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BACKGROUND: The risk-combination of genetic or familial history, environmental risk factors, and EBV infection might cause nasopharyngeal carcinogenesis. The serum antibody for EBV IgA, namely, EBNA1+VCA-p18 has a good sensitivity as an early diagnostic test for nasopharyngeal carcinoma (NPC). AIM: This study aims to determine the correlation between risk factors and histopathological typing of NPC and also the correlation between the IgA [EBNA-1 + VCA p-18] ELISA and histologic type. METHODS: A cross-sectional method was used on 108 NPC patients which filled a questionnaire through an in-depth interview on the family condition to cancer, habit/lifestyle, and environmental risks. A total of 47 subjects were willing to donate blood samples for IgA [EBNA1 + VCA p-18] ELISA. Furthermore, Kendall’s tau-b (τ) correlation test was performed on NPC keratin type (WHO-1) and non-keratin (WHO-2 and 3). RESULTS: The results showed that the family history of non-keratinized NPC was associated with NPC WHO-3 as demonstrated by τ = 0.473, as well as salt-eating with τ = 0.334, smoked/grilled fish/meat eating τ = 0.205, instant noodle-eating τ = 0.356, consuming canned/packaged canned foods τ = 0.240, and flavored food eating habits τ = 0.364, along with passive smoking τ = 0.377, and chronic nasopharyngeal infection τ = 0.530. The IgA titers, namely, [EBNA1 + VCA p-18] ELISA for non-keratin type NPC was greater than the keratin type; however, it was not related to WHO-3 NPC as indicated by τ = 0.376, and p = 0.011 put this underlying before however. CONCLUSIONS: The positivity of IgA [EBNA-1 + VCA p-18] ELISA does not correlate with the non-keratin type histologic NPC, family history, as well as salt-eating, instant noodle, and flavored food eating habits, along with passive smoking and nasopharyngeal infection.

The marine Streptomyces sp. strain GMY01 was isolated from Indonesian marine sediment. Genome mining analysis revealed that GMY01 has 28 biosynthetic gene clusters, dominated by genes encoding nonribosomal peptide synthetase and polyketide synthase.

PurposeThis study aimed to determine the survival outcome and prognostic factors of patients with nasopharyngeal cancer accessing treatment in Yogyakarta, Indonesia.MethodsData on 759 patients with NPC diagnosed from 2007 to 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic, clinicopathology and treatment parameters. Multivariable analyses were implemented using semi-parametric Cox proportional hazards modelling and fully parametric survival analysis.ResultsThe median time of observation was 14.39 months. In the whole cohort the median observed survival was 31.08 months. In the univariable analysis, age, education status, insurance type, BMI, ECOG index, stage and treatment strategy had an impact on overall survival (OS) (p values ConclusionsMedian OS for the cohort was low compared to those reported in both endemic and non-endemic regions. By combining the findings of multivariable analyses, we showed that age, education status, ECOG index, stage and first treatment modality were independent predictors for the OS.

Background The survival of patients with nasopharyngeal cancer (NPC) have been reported in endemic and non-endemic regions. However, this has never been analyzed in Indonesian cases although this malignancy is endemic. This study aimed to perform survival analysis of the local cases and determine the prognostic factors. Methods A total of 767 patients with NPC diagnosed from January 2007 to December 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic parameters, clinicopathology features and treatment strategy. Kaplan-Meier method and the log-rank test estimated the rates of overall survival (OS). Multivariate analyses were done by a Cox proportional hazards model. Results The median OS was 14.38 months for the whole cohort. Patients with education ≥9 years, government insurance for civil servants, advanced stage and combination of chemo-radiation treatment had a significantly better OS than their counterparts (p Conclusions Median OS of our cohort was low compared to those reported in international publications, emphasizing the importance to improve the local cancer management. Age, clinical stage and treatment modality were independent favourable predictos for the patients’ OS. Legal entity responsible for the study Ethics committee, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/Dr Sardjito Hospital. Funding Indonesian Society for Hematology and Medical Oncology Yogyakarta Branch; Dutch Cancer Society. Disclosure All authors have declared no conflicts of interest.

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

The uncommon ear tumor of middle ear squamous cell carcinoma (MESCC) is thought to be associated with the history of long-term chronic otitis media in the most cases. The main etiologic factor of MESCC is still unclear and may be multifactorial. Infections of Epstein-Barr virus (EBV) and Human Papillomavirus (HPV) are considered as one of the etiologic factor of MESCC. Previous studies have shown that the EBV and HPV have been detected in MESCC. Although the EBV and HPV have been implicated in human malignancies, their roles in pathogenesis of MESCC have not been elucidated. There has never been report on the presence of EBV and HPV in Indonesian MESCC. This study aimed to determine the presence of EBV and HPV in MESCC. Seven paraffin-embedded tissues of speciment from biopsy were analyzed for the presence of EBV and HPV by immunohistochemistry, stained using polyclonal antibody anti EBNA1 and anti HPV. The samples consisted of 4 (57 %) males and 3 (43 %) females with age range of 26–87 years old. Immunohistochemistry result demonstrated that EBV was detected in three of seven (43 %) and HPV in two of seven (29 %) samples. Coexistence of the presence of EBV and HPV were found in one of seven (14 %) sample. The presence of EBV and HPV in MESCC suggests that viral infection may play an important etiologic role in the carcinogenesis of middle ear.

Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr virus (EBV) antigen complexes, usually involving multiple serological assays, is important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through combination of two synthetic peptides representing immunodominant epitopes of EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from healthy donors ( n = 367), non-NPC head and neck cancer patients ( n = 43), and biopsy-proven NPC patients ( n = 296) of Indonesian and Chinese origin. Higher values of optical density at 450 nm for EBV IgG were observed in NPC patients compared to the healthy EBV carriers, but the large overlap limits its use for NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of 80.1% and 70.9%, whereas combined single-well coating with both peptides yielded sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive and negative predictive values (PPV and NPV, respectively) for the combined EBNA1 plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia panel, the level of EBV IgA reactivity was not associated with NPC tumor size, lymph node involvement, and metastasis stage, sex, and age group. In the China panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and 84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC samples. The use of these combined methods for seroepidemiological screening studies is proposed.

Poor prognosis in nasopharyngeal carcinoma patients may result from resistance to the apoptosis-inducing effect of radio- and/or chemotherapy. Apoptosis depends on proper activation of caspase 3, resulting in cleavage of key proteins like PARP-1. To investigate whether disruption of the apoptosis pathway results in therapy-resistant tumour cells, we investigated whether absence of caspase 3 activation in tumour biopsies of nasopharyngeal carcinoma patients is related to poor clinical outcome. Moreover, we investigated whether absence of caspase 3 activation is related to loss of procaspase 3 expression or expression of the apoptosis regulators p53, bcl-2 and XIAP. We studied 36 Indonesian nasopharyngeal carcinoma patients without evidence of distant metastases who were treated with curative intent by radiotherapy only. Activation of caspase 3 and expression of the different markers were determined using specific antibodies. Levels of caspase 3 activation were determined by quantifying positively staining tumour cells. Nasopharyngeal carcinoma-derived C15 and C17 tumour cells were used as control. Absence of caspase 3 activation was strongly related to a poor clinical response to radiotherapy and to a higher T and N stage, resulting in a particularly poor clinical outcome with regard to progression-free (P

Latar belakang: Meningioma ekstrakranial primer merupakan tumor jinak yang berasal dari lapisan otak, tetapi tidak berhubungan dengan aksis sistem saraf pusat, serta tumor ini jarang sekali ditemukan di ekstrakranial, terutama di rongga hidung dan sinus paranasal. Ekstirpasi bedah secara lengkap merupakan pengobatan utama untuk tumor jinak. Tujuan: Memberikan informasi mengenai diagnosis dan tatalaksana meningioma ekstrakranial primer pada regio sinonasal. Kasus: Kasus langka ini ditemukan pada anak laki-laki usia 11 tahun dengan massa tumor pada hidung dan sinus paranasal. Penatalaksanaannya berupa ekstirpasi massa secara lengkap melalui pendekatan rinotomi lateral sinistra, kemudian dilakukan maksilektomi medial dan etmoidektomi eksternal. Pada pemeriksaan histopatologi didapatkan gambaran meningioma tipe transisional (WHO derajat 1). Pewarnaan imunohistokimia vimentin memberikan hasil positif. Setelah dilakukan operasi tampak deformitas minimal pada hidung luar dan proptosis mata kiri dengan visus dalam batas normal. Metode: Penelusuran bukti kepustakaan menghasilkan 81 jurnal, dan hanya 3 jurnal yang relevan dengan pertanyaan klinis kami. Hasil: Ketiga jurnal tersebut merupakan laporan kasus meningioma ekstrakranial sinonasal anak yang ditatalaksana dengan ekstirpasi total, dan tidak didapati kekambuhan pada pemantauan jangka panjang. Kesimpulan: Meningioma ekstrakranial primer mempunyai prognosis yang baik, dengan tingkat kekambuhan yang rendah bila tumor dapat diekstirpasi secara lengkap. Pada kasus ini telah dilaksanakan ekstirpasi total massa tumor. Kata kunci: Meningioma ekstrakranial primer, rinotomi lateral, maksilektomi medial ABSTRACT Background: The primary extracranial meningiomas are benign tumors that originate from the meningens of the brain, but not related with the central nervous system axis. This kind of tumor is rarely found extracranially, especially in nasal cavity and paranasal sinuses. A complete surgical extirpation is the primary treatment of this benign tumor. Objective: To provide information about the diagnosis and management of primary extracranial meningioma in sinonasal region. Case: This rare case was found in 11-year-old boy with tumor mass in the nose and paranasal sinuses. The patient underwent complete mass extirpation with left lateral rhinotomy approach, followed by medial maxillectomy and external ethmoidectomy. Transitional type meningioma (WHO grade 1) was obtained on histopathological examination. Vimentin immunohistochemical staining gave a positive result. In post-surgery evaluation, there was a minimal nasal deformity and protusion of the left eye with vision within normal limits. Methods: Searching for evidence produced 81 journals, and only three were relevant to our clinical question. Result: These three journals were case reports of pediatric extracranial sinonasal meningioma extirpated by surgery and without recurrence at long term follow up. Conclusion: The primary extracranial meningiomas prognosis were good and the recurrence rate were low if a complete extirpation of the tumor could be performed. In this case, total extirpation of the tumor mass had been conducted. Keywords: Primary extracranial meningioma, external approach extirpation, medial maxillectomy

INTRODUCTION:Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. METHODS:All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. RESULTS:In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18-35) from day of diagnosis. CONCLUSION:The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.

Marine actinomycetes is a group of bacteria that is highly potential in producing novel bioactive compound. It has unique characteristics and is different from other terrestrial ones. Extreme environmental condition is suspected to lead marine actinomycetes produce different types of bioactive compound found previously. The aim of this study was to explore the presence and diversity of NRPS genes in 14 anticancer-producing actinomycetes isolated from marine sediment in Indonesia. PCR amplification and restriction fragment analysis of NRPS genes with Hae III from 14 marine actinomycetes were done to assess the diversity of NRPS genes. Genome mining of one species of marine actinomycetes (strain GMY01) also was employed towards this goal. The result showed that NRPS gene sequence diversity in 14 marine actinomycetes could be divided into 4 groups based on NRPS gene restriction patterns. Analysis of 16S rRNA gene sequences of representatives from each group showed that all isolates belong to genus of Streptomyces . Genome mining result showed that strain GMY01 harboring 10 different NRPS gene clusters that encode secondary metabolites, as pure NRPS or hybrid between NRPS and other compounds. These results indicated that marine actinomycetes having a high potential to be developed as source of anticancer drugs development.

Latar belakang: Terapi karsinoma nasofaring (KNF) yang adekuat dan efektif tidak selalu tercapaidi negara berkembang. Ketersediaan alat radioterapi yang tidak seimbang dengan jumlah penderita KNFmenyebabkan keterlambatan jadwal terapi, sehingga berakibat pada buruknya hasil terapi. Alternatifterapi lain perlu dikembangkan untuk mengatasi permasalahan tersebut. Photodynamic therapy (PDT)telah digunakan untuk terapi tambahan pada berbagai kanker, termasuk KNF residu maupun rekuren.Tujuan: Mengetahui respon terapi lokal dan angka harapan hidup 5 tahun penderita KNF residu ataurekuren yang mendapatkan PDT.Metode: Kohort retrospektif dengan data rekam medis penderita KNFresidu atau rekuren yang mendapatkan PDT di Departemen THT-KL RSUP Dr. Sardjito Yogyakarta tahun2005–2011.Hasil: Local response rate sebesar 83,9% dan angka harapan hidup 5 tahun penderita sebesar60,7%. Angka harapan hidup 5 tahun penderita laki-laki lebih tinggi (73,5%) dibandingkan penderitaperempuan (42,2%), perbedaan ini bermakna secara statistik (p=0,045). Angka harapan hidup 5 tahunpenderita berusia 40 tahun (53,0%),meskipun tidak signifikan (p=0,417). Angka harapan hidup penderita yang masih terdapat tumor padanasofaring lebih baik (80%) dibandingkan penderita dengan hasil biopsi nasofaring negatif (57,8%),namun tidak signifikan (p=0,638). Angka harapan hidup penderita berdasarkan stadium saat ditegakkandiagnosis KNF, penderita stadium awal mempunyai angka harapan hidup lebih kecil (53,3%) dibandingkanpenderita stadium lanjut (62,1%), meskipun tidak signifikan (p=0,521).Kesimpulan: Local responserate PDT 83,9% dan angka harapan hidup 5 tahun sebesar 60,7%. PDT merupakan modalitas terapi yangefektif untuk KNF residu maupun rekuren. Kata kunci: Karsinoma nasofaring, photodynamic therapy, angka harapan hidup ABSTRACTBackground: Adequate and effective nasopharyngeal carcinoma (NPC) treatment cannot bereached in developing countries. The lack of radiotherapy apparatus cause delayed treatment thatbring about bad treatment results. An alternative treatment modality should be created to overcome theproblem. Photodynamic therapy (PDT) has been conducted for many malignancies including recurrentor residual NPC. Purpose: To find out the local response rate and 5-year overall survival amongrecurrent or residual NPC patients who got PDT. Method: Retrospective cohort, data was taken frommedical records of patients with PDT in ENT-H&N Surgery Department Sardjito Hospital since 2005until 2011. Results: Local response rate was 83.9%. Five-year overall survival was 6.7%. The 5-yearoverall survival among men was significantly higher than women (73.5%:42.2%) p=0.045. The 5-yearoverall survival among patients 40 years old (76.2%:53.0%)even though it was not significant (p=0.417). The 5-year overall survival among patients with tumor washigher than patients without tumor (80%:57.8%) although it was not significant (p=0.638). The 5-yearoverall survival among patients with previous early stage NPC was lower than previous advanced stage (53.3%:62.1%) although it was not significant (p=0.521). Conclusion: Local response rate of PDT was83.9% and the 5-year overall survival was 60.7%. PDT was found as an effective treatment modalityfor recurrent or residual NPC. Keywords: Nasopharyngeal carcinoma, photodynamic therapy, 5-year overall survival

Background: Squamous cell carcinoma (SCC) is the most frequent malignancy in the head and neck. The treatment modalities of SCC are surgery followed by chemotherapy and/or radiotherapy, could also chemotherapy and/or radiotherapy without surgery. The gold standard of assessing success in SCC treatment is if there no malignant cells found not only in frozen section tissues, but also in post chemotherapy and/or radiotherapy tissues. Determining the spot of biopsy tissue for malignancy assessment after treatment is not easy. Toluidin Blue (TB) is a staining material, absorbed by intercellular space in epithelial dysplasia, included SCC. To determine the validity of Toluidin Blue as sign of accuracy for biopsy site in SCC post treatment malignancy, which not only for surgically treated cases, but also after chemotherapy and/or radiotherapy without surgical treatment. Method: Diagnostic test study to determine sensitivity test, specificity test, positive predictive value and negative predictive value of TB to detect malignant cells in post treatment head and neck SCC patients. Result : There were 30 samples biopsy material from 30 post treatment SCC patients. Sensitivity test was 83,3%, specificity test: 66,7%, positive predictive value: 79.0%, negative predictive value: 72,7%. Conclusion : TB staining is accurate for determining biopsy spot in post treatment head and neck SCC. Keyword : Validity, toluidin blue, squamous cell carcinoma, post treatment. Abstrak : Latar belakang: Karsinoma sel skuamosa (KSS) merupakan jenis keganasan kepala dan leher yang paling sering dijumpai dibanding keganasan yang lain. KSS kepala leher dapat dilakukan terapi pembedahan diikuti kemoterapi dan/atau radioterapi maupun kemoterapi dan/atau radioterapi tanpa pembedahan. Penentuan keberhasilan radikalitas pengobatan ditandai dengan tidak adanya sisa tumor secara mikroskopis yang diambil pada jaringan pasca kemoradiasi tanpa pembedahan, atau pemeriksaan jaringan secara frozen section . Untuk menentukan apakah pada jaringan masih ada sisa tumor atau sudah bebas tumor secara makroskopis terkadang sulit. Toluidin Blue (TB) adalah zat pewarna yang dapat terserap pada ruang interseluler epitel yang mengalami displasia seperti yang terjadi pada KSS. Tujuan: Menilai validitas pewarnaan TB sebagai petanda ketepatan lokasi biopsi KSS pasca terapi, baik pasca pembedahan, maupun yang diterapi dengan kemoterapi dan/atau radioterapi tanpa pembedahan. Metode: Uji diagnostik untuk menentukan sensitifitas dan spesifitas pewarnaan, nilai duga positif dan nilai duga negatif TB sebagai salah satu petanda ketepatan biopsi KSS pasca terapi KSS kepala-leher. Hasil: Didapatkan 30 sampel penelitian yang berasal dari 26 penderita KSS yang telah dilakukan terapi baik bedah maupun kemoradiasi tanpa bedah. Sensitifitas pewarnaan TB terhadap hasil biopsi pasca terapi 83,3%, spesifitas 66,7%, nilai duga positif 79,0% dan nilai duga negatif 72,7%. Kesimpulan: Pewarnaan TB valid untuk menentukan ketepatan biopsi keganasan KSS kepala dan leher pasca terapi. Kata kunci : Validitas, toluidin blue , karsinoma sel skuamosa, pasca terapi

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is invasive and metastasizes easily. In several Asian countries it is the most commonly found of the head and neck malignancies. Epstein Barr virus (EBV) infection is one of the agents causing NPC, so that expression of LMP1 and LMP2 may affect the outcome of therapy, metastasis, recurrence, and survival of NPC patients. This study aimed to investigate their expression in relation to therapy outcome and survival in a series of Indonesian NPC patients. The methods used were nested case control and Kaplan-Meier survival analysis. Differences in therapy outcome in relation to LMP1 and LMP2 expression were analyzed through chi square statistics. As a result, in post treatment NPC, there was a significant difference in therapy outcome between LMP2+ compared to LMP2⁻ (P = 0.001). There was also a significant difference in 24-months-survival between NPCs expressing LMP1+ or LMP2+ compared to those expressing LMP1⁻ or LMP2⁻.

Latar belakang: Karsinoma Nasofaring (KNF) adalah keganasan dengan distribusi etnis dan geografis yang khas. KNF memiliki karakteristik yang berbeda dari kanker kepala dan leher lainnya,seperti perilaku pertumbuhan yang cepat, kecenderungan yang tinggi untuk bermetastasis ke kelenjargetah bening (KGB) regional dan organ jauh. E-cadherin memainkan peran penting dalam pemeliharaanadhesiantar sel-sel epitel. Perubahan molekul adhesi sel E-cadherin yang dimediasi oleh sel-sel kankerberkontribusi untuk peningkatan penyebaran sel tumor dan pembentukan metastasis. Tujuan: Untukmengetahui perbedaan ekspresi E-cadherin pada KNF yang telah bermetastasis dengan KNF yang belumbermetastasis. Metode: Desain penelitian adalah studi kasus-kontrol. Subjek penelitian adalah blok parafindari pasien KNF yang telah menjalani biopsi. Blok dari pasien KNF yang telah bermetastasis dikategorikansebagai kelompok kasus, sementara yang tidak bermetastasis sebagai kelompok kontrol. Sampel dari keduakelompok diperiksa dengan metode imunohistokimia (IHK) menggunakan antibodi E-cadherin. Hasil: Sampel 48 blok parafin, masing-masing kelompok terdiri dari 24 blok. Terdapat perbedaan yang signifikanekspresi E-cadherin dengan p

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

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and is strongly associated with Epstein-Barr virus (EBV). We investigated the primary diagnostic value of circulating EBV DNA and anti-EBV immunoglobulin G (IgG) and IgA levels in Indonesian NPC patients ( n = 149). By a 213-bp Epstein-Barr virus nuclear antigen 1 (EBNA1)-based real-time LightCycler PCR, 72.5% of patients were positive for EBV DNA in whole blood, with 29.5% having levels above a previously determined clinical cutoff value (COV) of 2,000 EBV DNA copies/ml, the upper level in healthy carriers. In a 99-bp LightCycler PCR, 85.9% of patients were positive and 60.4% had levels above the COV. This assay quantified a significantly higher EBV load than the 213-bp PCR assay ( P < 0.0001), suggesting that circulating EBV DNA is fragmented. Using data from 11 different studies, we showed a significant inverse correlation between PCR amplicon size and the percentage of patients positive for circulating EBV DNA (Spearman's rho = −0.91; P < 0.0001). EBV DNA loads were unrelated to anti-EBV IgG or IgA levels, as measured by VCA-p18 and EBNA1-specific synthetic peptide-based enzyme-linked immunosorbent assays. The presence of circulating tumor cells was assessed by amplification of BamHI-A rightward frame 1 (BARF1) mRNA, a viral oncogene abundantly expressed in EBV-carrying carcinomas but virtually absent from EBV-associated lymphomas. Despite high EBV DNA loads and the presence of EBNA1 and human U1A small nuclear ribonucleoprotein mRNA, BARF1 mRNA was never detected in blood. We conclude that amplicon size significantly influences EBV DNA load measurement in NPC patients. The circulating EBV DNA load is independent of serological parameters and does not reflect intact tumor cells. The primary diagnostic value of the EBV DNA load for the detection of NPC is limited.

Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal carcinoma (NPC) and control subjects, by use of immunofluorescence assay (IFA). Control donors (n=150) showed IgG responses to few EBV proteins--VCA-p18, VCA-p40, EBNA1, and Zebra--and sporadically weak IgA reactivity to EBNA1 and VCA-p18. Patients with NPC stage 1 (n=6) had similar response patterns. Patients with NPC stage 2-4 (n=132) showed significantly more diverse IgG and IgA responses to EA and VCA proteins--VCA-p18/-p40, EBNA1, Z-encoded broadly reactive activator, and EAd-p47/54, -DNAse, -thymidine kinase, and -p138. No correlation was found between IFA titers and the number of EBV proteins recognized by IgG or IgA. Our results reveal dissimilarity between EBV polypeptides recognized by IgG and IgA antibodies, which suggests independent B cell triggering events.

Local treatment of residual or recurrent nasopharyngeal carcinoma (NPC) is a challenge. Photodynamic therapy (PDT) is an established treatment modality for incurable head and neck carcinoma. Several studies reported induction of an immune response after PDT. We present a patient with residual T4N0M0 NPC who was treated with PDT for residual disease after initial treatment with neo-adjuvant chemotherapy and radiotherapy. Five years after PDT, the tumor did not progress and the patient is still in good condition. We discuss this remarkable long-term response to PDT and speculate on possible mechanisms.

Aim: Epstein-Barr virus (EBV) infection and family history are strong risk factors associated with undifferentiated nasopharyngeal carcinoma (NPC). The presence of aberrant immunoglobulin A (IgA) antibodies against specific EBV antigens in healthy individuals can be predictive of the disease. Unlike in familial NPC, very limited reports have explored the EBV IgA antibody presence within families of sporadic cases of NPC.The aim of this study is to determine whether EBV IgA was more frequently observed among healthy family members of sporadic cases of NPC compared to healthy non-family individuals. Methods: First-degree relatives of NPC patients (n = 508) were recruited in a home visite program. Non-family individuals (n= 284) were recruited from Yogyakarta blood bank. Sera from all individuals were tested in standardized peptide-based EBV IgA ELISA and a positive result of seroreactivity was defined as OD450 >0.354, being the cutt-of value (CoV). Data on demographic variables were collected using a questionnaire through face-to-face interviews. Results: A total of 280 (35.4%) individuals showed seroreactivity of EBV IgA. A significant higher frequency was observed in the first-degree relatives of NPC cases than in non-family individuals (41.9% versus 21.2%, p Conclusions: Family members of NPC cases demonstrated higher level of EBV IgA seroreactivity compared to non-family individuals, implicating a suitability of screening program among this group. Disclosure: All authors have declared no conflicts of interest.

Background Overexpression of excision repair cross complementation group 1 (ERCC1) has been reported to be associated with resistance to platinum-based chemotherapy in head and neck cancer. Since cisplatin-based adjuvant chemoradiotherapy is the standard treatment for nasopharyngeal cancer (NPC) in Indonesia, it is important to investigate the role of ERCC1 as a possible predictive marker of disease progression in our patients. Methods Consecutive samples obtained from our pathology archives of NPC from 31 patients who were receiving standard treatment with cisplatin-based chemoradiotherapy were examined for ERCC1 expression by use of immunohistochemistry. A retrospective cohort study was done and overall survival curves (OS) were plotted versus expression of ERCC1. Findings ERCC1 expression was high in 16 (51.6%) patients and low in 15 (48.4%). There were no differences in the baseline characteristics between the two groups (age, sex, and stage of the disease; p > 0.05). Median survival was 15.5 months. Analysis of OS showed a significant difference between the two groups ( p = 0.02). A univariate analysis of the baseline characteristics and ERCC1 in relation to the 1 year OS showed that only ERCC1 was significant. 53.3% (95% confidence interval (CI) 40.4–66.2) of patients in the group with high ERCC1 expression had an OS of 1 year or more, whereas 80% (95% CI 69.7–90.3; p = 0.02) of the group with low ERCC1 expression had an OS of 1 year or more. The median 1 year OS in the high ERCC-1 group was 13.2 months (95% CI 0.0–27.2), whereas it was not achievable in the low ERCC-1 group. Hazard ratio for the group with high expression of ERCC1 was 3.304 (95% CI 1.12–9.71). Interpretation The low expression of ERCC1 might prolong the overall survival in Indonesian patients with NPC who are receiving standard cisplatin-based chemoradiotherapy. The authors declared no conflicts of interest.

Background: Nasopharyngeal carcinoma (NPC), especially the WHO type III, is correlated almost100% with Epstein Barr Virus (EBV) infection. This is indicated by high IgG and IgA antibody responsesagainst viral capsid antigen (VCA), early antigen (EA) and Epstein Barr Nuclear antigen (EBNA).Increased IgA NPC character antibodies may be detected 2-10 years before the presence of the tumor. Thisoccurs as a result of reactivation of EBV infection. Purpose: To find out the level of IgA NPC characterantibodies (EBNA1+VCA p-18) in patients with chronic symptoms in the head and neck and to determine whether the level of IgA can be used as an early sign of NPC. Methods: Observational analytic study on 218 patients with chronic symptoms in the head and neck. The research was conducted from July 2006to September 2010. ELISA technique was used as serology test for IgA (EBNA1+VCA p-18). Result: Samples were 90 males and 128 females. High level of IgA by ELISA was found in 28 males (31.1%) and 45 females (35.2%). The IgA level tended to increase with age. The most common chronic symptoms inthe head and neck were chronic rhinitis (15.6%) and nasal obstruction (7.8%). From all patients who hadhigh level of IgA, 3 patients (4.1%) were found positive of early stage NPC. Conclusion: More than 33%of patients with chronic symptoms of head and neck had high level of IgA NPC character. This methodcan be used as an early detection of NPC. Keywords: serology test in NPC , EBNA1, VCA p-18, NPC symptoms in head and neck Abstrak : Latar belakang: Karsinoma nasofaring (KNF) terutama tipe WHO III berkorelasi hampir 100%dengan infeksi Epstein Barr Virus (EBV). Hal ini ditunjukkan dengan tingginya respons antibodi IgGdan IgA terhadap viral capsid antigen (VCA), early antigen (EA) EBV serta antibodi Epstein BarrNuclear Antigen (EBNA). Kenaikan antibodi IgA dengan karakter KNF dapat terjadi 2-10 tahun sebelumterjadinya tumor. Hal ini terjadi sebagai akibat adanya reaktivasi infeksi EBV. Tujuan: Mengetahui kadarIgA karakter KNF (EBNA1+VCA p-18) pada penderita dengan gejala kronis di daerah kepala dan leherdan mengetahui apakah kadar IgA dapat digunakan sebagai tanda awal terjadinya KNF. Metode: Suatukajian analitik observasional terhadap 218 penderita dengan gejala kronis di daerah kepala dan leher.Penelitian ini dilakukan Juli 2006 sampai dengan September 2010. Pemeriksaan serologi IgA (EBNA1+VCA-p18)dilakukan denganteknik ELISA. Hasil: Terdapat90penderita laki-lakidan128 penderitaperempuan.HasiltesserologiIgAELISAdengankadartinggiditemukanpada28laki-laki(31,1%)dan45perempuan (35,2%). Kadar IgA cenderung meningkat pada peningkatan usia. Gejala kronis yangterbanyak dikeluhkan penderita adalah rinitis kronis, yaitu sebanyak 34 penderita (15,6%), diikuti denganobstruksi hidung sebanyak 17 penderita (7,8%). Pemeriksaan klinis lebih lanjut dari penderita yangmempunyai kadar IgA tinggi menunjukkan bahwa 3 penderita (4,1%) positif terkena kanker nasofaringstadium awal. __ Lebih dari 33% penderita dengan gejala kronis di daerah kepala dan lehermemiliki kadar IgA karakter KNF yang tinggi. Kadar IgA karakter KNF yang tinggi dapat digunakansebagai penanda awal kejadian KNF. Kata kunci: uji serologi KNF,EBNA1, VCA p-18, gejala KNF

Background: Nasopharyngeal carcinoma (NPC) is one of the most common among head and neck malignancies, especially in some Asian countries. Epstein-Barr Virus (EBV) is one of the agent causing NPC, expressing many proteins such as Epstein-Barr nucleus antigen (EBNA). Expression of EBNA theoretically influencing therapy KNF outcome. Purpose: To differentiate therapy result between NPC expressed positive EBNA1 and EBNA2 compared with NPC expressed negative EBNA1 and EBNA2. Method: Nested case control study toward 28 complete remission NPC patients and 28 partial remission NPC patients post treatment. Result: There was no significant difference in therapy outcome between NPC with EBNA1 expression =4.90 compared to EBNA1

5577 Background : Combination of GC chemotherapy is active and has a favorable safety profile in some several solid tumors, including advanced squamous cell head and neck cancers. We evaluated the efficacy and toxicity of this combination in advanced or recurrent NPC. Methods : In a two-center phase II study, patients with histologically confirmed advanced or recurrent NPC, measurable disease, WHO PS 0–2, age 19–70 years, adequate organ function, and written informed consent, were treated with Gemcitabine 1250 mg/m2 day 1 and day 8; Cisplatin 80 mg/m2 day 1 every 3 weeks. Primary endpoint was objective response rate. Results : Thirty five patients were enrolled between 12/01 and 11/03. There were 27 male and 8 female, 33 with Javanese ethnicity and 2 Caucasian;. with a mean age was 45 years (19–68). All but 3 patients (91.4%) had undifferentiated histology. Twenty-two patients had metastatic or recurrent disease, 13 patients had locally advanced disease. All patients were chemonaive, and 10 patients had r...

BackgroundTreating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC.MethodIn this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10 mm. Foscan® 0.15 mg/kg was administered intravenously. After 96 h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis.ResultsTwenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed.ConclusionThis study showed that PDT is effective in treating local failures of NPC with a depth of less than 10 mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.