Dynamic Changes in Body Composition and Protein Intake in Epithelial Ovarian Cancer Patients Undergoing Chemotherapy: A Preliminary Study.

BACKGROUND: Ovarian cancer patients often face poor nutritional status, with body composition (BC) serving as a significant prognostic indicator. Skeletal muscle mass (SMM) and fat-free mass (FFM) are crucial predictors of both survival and hospitalization duration. Increasing protein intake has been linked to improvements in SMM and FFM. OBJECTIVE: This study aimed to document the alterations in BC parameters among ovarian cancer patients undergoing chemotherapy and correlate these changes with their nutrient intake. METHODS: Twelve female patients with stage III ovarian cancer who received first-line chemotherapy were categorized based on their body mass indices (BMI). BC parameters were assessed using an 8-point bioelectrical impedance analysis with a frequency of 50 Hz-60 Hz and measurement impedance range of 10 Ω-1000 Ω. Nutrient intake (energy, protein, fat, and carbohydrate) was assessed before (T0), during the 3rd (T3), and 6th cycle of chemotherapy (T6) through 24-hour food recall. RESULTS: Significant increases in body weight (BW)were observed in the underweight group (from 40.9 to 46.8 kg, p=0.001), concomitant with enhancements in all BC parameters. While changes were noted in SMM, they were not statistically significant (p=0.105).Among the underweight group, a protein intake above 1.2 g/kg BW led to an uptrend trend in SMM. Conversely, FFM in overweight/obese patients decreased significantly (from 37.6 to 36.4 kg, p=0.005) due to a a reduction in body water. Throughout chemotherapy, fat mass (FM), visceral fat (VAT), and phase angle (PhA) increased in all patient groups, reflecting heightened fat and carbohydrate intake. CONCLUSION: Among stage III ovarian cancer patients, BC undergoes dynamic changes dynamically during the course of chemotherapy, with more pronounced enhancements observed in FFM among underweight patients. Notably, improvements in PhA, SMM or FFM were particularly evident among underweight patients with a protein intake above 1.2 g/kg BW.

Establishment of Epithelial Cell Culture from Ovarian Cancer Tissues: A Method Comparison Study.

OBJECTIVE: This study aimed to determine the most effective method in establishing primary cell culture from epithelial serous ovarian cancer tissues with the highest yield of cells and percentage of epithelial cells. METHODS: Primary and metastasis tissues from three serous ovarian cancer patients were processed using 18 different combinations of methods based on different factors: the source of tissue (primary site or metastasis site), the cell suspension method (explant method, enzymatic methods, or the addition of Percoll), and the alternatives of three different media. We compared the total count of cells, the percentage of epithelial cells, and the estimated number of epithelial cells per observation field. The calculation of cells from primary tissues were compared to metastasis tissues, and the difference was statistically analyzed using Mann Whitney-U test on SPSS software. RESULT: The groups that were processed using dispase and trypsin resulted higher number of cells and higher percentage of epithelial cells when compared to the explant method. Among all media, we found that DMEM:F12 and McCoy's 5A media as equally useful in isolating and culturing epithelial cells. Statistically, the metastasis tissue derived more epithelial cells when compared to the primary tissue (102.32±82.65 vs 22.6±23.81, p=0.001). CONCLUSION: The use of metastasis tissue processed with trypsin or dispase and cultured in DMEM:F12 or McCoy's 5A media was found to be the most efficient way to produce the highest amount of cells with high percentage of epithelial cells.

CD44+/CD24- Expression as predictors of ovarian cancer chemoresistance: immunohistochemistry and flow cytometry study.

BACKGROUND: The conventional standard treatment for ovarian cancer is not very effective, and the disease is fatal for women. Cancer Stem Cells (CSCs) that express CD44+/CD24- can contribute to chemoresistance and a poor prognosis. We seek to investigate the expression of CSCs (CD44+/CD24-) in ovarian cancer and their predictive significance. METHODS: The ambispective cohort was performed on 64 patients (32 patients in each group) at four hospitals (Cipto Mangunkusumo, Tarakan, Fatmawati, and Dharmais Hospital). Debulking surgery was performed on the patients, followed by histopathological analysis. The patients had six rounds of chemotherapy and were under monitoring for six months. The therapeutic responses were evaluated using the RECIST criteria (Response Criteria in Solid Tumors) and categorized as chemoresistant or chemosensitive. Using immunohistochemistry, we directly assess the CSCs from ovarian cancer tissue and using flow cytometry to assess the CSCs from the blood. RESULTS: High CSCs expression and ovarian cancer chemoresistance were significantly related in both trials (p 0.05). A better outcome was obtained using CD44+/CD24- immunohistochemistry. CONCLUSIONS: We conclude that there is a substantial association between high CSCs expression and chemoresistance in ovarian cancer and that CSCs immunohistochemistry has a higher predictive value.

Possible different genotypes for human papillomavirus vaccination in lower middle-income countries towards cervical cancer elimination in 2030: a cross-sectional study.

Purpose: Human papillomavirus (HPV) genotype and age distribution of HPV infection were crucial for the national vaccination and screening program planning. However, there was a limited study providing these data in the normal cervix population. This study aimed to explore the HPV genotypes profile of women with clinically normal cervix based on Visual Inspection of Acetic Acid (VIA) test. Materials and Methods: A 7-year cross-sectional study was conducted from 2012 to 2018 in private and public health care centers in Jakarta. Subjects were recruited consecutively. Data were collected by anamnesis, VIA, and HPV DNA test using the polymerase chain reaction (PCR; SPF10-DEIA-LiPA25) method. HPV genotyping procedures include DNA extraction, PCR (SPF10-DEIA-LiPA25) using the HPV XpressMatrix kit (PT KalGen DNA, East Jakarta, Indonesia), and hybridization. The IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA) were used to analyze the data. Results: A total of 1,397 subjects were collected. Positive HPV-DNA tests were found in 52 subjects (3.7%); 67% were single and 33% were multiple HPV infections. HPV 52 was the most frequently detected HPV genotype, followed by HPV 39, 16, 18 74, 44, 31, 54, and 66, respectively. The highest HPV infections in this population were in the 31-40 and 41-50 years old group. Conclusion: This study suggested beneficial screening for women aged 31-50 years old. Instead of "original" nonavalent (HPV 16, 18, 6, 11, 31, 33, 45, 52, 58), the different "nonavalent" formula for HPV vaccines protecting against HPV 16, 18, 6, 11, 31, 39, 44, 52, 74 might be useful for Indonesian population. However, further multicenter studies with a huge sample size are still needed.

The Utility of Pre-Treatment Inflammation Markers as Associative Factors to the Adverse Outcomes of Vulvar Cancer: A Study on Staging, Nodal Involvement, and Metastasis Models.

BACKGROUND: Given the role of inflammation in carcinogenesis, this study investigated the utility of pre-treatment inflammatory markers as associative indicators for advanced-stage disease, lymph node metastasis (LNM), and distant metastasis (DM) in vulvar cancer (VC). METHODS: A cross-sectional study was conducted on 86 women with VC in a single centre in Jakarta, Indonesia. The laboratory data was based on C-reactive protein (CRP), procalcitonin, the erythrocyte sedimentation rate (ESR) and fourteen derived, recorded and calculated ratios: leukocyte-to-platelet (LPR), neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR), neutrophil-to-monocyte (NMR), platelet-to-monocyte (PLR), lymphocyte-to-monocyte (LMR), basophil-to-monocyte (BLR), systemic immune-inflammation index (SII), body mass index, albumin, and NLR (BAN) score, haemoglobin-to-platelet (HPR), prognostic nutritional index (PNI), modified Glasgow Prognostic Score (mGPS), CRP-to-albumin, and CRP-to-procalcitonin. The optimal cut-off for each marker was determined using receiver operating characteristic (ROC) curve analysis, and their diagnostic indicator performances were assessed. The utility of these ratios as associative factors for three endpoints was further evaluated in multivariate regression models. RESULTS: Investigated inflammatory markers exhibited specific performances for individual adverse outcomes, proving a fair to excellent ability in case finding and screening. After adjustment, the BAN score ≤ 334.89 (OR 9.20, p = 0.001) and ESR ≥ 104 (OR 4.18, p = 0.048) become two advanced-stage associative factors with AUC: 0.769. LNM was solely determined by higher NLR ≥ 2.83 (OR 4.15, p = 0.014) with AUC: 0.615. Meanwhile, BLR ≥ 0.035 (OR 5.67, p = 0.001) and ESR ≥ 84 (OR 6.01, p = 0.003) were contributing factors for DM, with AUC: 0.765. CONCLUSIONS: Inflammatory markers are crucial for identifying the deleterious outcomes of VC. Accordingly, yielded models require external validation.

Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer.

OBJECTIVES: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. METHODS: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. RESULTS: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). CONCLUSIONS: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

Post Marketing Surveillance Study of 2nd Dose Quadrivalent Human Papilloma Virus Vaccine in Elementary School Children in Jakarta, Indonesia: Safety Result and Implementation of School-Based HPV Immunization Program

Objective: Quadrivalent human papillomavirus (QHPV) vaccine has been advised for routine vaccination of pre-adolescent girls globally, and a two-dose QHPV vaccination schedule has been introduced in Indonesia to vaccinate 5th and 6th grade elementary school female students. This post-marketing surveillance study evaluated the possible adverse events following immunization with the two-dose QHPV vaccine in Indonesia. Methods: Girls studying in grade 6 of five designated elementary schools in Jakarta, receiving their 2nd dose of QHPV vaccine and provided informed consent (represented by their parents), were included in the study. Students who had received other immunizations either simultaneously or <1 month ago were excluded. Local and systemic reactions noted at 30 min, and 72 h to 28th day, after the immunization were recorded using a Children Symptom Dairy Card/Kartu Harian Anak Sekolah (KHAS/ Student Daily Card). Results: A total of 500 students from 20 schools were included. No serious adverse events were reported during the study period. Fever (systemic reaction) of mild intensity was noted in 1.6 % (n=8) of participants, which subsided after day 6. Local reactions such as pain, redness and swelling were noted in 59.6% (n=295), 23.6% (n=118), and 17.2% (n=86) of participants, respectively. These resolved without any intervention in majority of the cases after day 5. Conclusion: These results along with the safety data from the pre-licensure clinical trials confirm the favorable safety profile of QHPV vaccine in pre-adolescent girls. The school-based two-dose QHPV immunization program in Indonesia is a safe and effective strategy for optimizing HPV vaccine coverage among pre-adolescent girls.

Spirituality-Focused Palliative Care to Improve Indonesian Breast Cancer Patient Comfort.

BACKGROUND: Palliative care is an approach that focuses on improving a patient's quality of life. This research aimed to develop a path model of the relationships between the variables of nursing care (information, emotional support, technical support, and palliative care), patient coping, family support, patient spirituality, and patient comfort expressed through physical and emotional mediators. METHOD: This cross-sectional study involved 308 breast cancer patients from 3 referral hospitals in Jakarta, Indonesia. A structural equation model with Kolcaba's theory was used to develop a theoretical model estimating the path or relationships between the key variables. RESULTS: The results showed that palliative care significantly improved breast cancer patient comfort by reducing anxiety and depression. Furthermore, the study demonstrated a significant positive relationship between spirituality and emotional well-being. CONCLUSION: Spirituality-focused palliative care is fundamentally importance for breast cancer patients. Nurses play an essential role in providing spirituality-focused palliative care to promote comfort in breast cancer patients in Indonesia.

The Cost-Effectiveness of Quadrivalent Human Papillomavirus Vaccination in Indonesia

Objective: National cervical cancer prevention program has been initiated in Indonesia since April 2015 and the ministry of health has started efforts to integrate the HPV Vaccine in the national immunization program since Q4 2015. Thus, it becomes important to analyze the cost-effectiveness of HPV vaccine. The objective of this model is to examine the potential long-term epidemiologic and economic impact of quadrivalent HPV(qHPV;6/11/16/18) vaccination program in Indonesia. Methods: A previously validated transmission dynamic model was used to estimate the long-term epidemiologic and economic consequences of quadrivalent HPV vaccination by comparing cost-effectiveness of 2 dose qHPV vaccination strategy for girls 11-12 years old (with or without catch up; catch up dose for 12­26 years) versus Screening Only (Pap Smear) for reducing cost related to HPV type 6,11,16,18 (cervical cancer, CIN 1, CIN 2/3, and genital warts). Costs of an HPV disease episode-of-care (diagnosis and treatment) were calculated for base case analysis using local Indonesian cost. Result: 2-dose qHPV vaccination strategies without catch up reduce the overall incidence of HPV 16/18­related cervical cancer relative to screening by 54.4% over the 100 year following vaccine introduction. Likewise, vaccination strategies reduce the incidence of HPV type 16/18 CIN 2/3, CIN 1 by 69.1% and 71.8% respectively, also reducing HPV type 6/11 CIN 1, genital warts in female, genital warts in male by 82.9%,84.2%,82.1% respectively, at this time point. From total reduction of health care cost, 67.1% attributable for diseases caused by HPV type 16/18 and 32.9% attributable for diseases caused by HPV type 6/11. Without catch up, cost/QALY would be $450/year. However catch-up strategy is more cost effective versus vaccinates 12-year-old girls only; with cost/QALYs would be $390/year. Conclusion: HPV 6/11/16/18 vaccination of females in Indonesia are 1) substantially reduce genital warts, CIN, and cervical cancer; 2) improve quality of life, and 3) with the Indonesia GDP of USD 3,531.80 in 2014 , Cost/QALYs result with or without catch up is considered very cost-effective when implemented; however with catch up, the cost/QALY can be better.