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Background Studies to confirm the efficacy and safety of convalescent plasma (CP) as an adjunctive treatment for COVID-19 are still required especially for the countries where standard treatments are unevenly distributed. Methods A non-randomized comparative study was done from June – September 2020 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Plasma with anti-SARS-CoV-2 specific IgG titer of >1:320 were used. Primary end points were clinical and laboratory parameters outcome including BGA, chest X-ray, CT value, CRP, procalcitonin, IL-6, D-Dimer and ALC examined on day 1, 2 and 7 post-transfusion. Results The experimental arm of this study consisted of 15 patients who received CP: 3 (20%) with moderate COVID-19 and 12 (80%) with severe COVID-19. There were 15 historical controls in this study. Ten recipients survived and 5 deceased (survival rate was 66.7%). There were higher rate of pneumonia resolution (OR 1.54, CI95% 0.33–7.23), ARDS resolution (OR 1.20, CI95% 0.25–5.84) and shorter median length of stay (20 vs 22 days, p = 0.41) among recipients compared to controls. Lower mortality rate was observed in recipients vs controls (33.3% vs 46.7% (OR 0.75, CI95% 0.17–3.33)). Median death onset was longer in recipient vs control (7th vs 1st day, p = 0.13). Survival analysis showed protective effect of CP (HR 0.69, CI 95% 0.21–2.27, p = 0.545). Higher CT value improvement (p = 0.51) and negative conversion rate (OR1.20, CI95% 0.25–5.84) were observed in recipients compared to controls. Sub-analysis showed more number of comorbidities, higher procalcitonin and higher D-Dimer among CP recipients who did not survive (p = 0.02 and p = 0.02 respectively). Lower CRP and procalcitonin, and higher ALC were found in survivors compared to non-survivors (p = 0.0437; p = 0.0049; and p = 0.0002 respectively). Conclusion This study showed promising results for CP marked by improvements in clinical outcome, as well as significant reduction of inflammatory markers among recipients.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with dysregulation of somatic hypermutation (SHM) and class switch recombination (CSR) have been known to contribute for its lymphomagenesis. Activation-induced cytidine deaminase (AID) enzyme plays a vital role for both processes. Multiple myeloma oncogene 1 (MUM1) is known to upregulate the AID expression in normal and pathological conditions. However, both AID and MUM1 expression association in DLBCL is still unexplored using immunohistochemistry method. We examined DLBCL samples and then retrospectively tested its correlation with clinical findings. METHODS: A retrospective cohort study with 20 cases of DLBCL biopsy tissue with AID and MUM1 antibody was conducted. The samples were then classified into concordant (AID+/MUM1+ or AID-/MUM1-) and discordant group (AID-/MUM1+). The clinicopathological comparison was performed to observe any association between immunohistochemistry expression and clinical findings. RESULTS: Among 20 samples of DLBCL, concordant expression rate of AID and MUM1 was 80% with kappa Cohen’s of 0.578 ( p =0.004). A significant association was observed between AID and MUM1 expression with a prevalence ratio of 2.25 (95% CI: 1.08-4.67; p =0.008). Clinical characteristics were not significantly different between each group. Restricted mean survival time was shorter in the concordant group compared with the discordant group but statistically insignificant (21.16 vs. 22.5 months; p =0.531). CONCLUSION: The result of this study showed the association between AID and MUM1 expression in DLBCL. However, whether the association may add further molecular heterogeneity of DLBCL is still to be confirmed by expanding the study. KEYWORDS: AID, CSR, DLBCL, MUM1, SHM

Obesity and Metabolic Syndrome have been associated with cardiovascular, diabetes and cancer incidence. Obesity is a state of inflammation. There are cross-talks between adipocyte, adipokines, pro-inflammatory cytokines, insulin, leptin, and other growth factors to initiate signals for proliferation, anti-apoptosis, and angiogenesis. Those networks lead to cancer initiation, promotion, progression, and metastasis. Post menopause women with breast cancer commonly have overweight, obesity, and metabolic syndrome, which are previously reported as conditions to be associated with breast cancer prognosis. MicroRNAs (miRNAs), small non-coding RNA that regulate gene expression, are known to play important roles either in metabolic or carcinogenesis process in patients with breast cancer. Some miRNAs expressions are deregulated in persons either with obesity, breast cancer, or breast cancer with co-morbid obesity. This literature review aimed at reviewing recent publications on the role of obesity, leptin, and microRNA deregulation in adverse prognosis of breast cancer. Understanding the influence of deregulated miRNAs and their target genes in patients with breast cancer and obesity will direct more studies to explore the potential prognostic role of obesity in breast cancer from epigenetic points of view.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype (68.2%) of B cells Non Hodgkin Lymphoma in Indonesia. This tumor heterogeneity is characterized by a variety of clinical conditions, morphology, genetic profiles, therapeutic response, prognosis and survival. Recent studies have shown that CD30 immunohistochemical staining also plays an important role in determining the therapy and prognosis of DLBCL disease. CD30 can also be expressed in DLBCL in approximately 9.5-40%. However, CD30 expression and clinicopathological characteristics of Indonesian DLBCL remain unknown. This study aimed to determine the prevalence of CD30 expression and its correlation with clinicopathological characteristics of Indonesian DLBCL patients. Methods: During a study period of four years, a total of 104 FFPE of DLBCL cases were collected from Anatomical Pathology Department, Sardjito Hospital, Special Region of Yogyakarta, Indonesia. CD30 expression was studied using immunohistochemical techniques (Mouse monoclonal antibody MoAb CD30 cell marque Ber-H2). Correlations between positive CD30 immunoreactivity and clinicopathological characteristics in DLBCL patients were statistically analyzed using chi-square tests. Result: Positivity rate of CD30 expression in 104 DLBCL samples was 13.5% (14/104) using cutoff value of 0% while using a 20% cutoff, it was 1.9% (2/104). Statistical associations of positive CD30 expression and clinicopathological characteristics (age, sex, Ann Arbor stage, extranodal involvement and morphological variants) were not significant (p > 0.05).Conclusions: The prevalence of positive CD30 expression in Indonesian DLBCL patients is 13.5%. There was no statistically significant associations between positive CD30 expression and clinicopathological characteristics.

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.

Ibnu Purwanto,1 Didik Setyo Heriyanto,2 Irianiwati Widodo,2 Mohammad Hakimi,3 Mardiah Suci Hardianti,1 Teguh Aryandono,4 Sofia Mubarika Haryana5 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 3Department of Clinical Epidemiology and Biostatistics Unit, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 4Department of Surgical Oncology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 5Department of Histology and Cell Biology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, IndonesiaCorrespondence: Ibnu PurwantoDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Jalan Farmako, Sekip Utara, Yogyakarta 55281, IndonesiaTel/Fax (+62 274) 560300Email ibnupurwanto@ugm.ac.idPurpose: Determining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC.Patients and Methods: We retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan–Meier curve was used to perform survival analysis.Results: The optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565– 0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66± 1.58 vs 30.23± 1.99; log rank p< 0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3– 29.1) vs 34.3 (31.2– 37.4); p< 0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics.Conclusion: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.Keywords: miR-223, chemotherapy, prognosis, EGFR, TNBC

Coronavirus disease 2019 (COVID-19) has become a world pandemic since early 2020.Currently, there is no established treatment to combat this potentially fatal disease. Convalescent plasma (CP) therapy has a strong scientific basis and historical perspective to treat previous viral infections such as Ebola, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The aim of this review was to evaluate the efficacy and safety of convalescent plasma CP therapy in patients with COVID-19.We searched for every available study from major databases (CENTRAL, MEDLINE via Ovid, EMBASE) through 20th April 2020. We independently screened, extracted, assessed the risk of bias, analyzed the data using SPSS version 26, and narratively summarized the data. For the outcomes, we wanted to evaluate the changes of clinical parameters, radiological appearance, pulmonary function, the titer of neutralizing antibody, viral load, the disappearance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA, and adverse events.We found five case series from our literature searching. The overall methodological quality of the case series was moderate. We included 27 patients, and all patients received CP transfusion. All patients experienced improvement of clinical symptoms and pulmonary lesions after receiving 200 to 2400 mL (median 200 mL) of CP transfusion. All patients in reported studies had negative results of reverse transcriptase-polymerase chain reaction(RT-PCR) after 1 to 26 days of transfusion (median 3 days). There was one non-life threatening adverse event reported after CP transfusion (facial red spot). In conclusion, CP therapy in COVID-19 patients showed promising results as it improved clinical symptoms and parameters, and it is well-tolerated based on our included studies. However, further expanded clinical trials with better designs are still required to evaluate the efficacy of this treatment although suchidea will be quite challenging to be conducted in the era of an epidemic.

Nasopharyngeal Carcinoma (NPC) is a cancer that occurs in nasopharynx which is associated with Epstein-Barr Virus (EBV). Mutation agents in nasopharyngeal neoplasms occur because of EBV infection. Transformation of B-cells due to EBV causes hormone imbalance in lymphoid cells or nasopharyngeal epithelial tissue. Rates of EBV infection have been shown to be prognostic to NPC. The basic level of EBV DNA can be used for stratification prognosis, with higher titers showing greater disease severity and worse outcomes. With mathematical models, there is a correlation between the increase in Epstein-Barr Virus and the increase in Invasive Carcinoma Cells or increase in Nasopharyngeal Carcinoma Cells.

Lymphadenopathy is a non-specific enlargement of lymph nodes which may be caused by infection, cancer, or autoimmune disease. To date, only a few studies reported the diagnostic value of fine-needle aspiration biopsy (FNAB) in lymphadenopathy. This study was performed to evaluate diagnostic reliability of FNAB for benign and malignant lymphadenopathy. This was a retrospective cross-sectional study. The obtained data were statistically analyzed for its sensitivity, specificity, and accuracy. Out of 126 collected FNAB cases with histopathological confirmed results in Dr. Sardjito General Hospital, Yogyakarta, 85 (67.4%) were malignant lymphadenopathy, consisting of 42 metastatic tumor cases, 38 non-Hodgkin lymphoma (NHL) cases, and 4 Hodgkin lymphoma (HL) cases.The overall diagnostic sensitivity, specificity, and accuracy of FNAB in lymphadenopathy was 85.88, 70.73, and 80.95%, respectively. In diagnosing metastatic tumors, FNAB had sensitivity of 83.33%; specificity of 89.28%; and accuracy of 87.3%. The sensitivity, specificity, and accuracy of FNAB in diagnosing NHL was 60.52, 94.31, and 84.12%, respectively. FNAB had a sensitivity of 25%, specificity of 95,90%, and accuracy of 93.65% to diagnose HL. Meanwhile, the accuracy of FNAB in diagnosing malignancies in generalized lymphadenopathy, head-neck lymphadenopathy, and inguinal lymphadenopathy was 90.90; 81.39 and 44.44%, respectively. In conclusion,FNAB has moderate diagnostic value in diagnosing overall malignant lymphadenopathy, including metastatic tumors. FNAB also has some limitations in diagnosing NHL and HL, with sensitivity less than 70% for both diseases. However, it has high accuracy to diagnose generalized lymphadenopathy.

Purpose Long-term estrogen inhibition may cause fatty liver disease (non-alcoholic fatty liver disease; NAFLD) among other adverse conditions such as osteoporosis, climacteric symptoms, thromboembolism, dyslipidemia, and metabolic syndrome. The prevalence of NAFLD among breast cancer patients ranges from 2.3%–45.2%. This study aimed to determine the risk factors for newly developed NAFLD among breast cancer patients after hormonal treatment and whether it influences survival outcomes. Methods This retrospective study investigated hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−), nonmetastatic breast cancer patients diagnosed between January 2010 and December 2018. All patients received adjuvant hormonal treatment for at least 6 months. Clinical data on metabolic profile indicators such as body mass index (BMI), waist circumference, serum cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), diabetes, and presence of metabolic syndrome (MetS) were collected. In total, 160 eligible patients with complete covariate data and survival follow-up were included. Results NAFLD was diagnosed in 35% of patients. There were significant associations of being overweight (BMI ≥ 25 kg/m2), waist circumference > 80 cm, triglycerides ≥ 150 mg/dL, HDL-C ≤ 50 mg/dL, LDL-C < 150 mg/dL, and presence of MetS with the development of NAFLD. However, unlike other factors, MetS and HDL-C were not independently associated with NAFLD. Patients with breast cancer who developed NAFLD had longer disease-free survival (DFS). The median DFS was not reached in the NAFLD group, whereas it was 59.3 (45.6–73.0) months in the non-NAFLD group. No worsening of overall survival was observed in patients with breast cancer and NAFLD. Conclusion The development of NAFLD during treatment in patients with HR+/HER2− breast cancer was associated with several independent risk factors: being overweight, waist circumference, triglycerides, and LDL-C. Interestingly, breast cancer patients with NAFLD during treatment had longer DFS than those without NAFLD.

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.

A rising number of long-term survivors and potential long-term outcome related to the treatment is one of the most important issue due to the advances of management in cancer. The development of secondary malignancy has been reported in a number of cohorts. We present a case of breast cancer patient developing acute myeloid leukemia (AML)- M5 within a relatively short interval of two and a half years from her primary treatment with adjuvant chemotherapy with 4 cycles of doxorubicin and cyclophosphamide, followed by 4 cycles of three weekly paclitaxel (AC-T) and radiotherapy. What could be attributed to the occurrence of secondary leukemia in this patient will be discussed.

Mathematical modeling of Ebsteins-Barr Virus (EBV) infection on nasopharynx cancer could predict theoretically the changes of healthy cell into invasive carcinoma. It would be very useful, especially for determining the right strategy to suppress the mortality rate due to nasopharynx cancer. Mathematical modeling use Tumorigenesis Model for EBV-associated Nasopharyngeal Carcinoma. In this study, if there is no rate of field cancerization then at equilibrium is not going on invasion carcinoma.

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.