Role of CD44 and CD24 Expression on 2-years Disease Free Survival in Patients with Advanced Epithelial Ovarian Carcinoma.

OBJECTIVE: Ovarian cancer is one of the most common cancers with a high mortality rate worldwide. Despite optimal surgical therapy and chemotherapy, recurrence is still common. Cancer stem cells expressing CD44 and CD24 are thought to be contributing factors in recurrence. METHODS: A cohort retrospective study with survival analysis was carried out on advanced ovarian cancer patients who underwent optimal debulking surgery followed by 6 cycles of chemotherapy at Cipto Mangunkusumo General Hospital and Fatmawati General Hospital from January 2019 to March 2023. Immunohistochemical examination was performed on tumor tissue with CD44 and CD24 expression were assessed using the H-Score method then determined the cut off-point expression level using the ROC curve. Furthermore, the relationship between these expression levels with the disease-free survival was assessed using the survival curve. RESULTS: There were 48 subjects who were included in the study. There were high expression levels of CD44 in 47.9% and CD24 in 50% of cases. High CD44 expression had mean and median survival of 13.2 ± 1.8 and 11 months (HR 5.05, 95% CI 1.84- 13.85). High CD24 expression had mean and median survival of 13.5 ± 2.4 and 7 months (HR 7.73, 95% CI 2.58 - 23.15). The combination of the two high expressions had mean and median survival of 10.44 ± 1.88 and 7 months. CONCLUSION: High expression of CD44 and CD24 will shorten the disease-free survival of patients with advanced ovarian cancer.

High ALDH-1 Expression Predicts Non-Complete Response of Radiotherapy in Stage III Squamous Cell Cervical Carcinoma Patients.

BACKGROUND: ALDH1 is a cervical cancer stem cell marker that has radioresistance profile. Recurrence and metastasis following radiotherapy are still being problems of most patients. This study aimed to determine the correlation between ALDH1 and radiotherapy response in stage III squamous cell cervical carcinoma (SCCC) of the cervix. METHODS: A total 58 of 360 patients of stage III SCCC who received external beem radiation and brachytherapy (2016-2021) at Cipto Mangunkusumo Hospital met the eligibility criteria of this study. Pre- and post-irradiation MRI examinations and ALDH expression with immunohistochemistry (Santa Cruz®) were performed on formalin-fixed paraffin-embedded of pre-treatment cervical tissue biopsy taken from RSCM pathological anatomy laboratory. Patients were divided into two groups, complete responders vs non-complete responders. ALDH-1 scores were compared between two groups to assess ALDH-1 expression. The statistical analyses were carried out by SPSS 24. RESULTS: The optimal ALDH-1 score cut-off point on the radiation response was 166.05 pg/mL which was obtained from the analysis of the ROC curve. The AUC value was 0.682 with sensitivity and specificity, 63,6% and 64%, respectively. ALDH score ≥166.05 increased the risk by 3.127 times for not achieving complete response (adj OR 3.127, 95% CI 1.034 - 9.456, p = 0.043). Pre-radiation tumor size (p = 0.593), degree of differentiation (p = 0.161), renal abnormalities (p = 0.114), and keratinization (p = 0.477) were not associated with radiation response. CONCLUSIONS: High ALDH expression was associated with non-complete radiation response in stage III squamous cell cervical carcinoma. 
.

Is there any difference in insulin resistance status between cases of benign and malignant ovarian neoplasms? A study on surrogate markers of insulin resistance in Indonesian non-diabetic women.

The association between insulin resistance (IR) and ovarian neoplasm is little known. The present study attempted to investigate the difference in clinicopathological characteristics, metabolic parameters, and IR prevalence between benign and malignant ovarian neoplasms. The cross-sectional study involved 52 non-diabetic women with benign (n=27) and malignant (n=25) diagnoses in a tertiary hospital in Indonesia. Fasting insulin level (FIL), homeostatic model assessment of IR and ß-cell dysfunction (HOMA-IR and HOMA-ß), fasting IR index (FIRI), and quantitative insulin sensitivity check index (QUICKI) were used as surrogate markers to evaluate IR. Parametric and nonparametric statistical tests were employed to analyze the different parameters between the two groups. Pearson or Spearman's rank test assessed the correlation between markers and clinical variables. Results revealed that patients with benign neoplasms were younger than those with malignant neoplasms (38.63 vs. 47.40 years; P=0.003) and had a higher median body mass index (BMI) than their counterparts (22.98 vs. 18.61 kg/m2; P=0.014). Different characteristics between benign and malignant neoplasm cases were found in menopausal status, ovary side affected, systolic blood pressure, and BMI classes. Endometrial cysts and mucinous carcinoma were the most often diagnosed benign and malignant neoplasms. Malignant neoplasms had a lower median HOMA-ß score than benign neoplasms (49.33 vs. 75.79; P=0.011), indicating more severe ß-cell dysfunction. No significant difference was observed in the prevalence of IR between benign and malignant ovarian neoplasms for the following values of each marker: FIL (25.9% vs. 12.0%), HOMA-IR (37.0% vs. 28.0%), FIRI (51.9% vs. 48.0%) and QUICKI (81.5% vs. 92.0%). The indicators of FIL, HOMA-IR, HOMA-ß, FIRI, and QUICKI correlated with each other and confirmed the reliability of these surrogate markers for measuring IR status in ovarian neoplasms. In brief, benign ovarian neoplasms tended to have more IR when compared with malignant ovarian neoplasms. However, this difference was not statistically significant.

Knowledge, attitudes, and practices among Indonesian urban communities regarding HPV infection, cervical cancer, and HPV vaccination.

BACKGROUND: Few studies explored Indonesian understanding of cervical cancer (CC) and the human papillomavirus (HPV) vaccination. We aimed to investigate the association between knowledge, attitudes, and practices (KAP) and socio-demographical influences related to HPV, CC, and vaccination among Indonesian urban citizens. METHODS: We conducted an online survey during March 2020-August 2021 using the Snowball sampling technique. The socio-demographic characteristic and KAP responses were collected via Google Forms from 400 respondents in Jakarta. The knowledge and attitudes were divided into HPV and CC (aspect 1) and HPV vaccination (aspect 2). Correlation between KAP scores was performed using Spearman's test, and multiple logistic regression analyses were conducted to determine KAP predictors. RESULTS: Indonesian urban citizens in Jakarta were found to have poor knowledge in individual aspects of the inquiry but moderate knowledge overall, good attitude in inquiry both in each aspect and overall, and unsatisfying practices. Overall, in the general population, men, and women respectively: 50.8%, 32.4%, and 53.6% had good knowledge; 82.0%, 75.2%, and 84.4% expressed positive attitude; and 30.3%, 15.2%, and 35.6% applied favorable practice regarding questions inquired. Knowledge was weakly correlated towards attitude (ρ = 0.385) but moderately correlated with practice (ρ = 0.485); attitude was moderately correlated with practice (ρ = 0.577), all results: p<0.001. Significant odds ratio (OR) for predictors to good knowledge were female sex (OR = 2.99), higher education (OR = 2.91), and higher mother's education (OR = 2.15). Factors related to positive attitudes were higher mother's education (OR = 4.13), younger age (OR = 1.86), and better results in the knowledge inquiries (OR = 2.96). Factors that suggested better practices were female sex (OR = 2.33), being employed (OR = 1.68), excellent knowledge scores (OR = 4.56), and positive attitudes expressions (OR = 8.05). Having done one vaccination dose and intention to receive vaccines were significantly influenced by good KAP. CONCLUSIONS: KAP had inter-association to successful CC and HPV prevention programs, and socio-demographical characteristics are critical to influencing better KAP.

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. RESULTS: From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 - 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 - 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 - 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 - 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 - 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 - 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 - 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 - 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 - 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 - 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. CONCLUSION: Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.

Early Gestational Age Placenta Accreta Case Report: Can We Avoid Missed Diagnosis?

BACKGROUND Placenta accreta is an abnormal invasive placenta that can be life-threatening because of the risk of hemorrhage. Its incidence has increased due to high cesarean delivery rates. Early gestational age placenta accreta is difficult to diagnose and misdiagnosis can lead to inappropriate treatment. CASE REPORT Patient 1, a 34-year-old woman (para 2 abortus 1) with 2 previous cesarean deliveries, was referred to our department for vaginal bleeding and abdominal pain. She received 2 curettages for blighted ovum; then, ultrasound examination found uterus perforation and fluid in the Douglas cavity. Exploratory laparotomy confirmed uterine perforation, and a hysterectomy was performed. Histopathological examination revealed placenta accreta. Patient 2, a 35-year-old woman (para 3) with 3 previous cesarean deliveries, was treated at a previous hospital for vaginal bleeding and stomach enlargement. She received serial chemotherapy for gestational trophoblastic neoplasia. Ultrasound examination showed a nonhomogeneous opacity in the lower uterine corpus with color score 4. Total abdominal hysterectomy was performed, and histopathological examination revealed placenta accreta. Patient 3, a 32-year-old woman (para 2) with 2 previous cesarean deliveries, had irregular vaginal bleeding suspected as gestational trophoblastic neoplasia due to ultrasound examination and positive beta-human chorionic gonadotropin. Ultrasound and MRI examination showed enlargement with nonhomogeneous opacity, color score 4, and bridging vessels. Due to our previous experience, we suspected it was a placenta accreta and performed a hysterectomy. The histopathology result indicated placenta accreta. CONCLUSIONS The key point in diagnosing placenta accreta properly is to evaluate the morphometric changes based on the structure using imaging like ultrasound. Collection and analysis of these data enables precise diagnosis in early gestational age placenta accreta.

Tobacco use and its association with HPV infection in normal uterine cervix: A study from a Sustainable Development Goals perspective.

INTRODUCTION: To achieve the Sustainable Development Goals (SDGs) target 2030, the United Nations (UN) endorsed tobacco use reduction, which is essential in decreasing unnecessary deaths caused by tobacco-induced disease. This study investigates the association between tobacco use and Human Papillomavirus (HPV) infection in clinically normal uterine cervix populations from the SDGs perspective. METHODS: This study is a 7-year cross-sectional study of a clinically normal uterine cervix population, based on negative Visual Inspection of Acetic Acid (VIA). Subjects were recruited consecutively from the medical records of several public and private health providers in Jakarta. The Statistical Product and Service Solutions (SPSS) for Windows version 20.0 were used to analyze the data. RESULTS: A total of 1397 negative VIA subjects were collected, consisting of 4.9% (69/1397) tobacco users, and 95.1% (1328/1397) non-users. HPV-DNA positive were 4.3% (3/69) in the tobacco user group and 3.7% (49/1328) in the non-user group. Statistical analysis showed unadjusted OR was 1.19 (95% CI: 0.36-3.91, p=0.778) and adjusted OR was 1.18 (95% CI: 0.36-3.89, p=0.786). High-risk HPV (hrHPV) infections of tobacco and non-tobacco users' groups were found in 2/3 and 27/49 (55.1%), respectively. CONCLUSIONS: This study showed an insignificant statistical association between tobacco use and HPV infection in normal uterine cervix. However, the proportion of hrHPV infection was higher in tobacco users than non-users. From the SDGs perspective, cervical cancer is closely related to tobacco use and poverty. Further study is needed to support this result and evaluate other co-factor role-related cervical cancer history to achieve SDGs in 2030.

Skin metastases originated from cervical cancer: A rare case report.

INTRODUCTION: Metastases in cervical cancer could be spread through direct local invasion, lymphatic dissemination, or hematogenous dissemination. The most common sites of distant metastases are lungs, bone, and liver. Skin metastases from cervical cancer are categorized as a rare occurrence of metastases. This rarity of the cases has led us to report it. CASE DESCRIPTION: A 66-year-old multiparous woman diagnosed with stage IIA cervical cancer seven years ago, then she came into our outpatient clinic complained about a brownish white color mass on the left side of the neck that keeps getting bigger over time came from a skin lesion. The lesion was first treated with topical steroid but there was no improvement. Biopsy was done and the result showed a carcinoma metastasis that led to adenosquamous carcinoma or cervical adenocarcinoma. The patient went through chemoradiation with biosensitizer paclitaxel 120 mg/m2 for six cycles, which began in August 2019 until October 2019. The treatment progress showed a promising result. We observed the patient during treatment until two months after finishing the treatment. At the last visit, the patient came to our outpatient clinic, the mass size decreased significantly, and the skin showed an excellent regeneration sign. CONCLUSION: The physicians should always consider the patient's history and pay more attention to skin lesions in patients with a history of cervical cancer. The physicians should also perform a thorough physical examination and biopsy to confirm the diagnosis.