Brahmana Askandar Tjokroprawiro

Comparison of PD-L1, CTR-1, VEGF, and p53 expression in sensitive and resistant epithelial ovarian cancer (EOC) patients to platinum-based chemotherapy

The current standard treatment for ovarian cancer is a combination of cytoreductive surgery and platinum-based chemotherapy; however, many patients develop resistance, leading to a high recurrence rate. The aim of this study was to analyze the expression of PD-L1, CTR-1, VEGF, and p53 in epithelial ovarian cancer (EOC) patients, comparing those sensitive and resistant to platinum-based chemotherapy. A cross-sectional study was conducted among EOC patients who underwent surgery and platinum-based chemotherapy between 2020 and 2023 at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, with evaluations performed six months post-chemotherapy. The expression of PD-L1, CTR-1, VEGF, and p53 were measured using immunohistochemistry (IHC) and compared between chemotherapy-sensitive and resistant patients. A total of 65 patients were included: 31 resistant and 34 sensitive cases. The results showed higher PD-L1 expression in the resistant group compared to the sensitive group (mean combined positive score (CPS) of 0.46±0.29 vs 0.17±0.09, p<0.001). The CTR-1 expression was lower in the resistant group (immunoreactive score 2.90±1.30) compared to the sensitive group (immunoreactive score 6.82±2.68) with p<0.001. VEGF and p53 expression were also higher in the resistant group (6.68±2.59 vs 2.76±1.10 and 64.68±13.54% vs 30.15±13.06%, respectively) compared to the sensitive group, with both having p<0.001. The study suggests that increased expression of PD-L1, VEGF, and p53 and decreased CTR-1 expression are associated with platinum-based chemotherapy resistance among EOC patients. Therefore, these biomarkers might have the potential for predicting treatment responses and understanding resistance mechanisms.

Yolk sac ovarian cancer with mesenteric metastases

We present a rare case of mesenteric metastases of yolk sac ovarian cancer in an early adolescent girl. The patient initially presented with abdominal distension. The patient underwent physical and diagnostic testing, which yielded findings indicative of a malignant ovarian tumour (solid cystic mass and increased levels of tumour markers). Surgery was performed and histological examination revealed a yolk sac tumour that had spread to the mesentery. Chemotherapy was administered. Yolk sac ovarian cancer metastases usually occur in nearby structures; however, mesenteric metastases are rare.

Investigation of the trends and associated factors of ovarian cancer in Indonesia: A systematic analysis of the Global Burden of Disease study 1990–2021

Introduction Ovarian cancer is one of the most lethal gynecological cancers. Despite diagnosis and treatment advances, survival rates have not increased over the past 32 years. This study estimated and reported the global burden of ovarian cancer during the past 32 years to inform preventative and control strategies. Methods We examined ovarian cancer incidence, mortality, and disability-adjusted life years (DALYs) using age-standardized rates from the Global Burden of Disease, Injuries, and Risk Factors Study 2021. high body mass index and occupational asbestos exposure were linked with death and DALYs. Data are presented as averages with 95% uncertainty intervals (UIs). Results Indonesia had 13 250 (8 574–21 565) ovarian cancer cases in 2021, with 5 296 (3 520–8958) deaths and 186 917 (121 866–309 820) DALYs. The burden increased by 233.53% for new cases, 221.95% for mortalities, and 206.65% for DALYs. The age-standardized rate also increased from 1990 to 2021. Ovarian cancer burden increased with age but declined in the 50+ year age group. According to the sociodemographic index, the gross domestic product per capita and number of obstetricians and oncologic gynecologists in provinces showed different trends. Conclusions Indonesian ovarian cancer rates are rising despite gynecologic oncologists in 24 of 34 provinces. These findings will help policymakers and healthcare providers identify ovarian cancer prevention and control gaps.

Cervical Neuroendocrine Carcinoma Presenting as Isolated Large Ovarian Metastasis: A Case Report

BACKGROUND Neuroendocrine carcinoma (NEC) of the cervix is rare and has high mortality and recurrence rates. The clinical symptoms of cervical NEC, such as abnormal vaginal bleeding and discharge, are similar to those of other cervical cancers. Here, we describe a case involving a 42-year-old woman with cervical NEC accompanied by an isolated large ovarian metastasis. CASE REPORT A 42-year-old woman had experienced abdominal discomfort for the past 4 months, along with a larger abdominal circumference. Physical examination revealed a 15-cm, solid, mobile, abdominal mass and a smooth cervix. Abdominal computed tomography revealed a hypoattenuating solid mass with a calcified component and indistinct borders, measuring 16.6×15.5 cm. Tumor marker levels were as follows: cancer antigen 125, 803.9 U/mL; carcinoembryonic antigen, 241.9 ng/mL. Preoperatively, we suspected a malignant ovarian tumor without any suspicion of cervical cancer. Intraoperatively, a 25×20-cm solid mass was found on the left adnexa with peritoneal wall and rectosigmoid adhesions. We performed a total abdominal hysterectomy with bilateral salpingo-oophorectomy, followed by peritoneal biopsy and omentectomy. Histopathological examination showed a 2.5-cm endocervical mass and a normal ectocervical epithelium. Immunohistochemistry revealed a small-cell cervical NEC with metastasis to the left ovary. The final diagnosis was a stage IB2 cervical NEC with ovarian metastasis. For treatment, we administered an etoposide-cisplatin adjuvant chemotherapy regimen. CONCLUSIONS NEC of the cervix can manifest as a large ovarian tumor, lack the usual indications for cervical cancer, and spread to the ovaries without metastasis to other organs.

Estrogen receptor and programmed death ligand-1 expression in type 1 endometrial cancer and its associated clinicopathological characteristics

This study aimed to determine the association of estrogen receptor (ER) and programmed death ligand-1 (PD-L1) expression with the clinicopathological characteristics of type 1 endometrial cancer. A total of 85 patients with type 1 endometrial cancer who underwent surgery at the Dr. Soetomo Hospital, Surabaya, Indonesia were retrospectively studied. Data about the age, menopausal status, body mass index, disease stage, cell differentiation, angiolymphatic invasion, myometrial invasion, and adjuvant therapy of the patients were collected from medical records. Immunohistochemistry with ER and PD-L1 antibodies was performed on all samples. The association between ER and PD-L1 expression and clinicopathological characteristics was statistically analyzed. The positivity rates of ER and PD-L1 in type 1 endometrial cancer were 68.2 % and 78.5 %, respectively. ER positivity was significantly correlated with body mass index (BMI) ≥25, premenopausal status, early stage of disease, <1/2 myometrial invasion, negative nodal metastasis, and lack of adjuvant therapy. It was also associated with age <55 years, low-grade cells, and angiolymphatic invasion, but the correlation was not significant. Meanwhile, PD-L1 positivity was significantly correlated with BMI <25, menopausal status, advanced stage of disease, high-grade cells, angiolymphatic invasion, and adjuvant therapy. It was also associated with age ≥55 years and nodal metastasis, but the correlation was not significant. ER and PDL-1 positivity is associated with the clinicopathological characteristics of type 1 endometrial cancer.

Mismatch Repair Protein Deficiency Does Not Affect Disease Free Survival in Type I Endometrial Carcinoma

This study aimed to analyze the correlation between the 3-year disease-free survival (DFS) and mismatch repair (MMR) protein levels in patients with type 1 endometrial carcinoma. Many studies have reported different results regarding the role of MMR in the prognosis of endometrial carcinoma; therefore, we aimed to identify this association in our hospital. This observational study employed a historical cohort design and included patients with type 1 endometrial carcinoma who underwent surgery at Dr. Soetomo Hospital between January 2017 and December 2019. Medical records and paraffin blocks meeting these criteria were obtained. MMR proteins (MLH1 and MSH2) were assessed using immunohistochemistry. A total of 46 patients with type 1 endometrial carcinoma were analyzed. We observed MMR deficiency (dMMR) in 12 patients (26.1%) and MMR proficiency (pMMR) in 34 patients (73.9%). Of the 12 patients with dMMR, nine cases (75%) were diagnosed as stage I and 7 (58.33%) as low grade. The 3-year DFS in patients with dMMR and pMMR was 83.3% and 67.6%, respectively (Hazard Ratio 2.31, 95% CI 0.5135-10.475, p=0.27). Higher stages had a 5.42 times increased risk of recurrence (95% CI 1.3378-21.9358, p=0.018). Higher histopathological grades were also associated with 8.65 times increased risk of recurrence (95% CI 2.5020-29.8738, p=0.001). Patients with dMMR had a better DFS compared to those with pMMR; however, the difference was not statistically significant. The tumor stage and histopathological grade were independent risk factors for recurrence.

The AOFOG recommendations on human papillomavirus vaccination in the Asia‐Pacific region

AbstractCervical cancer remains a disease burden in Asia. The Asia and Oceania Federation of Obstetrics and Gynecology envisages a need to produce a set of recommendations on the implementation of human papilloma virus vaccination program for both lower‐middle‐income countries (LMICs) and high‐income countries (HICs), with an attempt to harmonize the practices yet allow flexibility to cater for different cultures, religions, needs and background of individual countries/cities. International guidelines and literature were sought, and recommendations were made in seven selected areas, including (i) the target groups for vaccination, (ii) the doses of vaccination including the use of single‐dose vaccination, (iii) the types of vaccines, (iv) suggestions for special populations including those with previous HPV infection, human immunodeficiency virus carriers, and lesbian, gay, bisexual, transgender, questioning/queer group, (v) inter‐changeability and the need of revaccination/booster, (vi) novel technologies and vaccines, and (vii) public education.

A Huge Malignant Ovarian Tumor: A Case Report

BACKGROUND Huge ovarian tumors are rare. In developing countries, many women with huge ovarian tumors only seek consultation when the tumor has become very large. Most cases are benign, and only a few cases were reported to be malignant. This case report presents a case of huge malignant ovarian tumor with a final diagnosis of stage III epithelial ovarian cancer. The tumor was completely removed. The huge malignant ovarian tumor in this case report was completely excisable. CASE REPORT A 43-year-old woman visited the tertiary hospital in Surabaya Indonesia in early September 2020 with a complaint of an enlarged abdomen. The patients had 3 children and normal menstrual periods. Her bowel function was normal. The patient started to notice the abdominal enlargement at 3 months prior to seeking treatment. Ultrasound examination showed a unilocular cystic mass with a diameter of >25 cm, and a solid nodule with normal vascularity was seen. No ascites was noted. Histopathologic examination showed an ovarian mass weighing 9700 g with a size of 30×28×14 cm. The final result showed that the tumor was malignant; specifically, the tumor was a sero-mucinous adenocarcinoma of the left ovary, grade II, which had metastasized to the omentum. CONCLUSIONS Huge malignant ovarian tumors tend to be at an early stage when the diagnosis is made, and they are completely excisable.

Geographic barriers to gynaecological cancer care in Indonesia: a geospatial and infrastructure analysis

Objective This study aimed to identify underserved regions and evaluate the population coverage based on travel time and distance to hospitals with gynaecologic oncologists in Indonesia. Methods The travel time and distance to hospitals with gynaecologic oncologists were evaluated using the Quantum Geographic Information System. Data from 139 gynaecologic oncologists and their affiliated hospitals were obtained from the Indonesian Society of Gynecologic Oncologists (November 2024) and cross-referenced with the Ministry of Health records. The female population density data were sourced from Facebook’s high-resolution settlement layer. Isochrones were generated to estimate travel times and distances using zonal statistics, which facilitated the calculation of population coverage. Results A total of 139 gynaecologic oncologists were identified nationwide, practising in 243 hospitals (7.6% of the 3202 hospitals in Indonesia), with a concentration in Java (60.4%). 11 of the 38 provinces lack sub-specialists. Population coverage varies sharply: the travel time to a hospital with gynaecologic oncologists is ≤2 hours for 79.1% of women in Java, compared with 4.9% in Papua; overall, 34.4% reside more than 100 km away from hospitals with gynaecologic oncologists. Hospitals with gynaecologic oncologists are predominantly urban class B general hospitals, and 83.1% participate in the National Health Insurance Schemes. Exploratory district-level correlations showed positive associations between the number of such hospitals and total female population (r=0.44, p&lt;0.001), female life expectancy (r=0.29, p&lt;0.001), per-capita expenditure (r=0.54, p&lt;0.001), female population density (r=0.68, p&lt;0.001), female Human Development Index (r=0.4, p&lt;0.001) and a negative association with land area size (r=–0.15, p&lt;0.001). Conclusions Gynaecological oncology services in Indonesia remain heavily concentrated in Java, leaving nearly one-fifth of women residing more than 100 km away. The travel time is greater than 2 hours for many. Targeted expansion of the gynaecologic oncologists workforce, diagnostic and treatment infrastructure, and sustainable financing mechanisms are required to close these gaps.

Economic Evaluation of Cervical Cancer Screening by HPV DNA, VIA, and Pap smear Methods in Indonesia

Cervical cancer occurs 80% in developing country including Indonesia and take place in the first rank of incidence rate and third rank in mortality rate in Asian Pacific. Natural history of cervical cancer gives a potential to get accurate screening method. Cervical cancer screening m in Indonesia use VIA and Pap smear method for women in age range 30 to 50 years old. Recently, HPV DNA test has been recommended in international and national policy as primary screening method for cervical cancer. This research aims to  asses cost-effectiveness and economic implications of specific cervical cancer screening modalities. Cost-effectiveness analysis was conducted from societal perspective. Cost data was collected from four hospitals in Indonesia. Direct medical costs were derived from discussions with an expert panel and hospital billing data, aligning with current practice guidelines. Direct and indirect non-medical costs were estimated from patient interviews. Effectiveness data for the screening methods were extracted from a systematic review of existing literature. Markov model design was used for cost-effectiveness analysis. Budget impact analysis used healthcare perspective method from its billing for cervical cancer patients. Cervical cancer screening costs are calculated using direct medical, non-medical, and indirect expenses. Regarding to cost-effective analysis by incremental cost-effective ratio (ICER), pap smear for every 3 and 5 years is more cost-effective than VIA. HPV DNA also has the potential to be cost-effective. The budget impact analysis investigates scenarios, with a focus on negotiation-based cost reductions for HPV DNA testing. Controlling HPV DNA tariffs at USD 8.76 proves cost-effective. In conclusion, pap smear is the most cost-effective modality, while HPV DNA has the potential to be cost-effective by reducing the unit cost. Despite favorable outcomes, challenges in implementation suggest a phased approach for resource equalization before full deployment.