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PURPOSEChemotherapy-induced peripheral neuropathy (CIPN) poses a substantial challenge in breast cancer (BC) chemotherapy, affecting the patient's quality of life. Recent studies have focused on exploring predictors and patterns of CIPN occurrence. We aimed to develop a prediction model for CIPN occurrence using a classification and regression tree (CART) algorithm.METHODSIn this prospective study of 170 patients with BC undergoing chemotherapy, patient-reported adaptation of the Common Terminology Criteria for Adverse Events version 4.0 was used to assess CIPN occurrence. Multivariable analysis using the CART model was tuned using 10-fold cross-validation to identify baseline predictors for CIPN throughout chemotherapy. A receiver operating characteristic curve analysis was conducted for the CART model. A multivariable logistic regression was conducted from the variables included in the CART model to assess the strength and direction of the association.RESULTSThe prevalence of CIPN was 64.7% (n = 110). The most decisive predictor of CIPN occurrence in the CART model was the subject's C-reactive protein (CRP) level. CRP level >3.91 mg/dL, BMI >21.85 kg/m2, and a marital status of unmarried have predicted a probability of 100% in CIPN occurrence. The CART model showed an accuracy of 65.9%, sensitivity of 51.7%, specificity of 73.2%, and an area under the curve of 0.705. A CRP level of >3.91 mg/dL and a neutrophil-to-lymphocyte ratio (NLR) of >2.82 are significantly associated with the occurrence of CIPN (odds ratio [OR], 2.01 [95% CI, 1.01 to 4.01]; P = .046, OR, 2.09 [95%, CI, 1.02 to 4.24]; P = .042, respectively).CONCLUSIONBaseline CRP, NLR, BMI level, and marital status are significant predictors of CIPN occurrence throughout chemotherapy. Our CART model was better at ruling out individuals who would not experience CIPN. The CART model may provide insight into the future development of individualized patient care and prevention strategies.

PURPOSEThere has been a global increase in early-onset colorectal cancer (EOCRC), yet there has been very limited exploration of its impact in Indonesia. This study aimed to determine the clinicopathologic characteristics and the overall survival (OS) of EOCRC compared with those of average-onset colorectal cancer (AOCRC).METHODSMedical records were retrospectively reviewed from all patients presenting with colorectal cancer (CRC) at Dr Sardjito General Hospital (Yogyakarta, Indonesia) between 2016 and 2019. Sociodemographic, clinicopathologic, and treatment variables were extracted. t Tests were used to compare characteristics of EOCRC and AOCRC patient groups. The Cox proportional hazards regression model was used to analyze age and other potential prognostic factors.RESULTSThe total population (N = 1,276) comprised EOCRC (n = 149; 11.7%) and AOCRC (n = 1,127; 88.3%) patients. EOCRC patients were more likely to have a higher education level, be single, have out-of-pocket insurance, be underweight, and have signet ring histology (all P values

Objectives: To assess the feasibility, acceptability, and preliminary effectiveness of implementing a home-based aerobic and resistance exercise for patients with breast cancer receiving endocrine treatment in Indonesia. Methods: This is a mixed methods study with concurrent design consisting of quantitative single-arm pre-post intervention and qualitative study. We recruited patients with breast cancer ( N = 36) receiving endocrine treatment and assigned 12 weeks of home-based pedometer-driven walking and resistance exercises using therapeutic bands. Descriptive statistics were used to assess the feasibility (recruitment, retention, and adherence) and safety. The modified Bruce treadmill test was used to measure predicted aerobic capacity ( V̇O 2 peak). Quality of life and fatigue were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and fatigue severity scale. Measurements were performed at baseline and post-intervention and analyzed with the paired t -test or Wilcoxon test. Semi-structured interviews and thematic analysis were conducted post-intervention to explore patients’ acceptability. Results: The results showed a recruitment rate of 75%, retention rate of 89%, and adherence rates were 53% for aerobic and 78% for resistance exercise. No severe adverse events were reported. Post-intervention interviews identified positive attitudes toward the intervention, with low burden and high perceived benefit. Exercise duration and predicted V̇ O 2 peak increased significantly (+1.1 min, p = 0.001 and +2.3 ml/kg/min, p = 0.043), but no significant change was detected for Quality of Life ( p > 0.050) or fatigue severity ( p = 0.299). Conclusions: A home-based aerobic and resistance exercise was feasible when implemented in the context of routine care in our study population, improving predicted aerobic capacity. Further research is required to understand limited changes to Quality of Life and fatigue and adaptations to support implementation in additional sites in Indonesia.

Introduction: Little is known about Indonesian metastatic CRC patients’ survival and prognostic factors, although this malignancy is one the most frequent cancer in the country. We aimed to investigate the survival outcome and the factors influencing local CRC patients presenting with a metastatic stage at diagnosis. Methods: A retrospective cohort study was done on 441 data of synchronous metastatic CRC cases treated between January 2016 and December 2019 at Dr. Sardjito Hospital, Yogyakarta, Indonesia. Secondary data were collected from the CRC clinical registry database. Demographic, clinicopathology and the type of treatment were collected. Survival staus was obtained from the registry database and communication to patients or caring families. Kaplan-Meier curves were used to estimate the overall survival (O.S). The Cox proportional hazards regression mode was applied to analyzethe potential factors affecting survival. Results: The median follow up of the recent study was 17 months, The median overall survival was 13 months. Two-year overall survival was 37% and the estimated 5-year overall survival was 16.1%. Multivariate cox analyses identified poor performance status (HR 2.639, 95% CI 1.438-4.842, p = 0.002), elevated carcinoembryonic antigen (CEA) (HR 2.795, 95% CI 1.509-5.176, p = 0.001) and higher histological grade (HR 2.019, 95% CI 1.112-3.667, p = 0.021) were associated with poorer overall. Conclusion: Poor performance status, high CEA level, and higher histological grade as factors that were associated with unfavourable overall survival of patients with synchronous metastatic colorectal cancer in Yogyakarta, Indonesia.

Malaria is known to be a significant risk factor and also a potential complicating factor during the treatment of lymphoid malignancy. There has not been a reported case of malaria reactivation that occurred weeks after cytotoxic chemotherapy completion, especially in non-endemic regions. Our patient was a 47-year-old man with a history of repeated falciparum malaria infection experiencing 2 months of progressive unilateral nasal blockage and recurrent anterior epistaxis, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) through pathological examination. He was treated with six cycles of classical R-CHOP, resulting in complete remission. One month after remission, he experienced shivering, fever, sweating, and a return to normal temperature, which repeated irregularly for roughly 1 week. His laboratory result showed anaemia, leucopenia, and profound thrombocytopenia. Immunochromatographic testing (ICT) confirmed the diagnosis of falciparum malaria. This case was considered a relapse since our centre is not in the malaria-endemic region. He was cured with a combination of dihydroartemisinin-piperaquine and primaquine. Our case demonstrated the duality of malaria as potential aetiology and treatment complicating factor in DLBCL.

ObjectivesColon and rectal cancer are associated with different risk factors and prognostic. However, this discrepancy has not been widely explored in the local population. This study aimed to investigate the site-specific likelihood of colorectal cancer (CRC) incidence in the Yogyakarta province, Indonesia.MethodsThis cross-sectional study analyses 1,295 CRC cases diagnosed in 2008-2019 registered in the Yogyakarta population-based cancer registry (PBCR) database. Cases were grouped into colon and rectal cancer. Log-binomial regression was used to determine the relative risk of either colon or rectal cancer across different gender, age group, and rurality of residence. The age-specific rates were calculated by age group and temporal trend for each group were analyzed using joinpoint regression.ResultsFemales displayed higher odds of colon cancer (relative risk/RR = 1.20, 95%CI = 1.02-1.41) and lower odds of rectal cancer (RR = 0.92, 95%CI = 0.85-0.99). Elevated odds of colon cancer were observed in younger age group, especially 30-39 (RR = 1.87, 95%CI = 1.10-3.19), while decreased odds of rectal cancer was apparent in age group 30-39 and 40-49 (RR = 0.75, 95%CI = 0.60-0.93 and RR = 0.82, 95%CI = 0.69-0.98, respectively). Living in urban or rural areas did not significantly influence the odds of either having colon (RR = 0.98, 95%CI = 0.82-1.17) or rectal cancer (RR = 1.01, 95%CI = 0.93-1.10). During 2008-2019, trends of colon cancer in age ConclusionsYogyakarta population shows higher odds of young-onset colon cancer, especially between age 30-39 years old. Overall observation of trend shows increasing incidence in young-onset colon cancer, and non-significant decrease in rectal cancer.

Adrenal insufficiency in systemic lupus erythematosus is rarely detected, especially in male patients. Nevertheless, such coexistence can occur, and screening for systemic lupus erythematosus should be considered in primary adrenal insufficiency with symptoms of systemic multiorgan involvement. We report a 22-year-old Asian man, initially diagnosed with bicytopenia, developed severe unintentional weight loss, skin and mucosal hyperpigmentation, along with persistent fatigue. Laboratory examination showed positive antinuclear antibody—indirect immunofluorescence, elevated anti-double-stranded DNA, extremely low morning serum cortisol, and mildly elevated thyroid stimulating hormone with normal free T4. He was diagnosed with systemic lupus erythematosus, manifesting as chronic primary adrenal insufficiency, subclinical hypothyroidism, and bicytopenia. He was treated with mycophenolic acid of 180 mg b.i.d, methylprednisolone of 4 mg q.d, and vitamin D3 1000 IU q.d. Methylprednisolone was given for its anti-inflammatory property and as a simple once-daily regimen to supplement glucocorticoid deficiency. Levothyroxine was not prescribed for our patient since his thyroid stimulating hormone was only mildly elevated, and supplementation of levothyroxine in the setting of adrenal insufficiency might precipitate an adrenal crisis. At the 6-month follow-up, he was no longer fatigued, he regained his body weight, his skin and mucosal hyperpigmentation improved significantly, his thyroid stimulating hormone level normalized (without levothyroxine supplementation), and his complete blood count stabilized, remitting him from the need for transfusion.

We aimed to explore the district-level temporal dynamics and sub-district level geographical variations of colorectal cancer (CRC) incidence in the Special Region of Yogyakarta Province. We performed a cross-sectional study using data from the Yogyakarta population-based cancer registry (PBCR) comprised of 1,593 CRC cases diagnosed in 2008-2019. The age-standardized rates (ASRs) were determined using 2014 population data. The temporal trend and geographical distribution of cases were analysed using joinpoint regression and Moran’s I statistics. During 2008-2019, CRC incidence increased by 13.44% annually. Joinpoints were identified in 2014 and 2017, which were also the periods when annual percentage change (APC) was the highest throughout the observation periods (18.84). Significant APC changes were observed in all districts, with the highest in Kota Yogyakarta (15.57). The ASR of CRC incidence per 100,000 person- years was 7.03 in Sleman, 9.20 in Kota Yogyakarta, and 7.07 in Bantul district. We found a regional variation of CRC ASR with a concentrated pattern of hotspots in the central sub-districts of the catchment areas and a significant positive spatial autocorrelation of CRC incidence rates in the province (I=0.581, p

Introduction: Limited research exists exploring the experience of living with advanced breast cancer in Indonesia. We sought to explore the narratives of women with breast cancer across the illness trajectory to understand their experiences from diagnosis to accessing and undergoing cancer treatments to inform the development of cancer care. Methods: A nested, exploratory study adopting a qualitative approach. We conducted in-depth face-to-face interviews with women living with advanced breast cancer in Yogyakarta, Indonesia. We purposively sampled participants by age, education and marital status. All interviews were transcribed verbatim with thematic analysis used to identify, analyse and report patterns and themes within the data. Findings: Four main themes were derived: 1) Early experiences, prior to accessing health care; 2) Navigating the system to access treatment; 3) Enduring chemotherapy and advancing disease, with crucial family support; 4) Seeking normalcy and belief in treatment. From initial symptoms through to undergoing treatments, the experience of participants was punctuated by barriers and challenges. Discussion: Presentation delays were driven by dismissing initial symptoms, seeking alternative medicines, and fear of surgery. Access to healthcare required participants to contend with long-distance travel to facilities, tiered and convoluted referral processes, and adverse effects and financial impact of treatments. Individual determination, belief in God, and the role of families were critical throughout the disease trajectory. Adopting a focus across the disease trajectory facilitated the identification of enduring and persistent challenges to care delivery that can inform targeted development and optimisation of care delivery for women with breast cancer.

Background: Diffuse Large B-Cell Lymphoma (DLBCL) has been classified based on Cell of Origin (COO) into Germinal Center B-cell (GCB) and Non-Germinal Center B-cell (Non-GCB). The practical application of this concept by immunohistochemistry (IHC)-based subtyping with Hans’ algorithm and its role as a prognostic factor has been widely investigated with conflicting results. Moreover, the recent deeper molecular characterizations of DLBCL have been another challenges for this approach to remain as a prognostic factor. Objective: To determine the prognostic value of COO by IHC-based subtyping with Hans’ algorithm for DLBCL. Materials and Methods: This was a single-center retrospective analysis including DLBCL cases diagnosed in 2014-2019 from Dr. Sardjito Hospital, Yogyakarta, Indonesia. Hans’ algorithm with CD10, BCL6, and MUM1 were used. The two subtypes were compared in terms of clinicopathological features and 3 years overall survival. Results: Seventy patients were included in this study. Non-GCB was predominant than GCB 74.3% vs 25.7%, with the ratio of 2.8:1. No statistical difference in the clinicopathological features from both subtypes in terms of age, gender, Ann Arbor stadium, ECOG performance status, extra-nodal involvement, and LDH level. Ann Arbor stadium and ECOG showed significant prognostic value for patients outcome with multivariate analysis (OR 3.64; 95%CI 0.18-0.61; p=0.001) and (OR 2.68; 95%CI 0.11-0.77; p=0.009). Survival analysis based on COO did not show significant difference between GCB and non-GCB subtypes (log rank=0.46). Further analysis based on COO and the use of rituximab showed better OS in the two subtypes than without rituximab although not significant (log rank=0.67). Conclusion: The role of COO with Hans’ algorithm as prognostic factor in DLBCL is not confirmed in this study. Some related factors may be the addition of rituximab and the recent molecular characterization of DLBCL which covered a more subtle classification of the disease beyond GCB and non-GCB subtypes.

BackgroundBreast cancer is a significant public health concern worldwide, including in Indonesia. Little is known about the spatial and temporal patterns of breast cancer incidence in Indonesia. This study aimed to analyze temporal and spatial variations of breast cancer incidence in Yogyakarta Province, Indonesia.MethodsThe study used breast cancer case data from the Yogyakarta Population-Based Cancer Registry (PBCR) from 2008 to 2019. The catchment areas of the PBCR included the 48 subdistricts of 3 districts (Sleman, Yogyakarta City, and Bantul). Age-standardized incidence rates (ASR) were calculated for each subdistrict. Joinpoint regression was used to detect any significant changes in trends over time. Global Moran's and Local Indicators of Spatial Association (LISA) analyses were performed to identify any spatial clusters or outliers.ResultsThe subdistricts had a median ASR of 41.9, with a range of 15.3-70.4. The majority of cases were diagnosed at a late stage, with Yogyakarta City having the highest proportion of diagnoses at stage 4. The study observed a significant increasing trend in breast cancer incidence over the study period the fastest of which is in Yogyakarta City with an average annual percentage change of 18.77%, with Sleman having an 18.21% and Bantul having 8.94% average changes each year (p ConclusionsWe found significant spatial clustering of BC ASR in the Yogyakarta Province, and there was a trend of increasing ASR across the region. These findings can inform resource allocation for public health efforts to high-risk areas and develop targeted prevention and early detection strategies. Further res is needed to understand the factors driving the observed temporal and spatial patterns of breast cancer incidence in Yogyakarta Province, Indonesia.

Abstract Metastatic breast cancer may present as a pericardial effusion that can progress to a life‐threatening cardiac tamponade. Pericardial window followed by initial chemotherapy needs to be immediately applied in order to achieve a favorable outcome.

PurposeTo investigate factors associated with delays in presentation and diagnosis of women with confirmed breast cancer (BC).MethodsA cross-sectional study nested in an ongoing prospective cohort study of breast cancer patients at Dr Sardjito Hospital, Yogyakarta, Indonesia, was employed. Participants (n = 150) from the main study were recruited, with secondary information on demographic, clinical, and tumor variables collected from the study database. A questionnaire was used to gather data on other socioeconomic variables, herbal consumption, number of healthcare visits, knowledge-attitude-practice of BC, and open-ended questions relating to initial presentation. Presentation delay (time between initial symptom and first consultation) was defined as ≥3 months. Diagnosis delay was defined as ≥1 month between presentation and diagnosis confirmation. Impact on disease stage and determinants of both delays were examined. A Kruskal-Wallis test was used to assess the length and distribution of delays by disease stage. A multivariable logistic regression analysis was conducted to explore the association between delays, cancer stage and factors.ResultsSixty-five (43.3%) patients had a ≥3-month presentation delay and 97 (64.7%) had a diagnosis confirmation by ≥1 month. Both presentation and diagnosis delays increased the risk of being diagnosed with cancer stage III-IV (odds ratio/OR 2.21, 95% CI 0.97-5.01, p = 0.059 and OR 3.03, 95% CI 1.28-7.19, p = 0.012). Visit to providers ≤3 times was significantly attributed to a reduced diagnosis delay (OR 0.15, 95% CI 0.06-0.37, p ConclusionsAlmost half of BC patients in our setting had a delay in presentation and 64.7% experienced a delay in diagnosis. These delays increased the likelihood of presentation with a more advanced stage of disease. Future research is required in Indonesia to explore the feasibility of evidence-based approaches to reducing delays at both levels, including educational interventions to increase awareness of BC symptoms and reducing existing complex and convoluted referral pathways for patients suspected of having cancer.

ObjectivesTo observe pre- and post-treatment vitamin D level and its association with treatment and concomitant factors in breast cancer patients treated with chemotherapy.MethodsWe performed a pre-post observational analysis that nested in an ongoing prospective cohort study of breast cancer patients at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 136 subjects were recruited from the main study. Information on subjects' socio-demographic characteristics clinical status, and tumour profile was assessed at baseline. Number of chemotherapy cycles and chemotherapy-induced nausea vomiting (CINV) were also recorded. Vitamin D concentration was measured using ELISA methods at baseline and post-treatment. Vitamin D level of ResultsThe mean vitamin D level before chemotherapy was very low (8.80±3.64 ng/ml) in the whole panel. Higher AST level were associated with lower vitamin D level at baseline (r = -0.188, p = 0.028). Severe deficiency was found in 82.4% subjects at baseline and the rate increased to 89.0% after chemotherapy. Eighty-five cases showed a decrease level whereas 51 showed a slight improvement. Overall, a significant decrease of the vitamin D level was observed after chemotherapy (median change 3.13±4.03 ng/ml, p 6 cycles of chemotherapy were less likely to experience a decreased level of post-treatment vitamin D (OR = 0.436, 95% CI = 0.196-0.968, p = 0.039).ConclusionsIndonesian breast cancer patients showed pre-existing severe vitamin D deficiency and deterioration of vitamin D after chemotherapy. Future research is needed to explore its implication towards patients' survival in the local setting. Evidence-based approach also needs to be taken to address this modifiable condition, including increasing awareness of the importance of maintaining vitamin D sufficiency both in patients and the general population.

Transient pancytopenia due to reactive bone marrow suppression often occurs in hemophagocytic lymphohistiocytosis (HLH), a syndrome resulting from excessive immune activation following a severe infection. We reported two cases with pancytopenia and disseminated histoplasmosis accompanied by HLH, initially suspected to be blood malignancies. Our first case documented the relevance between the improvement of pancytopenia and the clearance of Histoplasma capsulatum in serial bone marrow aspirations. The second case showed immense Histoplasma engulfment by the macrophage in relation to a severe clinical condition, followed by improvement of clinical symptoms in accordance with the recovery of pancytopenia. These two cases highlighted the importance of comprehensive and critical analysis for cases with concurrent pancytopenia and severe infection, since it may be that the pancytopenia underlies the severe infection or vice versa.

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.

Breast cancer is a type of carcinoma with a high prevalence. The treatment of breast cancer through chemotherapy can cause a risk to healthy cells throughout the body. The neutrophil is one of the cells that is influenced by chemotherapy drugs. Chemotherapy-induced neutropenia is one of the most common toxic effects experienced by patients and often threatens chemotherapy to use efficiency. In this paper, we introduce an interaction model between blood components, i.e., neutrophil, lymphocytes, and albumin, with chemotherapy drugs. The model is important to understand the neutropenia effect due to chemotherapy in mathematical perspective and to calculate breast cancer patients’ survival level. Our model is a four-dimensional system of the first-order ODE with 13-dimensional parameter space. We focus our study for understanding the steady-state conditions and the bifurcations when the parameter values are varied. Here, we also study the role of albumin for reducing the neutropenia effects for breast cancer patients mathematically, where the results can be used as an alternative solution for treating neutropenia in a breast cancer case.

INTRODUCTION: Breast cancer is the most common cancer in women in Indonesia. Patients survival depends on various factors, namely patient-, tumor-, and treatment-related factors. Survival analysis on Indonesian patients has only been reported in a few studies. This study aimed to identify the factors that are associated with five-year overall survival (OS) among patients with breast cancer at a local tertiary hospital in Indonesia. METHODS: A retrospective cohort study was conducted at Dr Sardjito Hospital, Yogyakarta. Female patients diagnosed with breast cancer between January and December 2009 were studied. Socio-demographic and clinicopathological data were collected from the medical and pathological records. The five-year OS rate was assessed using Kaplan Meier method and prognostic factors were analyzed using Cox regression. RESULTS: A total of 213 eligible patients with breast cancer were recruited. The five-year OS probability of the breast cancer patient was 51.07%. The majority of the patients (151, 70.9%) presented an advanced stage at the time of diagnosis. In the bi-variable analysis, cases who were younger, of a lower educational status, at a more advanced stage, with a bigger tumor size, and a central tumor location showed a worse five-year OS compared to their counterparts (p = 0.005, 0.001, 0.004, 0.011, and 0.023, respectively). In the multivariable analysis, age was an independent predictor for the OS (HR = 3.73; 95% CI = 1.0-13.6, p = 0.046). CONCLUSION: The five-year OS of breast cancer patients in the local tertiary hospital was 51.07%. The patients' age at diagnosis was the only significant prognostic factor for the patients' survival.

Background. Colorectal cancer (CRC) is both a global and national burden, being the third most common malignancy in men and the second in women, worldwide. The prognosis of CRC is affected by various factors like the histological grade, angiolymphatic invasion, and distant metastases. Metastasis is an intricate process; one of the possible mechanisms is through the interaction of the chemokines CXCL12 and CXCR4. This study aims to reveal the expression patterns of CXCL12 and CXCR4 in CRC. Methods. The quantitative expressions of CXCL12 and CXCR4 messenger RNA (mRNA) were evaluated in 32 patients with adenocarcinoma-type CRC. Real-time polymerase chain reaction (qRT-PCR) was performed on formalin-fixed tissues. CXCL12 and CXCR4’s expressions, clinicopathologic features, and the treatment response to the CRC were analysed. Results. All tumour tissues showed higher levels of both chemokines compared to normal colonic tissue. The expression of CXCL12 mRNA was higher in rectal location (p=0.04) with a tendency to be higher in later stages (p=0.15), while the expression of CXCR4 was lower in tumours with a lymphatic invasion (p=0.02), compared to their counterparts. There was no difference in the expression of CXCL12 and CXCR4 according to the patients’ ages, gender, tumour differentiation, or response to chemotherapy. Conclusion. Our study demonstrated that the mRNA expression of CXCL12 was significantly correlated with rectal location. CXCR4 mRNA expression was inversely correlated in tumours with a lymphatic invasion.

Epstein-Barr (EBV) infection and presence of a nasopharyngeal cancer (NPC) case in the family increases the risk of developing NPC. Aberrant anti-EBV immunoglobulin A (IgA) antibodies (EBV-IgA) may be present in the sera of non-cancer individuals and predict NPC. Limited studies report the presence of EBV-IgA antibodies within non-cancer individuals in Indonesia where the disease is prevalent. This study aimed at exploring whether EBV-IgA was found more frequently among first degree relatives of NPC patients and individuals presenting with chronic symptoms in the head and neck area compared to healthy controls. A total of 967 non-cancer subjects were recruited, including 509 family members of NPC cases, 196 individuals having chronic complaints in the head and neck region, and 262 healthy donors of the local blood bank. Sera were analyzed using a standardized peptide-based EBV-IgA ELISA. Overall, 61.6% of all individuals had anti-EBV IgA reactivity equal to or below cut off value (CoV). Seroreactivity above CoV was significantly higher in females (38.7%) compared to males (28.7%) (p = 0.001). Older individuals had more seroreactivity above CoV (42.5%) than the younger ones (26.4%) (p< 0.001). Seroprevalence was significantly higher in family members of NPC patients (41.7%), compared to 32.7% of individuals with chronic head and neck problems (p = 0.028) and 16.4% healthy blood donors (p< 0.001). As conclusion, this study showed a significant higher seroprevalence in healthy family members of NPC cases and subjects presenting with chronic symptoms in the head and neck area compared to healthy individuals from the general community. This finding indicates that both groups have elevated risk of developing NPC and may serve as targets for a regional NPC screening program.

Increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. Aiming at developing early diagnostic or prognostic tools for various tumors, we took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and developed a powerful assay based on "multiplex methylation specific-PCR (MMSP)". The MMSP assay was designed to detect tumor-specific methylation status of several NPC-related genes and was capable of acquiring multiplex information simultaneously through a single PCR reaction with the tiny tumor DNA derived from the direct body fluid close to the primary tumor. In this study, we collected paired nasopharyngeal (NP) swabs and NPC biopsies from 49 NPC patients and twenty noncancerous controls. A panel of markers including two EBV, and two cellular TSG markers were applied in this NPC-specific-MMSP assay. We optimized the working condition of MMSP so that it provides information equal to that from the corresponding separate PCRs. The results showed that MMSP patterns of NPC swab were largely consistent with those of corresponding biopsies and significantly distinguished themselves from those of 20 noncancerous volunteers. Among the 69 samples (49 NPCs and 20 normal controls), the sensitivity of detecting NPC from NP swabs is 98%. The specificity is as high as 100%. In conclusion, being characterized by its noninvasiveness, high reproducibility and informativeness, MMSP assay is a reliable and potential diagnostic tool for NPC. It paves the way for the development of population screening and early diagnosis approaches for various tumor types.