and EBV DNA load from nasopharyngeal (NP) brushing as well as blood specimens. The NP brushing, blood specimens and CT scan evaluations were done two months post-treatment. Results Pediatric patients with symptoms such as blood tinged secretion, lymph node enlargement, and nasal congestion were more likely to have higher EBV DNA loads in their NP brushings (P

Background Nasopharyngeal cancer is endemic to Southeast Asia. However, there is limited clinical evidence of nasopharyngeal cancer in Indonesia, which has the largest population in Southeast Asia. Methods Patterns of care and treatment outcomes in 428 patients with newly-diagnosed and pathologically-confirmed nasopharyngeal cancer were retrospectively analyzed. Results Concurrent chemo-radiotherapy (CCRT) was the first-line treatment for stages I-IVB diseases. The 2-year overall survival (OS) of all patients were 100.0%, 100.0%, 93.8%, 86.2%, 82.9%, and 62.4% for stages I, II, III, IVA, IVB, and IVC, respectively. The 2-year OS of CCRT-treated patients were 100.0%, 100.0%, 92.6%, 82.4%, and 78.3% for stages I, II, III, IVA, and IVB, respectively. Conclusion The patterns of care and treatment outcomes were potentially consistent with world standards, needing future validation. This is the largest study of newly diagnosed nasopharyngeal cancer in Indonesia, a huge disease burden, providing an important basis for the clinical management of this disease.

Cell‐free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle‐bound form, represent promising minimally‐invasive cancer biomarkers. However, a highly abundant non‐tumor background in human plasma and serum complicates the discovery and detection of tumor‐selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus‐encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq‐based EBV miRNA profiles differ between NPC patients, suggesting inter‐tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT‐PCR assays that EBV miRNAs BART7‐3p, BART9‐3p and BART13‐3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late‐stage NPC patients. Increased levels of BART7‐3p, BART9‐3p and particularly BART13‐3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV‐infections reveals a superior diagnostic performance of EBV miRNAs over anti‐EBNA1 IgA serology and EBV‐DNA load (AUC 0.87–0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV‐BART13‐3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV‐bound BART13‐3p in circulation is a promising, NPC‐selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions., What's new? Analysis of DNA from human tumor viruses in patient blood is a non‐invasive screening method for individuals at risk for developing cancer. A drawback is over‐diagnosis as these sensitive methods also detect non‐cancer‐related infections. Here the authors show by RNA sequencing and PCR amplification that a microRNA (BART13‐3p) encoded by the Epstein–Barr Virus (EBV) is associated with circulating vesicles in patients with nasopharyngeal carcinoma, thus distinguishing between cancer and non‐cancer‐related EBV infections.

Cases of Human papillomavirus (HPV)-associated oral and oropharyngeal cancer are increasing. Proper diagnostic tools are required to detect HPV among patients, especially in areas where high technology is lacking.To provide mapping of HPV prevalence in Southeast Asia and to determine the effectivity of p16 as a surrogate biomarker for HPV infection in oral and oropharyngeal cancer.Medical records of 56 patients diagnosed with oral and oropharyngeal squamous cell carcinomas (SCC) were reviewed. HPV PCR DNA and p16 immunohistochemistry (IHC) examination were performed to detect HPV positivity.HPV PCR prevalence in oropharyngeal SCC is 42.9% and 28.6% in oral SCC. P16 IHC has 67% sensitivity and 75% specificity in detecting HPV in oropharyngeal cancer, and 33% and 72% in oral cancer.We conclude that p16 IHC with a 5% cut-off can be used as a surrogate biomarker for oropharyngeal SCC, but not oral SCC, in areas where resources are restricted. However, further diagnostic tools may be needed.

Tumor microenvironment have been implicated in many kind of cancers to hold an important role in determining treatment success especially with immunotherapy. In nasopharyngeal cancer, the prognostic role of this immune cells within tumor microenvironment is still doubtful. We conducted a study that included 25 nasopharyngeal cancer biopsy specimens to seek a more direct relationship between tumor infiltrating immune cells and tumor progression. Apart from that, we also checked the PD-L1 protein through immunohistochemistry. The PD-L1 was positively expressed in all our 25 samples with nasopharyngeal cancer WHO type 3 histology. Majority samples have >50% PD-L1 expression in tumor cells. We also found that denser local tumor infiltrating immune cells population have relatively much smaller local tumor volume. The inverse applied, with the mean local tumor volumes were 181.92 cm3 ± 81.45 cm3, 117.13 cm3 ± 88.72 cm3, and 55.13 cm3 ± 25.06 cm3 for mild, moderate, and heavy immune cells infiltration respectively (p = 0.013). Therefore, we concluded that tumor infiltrating immune cells play an important role in tumor progression, hence evaluating this simple and predictive factor may provide us with some valuable prognostic information.

Nasopharyngeal carcinoma (NPC) is a prevalent disease in certain geographical locations especially in South East Asia. The majority of patients will present with complaints of nasal symptoms, aural as well as neck mass. Other clinical manisfestations are also possible if the disease has spread to the surrounding structures, with the involvement of multiple cranial nerve palsies. Since sometimes nasal complaints can be subtle, a high index of suspicion is crucial. The choice of treatment for NPC is chemoradiation either in a single mode or concurrently. Of note, patients also experience numerous complications from chemoradiation that impairs quality of life.

Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in Indonesia. NPCpresents numerous challenges from non-specific signs and symptoms until lack of awareness from generalpractitioners (GP), which lead to late or missed diagnosis. Early diagnosis and prevention are proposedas the best solutions for this problem. In order to do that, we need a complete and well-managed patients’data. This study aims to reveal the demographic, clinical and histopathologic characteristics of NPC inIndonesia. A cross-sectional study was conducted by collecting medical records of all NPC patients in 2010from Otorhinolaryngology Department of Dr. Cipto Mangunkusumo National Hospital. The extracted datawere then analyzed to describe the problem of NPC in Indonesia. Out of 167 patients, 68.3% of the patientsare male and most of them are Sundanese and Javanese. Palpable lump in the neck is the most commoncomplaint in presentation (58.1%), followed by nasal congestion (49.1%). Salted fish consumption was themost prevalent risk factor (29.9%). Based on the histopathologic findings, 75.4% of the cases were classifiedas WHO-3 and around half of the patients (51%) were in stage IV upon diagnosis. Studying demographic andclinical characteristics of NPC patients is the first step to overcome problems caused by NPC in Indonesia.

Introduction Nasopharyngeal cancer in Indonesia has a poor survival rate and there is only few studies regarding nasopharyngeal cancer in Indonesia. Therefore, this study was made to present Indonesian nasopharyngeal cancer data with special focus on survival of nasopharyngeal cancer profile that receives radiation therapy. Methods This was a retrospective study conducted in the Department of Radiation Oncology, Dr. Cipto Mangunkusumo Hospital (RSCM). Moreover, survival analysis was done using Kaplan Meier, log rank and cox regression test. Results A total of 398 patients were included with the median follow-up time of 16 (0–65) months. The 3-year survival in patients with stage I–III was >50% while the survival of 5 years was >50% only in early stage patients. The median survival for men was 46 months and for women 42 months. For OTT ≤ 49 days survival of 3 years and 5 years is 67.1%. Stage III–IVB, size N2-N3, and overall treatment time >49 days were the prognostic factors for nasopharyngeal cancer patients. After multivariate analysis, only stage III–IVB was statistically significant as a prognostic factor independent of survival. Conclusion Most of nasopharyngeal cancer patient came in advanced stage. The median time needed for patients to get radiation therapy and median OTT were good. Only stage III–IVB was statistically significant as a prognostic factor independent of survival.

Nasopharyngeal cancer is a cancer closely related to Epstein-Barr virus (EBV) infection. EBV protein has been shown to be related to various oncogenic development. Suppression of tumor suppressor genes, upregulating molecules to prevent immune attack, downregulating pro-apoptotic proteins, and stimulating local immune suppressive environment are among some roles that EBV proteins can exert on host cells. All those factors combined together with underlying genetic susceptibility of host cells further increase the chance of nasopharyngeal cancer development. Approach targeting those carcinogenesis pathways has been tested with marginal benefit. A newer approach boosting immune cells to increase recognition of tumor antigen and promoting cytotoxic T cell attack has shown promising clinical benefit. Further combination of those immunotherapies with other modality, in particular radiotherapy, has resulted in amplification of cancer killing.

Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV-DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP-biopsy specimens from patients suspected of having NPC. We observed non-fragmented and Cp-promotor methylated EBV-DNA in both NP brushings and biopsies suggestive of tumor origin. Using quantitative RT-PCR we determined expression levels of 7 critical latent (EBER1, Qp-EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) and 5 lytic (Zta, Rta, TK, PK and VCA-p18) RNA transcripts. Although latent and early lytic RNA transcripts were frequently detected in conjunction with high EBV viral load, in both brushings and biopsies the latent transcripts prevailed and reflected a typical NPC-associated latency-II transcription profile without EBNA2. Late lytic RNA transcripts were rare and detected at low levels mainly in NP brushings, suggestive of abortive viral reactivation rather than complete virus replication. EBV-IgA serology (EBNA1, VCA, Zta) did not correlate to the level of viral reactivation in situ. Overall, viral RNA profiling, DNA fragmentation and methylation analysis in NP brushings and parallel biopsies indicate that NP brush sampling provides a true and robust indicator of NPC tumor presence.

Nasopharyngeal carcinoma (NPC) is the most frequent head and neck malignancy in Indonesia. Misdiagnosis of NPC is common because of unspecific symptoms as unilateral ear complaint. This case reminds doctors of the early symptoms of NPC and of other factors which lead to misdiagnosis and addresses also patients and their families. Reported is a 44 years old man with unilateral ear disorder that had been treated by otorhinolaryngologists, an ophthalmologist, a neurologist, and dentist first, but diagnosed with nasopharyngeal carcinoma stage IVA (T4N1M0) one year later. NPC has unspecific early symptoms such as unilateral ear disorder. Primarily doctors, but also patients and their families should be aware of unilateral ear complaint.Keywords: misdiagnosis, nasopharyngeal carcinoma, unilateral ear disorders

Background Molecular and biological characterization of nasopharyngeal cancer (NPC) is scarce. Clinical trials of emerging treatment such as immunotherapy for NPC in endemic area is lacking. Currently the most extensively studied immune related molecule that potentially become the target for treatment is PD-1/PD-L1. PD-L1 profile of NPC patients in Indonesia has never been studied before. This study aimed to elucidate PD-L1 profile from NPC specimens in Indonesia. Methods Nasopharyngeal biopsy specimen was taken for PD-L1 protein examination with enzyme-linked immunosorbent assay (ELISA) method. Tissue specimen was homogenized and then ELISA test was conducted using ABCAM AB214565 kit. All protocols from the manufacturer kit was followed. Total protein concentration from homogenized tissue specimen was obtained through Bradford protein assay method. Then, PD-L1 concentration per mg protein of tissue specimen was calculated. Results Twenty-four nasopharyngeal biopsy specimens was obtained. The average age of all patients was 45 years old. Sixteen (66.67%) out of 24 specimens were confirmed histologically to be undifferentiated nasopharyngeal carcinoma. The rest, 8 other specimens have normal histology. Average PD-L1 concentration from NPC specimens was 2,186.67 ± 1,399.32 pg/mg protein (Range: 461.76 to 4,805.85 pg/mg protein). Average PD-L1 concentration from non NPC specimens was 612.43 ± 314.04 pg/mg protein (Range: 326.87 to 1,155.19 pg/mg protein). Conclusions From this preliminary result, PD-L1 protein (both in tumor cells and in immune cells) from NPC specimens has been shown to be elevated compared to normal nasopharyngeal epithelium. This finding indicate that further work is warranted to test anti PD-L1 drug for NPC patients that has failed all the standard treatment. Furthermore, our upcoming work would be exploring relationship between PD-L1, EBV, and tumor microenvironment from our NPC specimens. Legal entity responsible for the study The authors. Funding University of Indonesia. Disclosure All authors have declared no conflicts of interest.

Purpose: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and highly prevalent in Indonesia. EBV-DNA load can be used for early diagnosis and may have prognostic value. In this study, EBV-DNA load was evaluated in minimal invasive nasopharyngeal (NP) brushings and whole blood for initial diagnosis and therapy assessment against the standard-of-care diagnosis by biopsy with EBV-RISH and standard EBV-IgA serology. Experimental Design: NP brushings and blood samples were collected from 289 consecutive ENT patients suspected of NPCs and 53 local healthy controls. EBV-DNA load was quantified by real-time PCR and serology by peptide-based EBV-IgA ELISA. Tissue biopsies were examined by routine histochemistry and by EBER RNA in situ hybridization. Results: Repeated NP brushing was well tolerated by patients and revealed high viral load in the 228 NPC cases at diagnosis than 61 non-NPC cancer cases and healthy controls (P < 0.001). The diagnostic value of EBV-DNA load in blood and EBV-IgA serology was inferior to the NP brush results. The level of EBV-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage. EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P = 0.001 and P = 0.005, respectively), which was not reflected in EBV-IgA serology. Conclusions: NP brush sampling combined with EBV-DNA load analysis is a minimal invasive and well-tolerated diagnostic procedure, suited for initial diagnosis and follow-up monitoring of NPCs. Clin Cancer Res; 19(8); 2175–86. ©2013 AACR.

Objective: To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia. Design: The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities. Participants: 1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC. Results: 703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p

BackgroundNasopharyngeal carcinoma (NPC) is endemic in Indonesia and 20% of the patients are diagnosed before the age of 31. This study evaluates presentation and treatment outcome of young patients in Jakarta, in a tertiary referral centre.MethodsForty-nine patients under the age of 31, diagnosed with NPC between July 2004 and January 2007, were evaluated. Baseline data included histological type, stage of disease and presenting symptoms. We intended to follow all patients after diagnosis to reveal treatment outcome and overall survival (OS).ResultsAll but two patients had advanced stage disease (94%), 7 (14%) had distant metastasis. The median interval between start of complaints and diagnosis was 9 months. Forty-two patients were planned for curative intent treatment. Eleven patients (26%) never started treatment, 2 patients did not complete treatment and 3 patients did not return after finishing treatment. Four patients died before radiation could start. Three patients died within 4 months after treatment. Nine patients (21%) had a complete response. Due to the high number of patients who were lost to follow-up (LFU), OS was analyzed as follows: a best-case (patients censored at last contact) and a worst-case scenario (assuming that patients who did not finish treatment or had disease at last contact would have died). The 2-year OS for patients without distant metastases was 39-71%.ConclusionTreatment outcome for young patients with NPC in this institute was poor. Improvement can be achieved when NPC is diagnosed at an earlier stage and when there is better treatment compliance.

UNLABELLED:In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. METHODS:Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. RESULTS:The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p

Background: The treatment of persistent and recurrent nasopharyngeal carcinoma (NPC) remains a challenge, especially in Indonesia. We investigated the safety and efficacy of temoporfin mediated photodynamic therapy (PDT) for patients with local persistent and recurrent NPC. Material and methods: Twenty-two patients with persistent and recurrent NPC (maximum tumor depth

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p