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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinicopathological analysis of giant ovarian tumors.

Objective: This study aims to analyze giant ovarian tumors' clinical and pathological characteristics. Material and Methods: This was an analytical observational study. Medical records of all patients with giant ovarian tumors who underwent surgery between January 2020 and June 2022 at Dr. Soetomo Academic Hospital, Surabaya, Indonesia, were analyzed. Results: We analyzed 63 patients with ovarian tumors measuring > 20 cm who underwent surgery at Dr. Soetomo Academic Hospital, Surabaya, Indonesia. The mean tumor size was 25.9 cm (largest size was 41 cm). There was no significant difference in tumor size between benign and malignant giant ovarian tumors (p = 0.261). Based on histopathological results, 66.67 % of giant ovarian tumors were malignant, 26.98 % were benign, and 6.35 % were borderline. Among the malignant tumors, the epithelial type accounted for 69 % of cases. Most giant ovarian tumors originated in the left adnexa (68.25 %). There was no significant difference in patient age (p = 0.511), tumor size (p = 0.168), malignancy (p = 0.303), and histopathological type (p = 0.232) regardless of adnexal side. CA125 levels did not differ significantly between malignant and benign giant ovarian tumors (p = 0.604). There was no correlation between malignant ovarian tumor size and CA125 levels, while there was a significant difference between CA125 levels and the adnexal side (p = 0.010). Conclusions: Most giant ovarian tumors were malignant, diagnosed at an early stage, and predominantly epithelial type. CA125 levels did not correlate with the size of malignant ovarian tumors. Most giant ovarian tumors originate in the left adnexa.

Correlation between estrogen receptor and programmed death ligand-1 in type I endometrial cancer.

Objective: To determine the effect of estrogen receptor (ER) on programmed death-ligand 1 (PD-L1) expression in type I endometrial cancer (EC). Material and Methods: This retrospective study included 85 patients with type I EC who underwent surgery at Dr. Soetomo Hospital between 2018 and 2022. A random sampling technique was employed. Immunohistochemistry (IHC) with ER and PD-L1 antibodies was performed on all samples. In this study, ER expression served as the independent variable, while PD-L1 expression was considered the dependent variable. Data analysis was performed using Spearman's rank correlation coefficient test. Results: Out of the 85 patients with type I EC, 58 (68.2%) exhibited positive and 27 (31.8%) exhibited negative ER expression. Meanwhile positive PD-L1 expression was seen in 67 (78.8%) and 18 (21.2%) exhibited negative PD-L1 expression. The study revealed a strong negative correlation between ER and PD-L1 expression in EC (rho value = -0.886, p-value = 0.0001). Conclusion: ER downregulates PD-L1 in type I EC. The findings of this study can be used as reference data and as the basis for further research, especially investigations of the prognostic and immunotherapeutic value of ER and PD-L1 expression in type I EC.

The challenging journey of cervical cancer diagnosis and treatment at the second largest hospital in Indonesia.

Objectives: Cervical cancer is a major health concern in developing countries. Access to preventive measures is limited in low- and middle-income countries, and cervical cancer is often identified at an advanced stage of the disease. In this study, we aimed to investigate when patients were first diagnosed and received treatment at a large hospital in Indonesia. Methods: Data were collected using a questionnaire from outpatient visits and descriptively analyzed. Totally, 215 cervical cancer patients being treated at the Dr. Soetomo Academic Hospital's gynecological oncology outpatient clinic in Indonesia between August and October 2022 were included. Results: Most patients were 51-60 years old (36.3 %), housewives (87 %), and had an elementary school education level (50 %). Most (88.4 %) admitted they were unaware about cervical cancer prevention, and 85.6 % never underwent screening. Most cervical biopsies were performed at primary hospitals (42.3 %). Fear of cancer treatment was the most frequent reason for patients arriving late at tertiary hospitals (50 %). Treatment delays occurred because patients had to visit two healthcare facilities before visiting a tertiary hospital (47.4 %). Most patients were diagnosed with stage III cancer (38.1 %), and chemotherapy was administered as the first-line therapy (96.3 %). Most patients (51.2 %) received their first therapy >12 months after initial symptom onset. Conclusions: Most cervical cancer patients were diagnosed at a late stage owing to a lack of information regarding early symptoms and irregular screenings. Treatment was delayed owing to social barriers. Therefore, the government should have more strict policies to implement cervical cancer detection and prevention.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

Experimental Analysis of Vaginal Laxity in Rats Treated With a Combination of Er:YAG Fractional Lasers and AMSC-MP.

Introduction: Vaginal laxity, a symptom of pelvic floor dysfunction observed in women, has many negative biological and psychological impacts. Laser treatments and stem cell-based therapies are emerging therapeutic methods for treating this condition. This study aimed to determine changes in vaginal laxity in model rats using a combination therapy of erbium-doped yttrium aluminium garnet (Er:YAG) fractional lasers and topical treatment with amniotic membrane stem cell metabolite products (AMSC-MP). Methods: The experimental animal population comprised 36 female white rats (Rattus norvegicus; 2-day-post-vaginal-delivery rats) allocated into the following four groups (n=9): K1, untreated two-day-post-vaginal-delivery rats; K2, two-day-post-vaginal-delivery rats treated with topical gel without AMSC-MP; P1, two-day-post-vaginal-delivery rats treated with Er:YAG fractional lasers and topical gel without AMSC-MP; P2, two-day-post-vaginal-delivery rats treated with Er: YAG fractional lasers and topical gel containing AMSC-MP. Immunohistochemical (IHC) examination was carried out for the expression and activity of heat shock protein 70 (HSP-70), collagen-1, tissue inhibitors of metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 1 (MMP-1), as well as vaginal mucosal thickness. Results: There was a significant difference (P<0.05) in the expression of HSP-70 among all groups except K2 and P1 (P>0.05); there was no significant difference in type I collagen and TIMP-1 expression between the groups (P>0.05); there was a significant difference (P<0.05) in MMP-1 activity, with the activity in the K2 group (5.79±0.83) being higher than that in the P1 group (4.44±1.82) and that in the K1 group (5.74±1.03) being higher than that in the P2 group (4.24±1.55). Also, there was a significant difference in the thickness of the vaginal mucosa in all groups except K2 and P1 (P>0.05). Conclusion: Er:YAG fractional laser and AMSC-MP combination therapy improved vaginal laxity in model rats by increasing Hsp70 expression and vaginal mucosal thickness and decreasing MMP-1 activity.

Advanced Stage Clear Cell Ovarian Carcinoma Mimicking Uterine Sarcoma Without Gross Residual Tumor During Primary Surgery: A Case Report.

Background: Clear cell ovarian carcinoma is rare and accounts for 1%-12% of ovarian epithelial carcinomas, depending on ethnicity. The prevalence of clear cell ovarian carcinoma in Asian, White, and Black women is 11.1%%, 4.8%, and 3.1%, respectively. Magnetic resonance imaging (MRI) shows that clear cell ovarian carcinomas are typically unilocular cyst-solid (34.9%) or multilocular-solid (41.4%); only 23.7% are solid with papillary projections. MRI can detect clear cell ovarian carcinoma with a sensitivity and specificity of 90% and 87%, respectively. Notably, sometimes ovarian masses have a solid feature and should be differentiated from uterine masses. Clear cell ovarian carcinoma has a better prognosis compared to serous carcinoma when diagnosed at an early stage, but it has a poorer prognosis at an advanced stage. The absence of a residual tumor is a favorable prognostic factor in patients with advanced-stage clear cell ovarian carcinoma. Herein, we present a case in which clear cell ovarian carcinoma was misdiagnosed as uterine sarcoma because imaging showed a mass with a solid uterine-like and necrotic area. In the present case, cytoreductive surgery was performed to remove the entire tumor and its infiltration to the sigmoid colon and left ureter. Hence, the patient had a better prognosis. Case report: A 57-year-old Indonesian woman presented to our hospital (Dr. Soetomo General Hospital) with post-menopausal bleeding, a large solid pelvic mass, and abdominal discomfort. The patient was diagnosed with uterine sarcoma due to the solid feature observed during ultrasonography and MRI. During the surgery, the mass was observed to originate from the left ovary, and primary debulking surgery with a multidisciplinary team was performed with zero residual tumor tissue. The tumor was histopathologically confirmed as clear cell carcinoma. Conclusion: MRI of clear cell ovarian carcinoma can be misdiagnosed as uterine sarcoma due to its solid feature. Additionally, the enlarged mass distorts the anatomical landmarks. Surgery with no residual tumor improves the prognosis for advanced-stage clear cell ovarian carcinoma.

A questionnaire study on disparity of cervical cancer prevention programs in Asia-Oceania.

BACKGROUND: Despite the introduction of cervical cancer screening and human papillomavirus (HPV) vaccines, the utilization pattern was not standardized. The aim of this study was to elicit the current prevention care in Asia-Oceania. METHODS: An online questionnaire was circulated to different countries/cities in Asia-Oceania. The primary objective was to evaluate the coverage of HPV vaccination and cervical screening programs. The secondary objectives were to study the structures of these programs. Five case scenarios were set to understand how the respondents manage the abnormal screening results. RESULTS: Fourteen respondents from 10 countries/cities had participated. Cervical cancer ranked the first in Myanmar and Nepal. About 10%-15% did not have national vaccination or screening program. The estimated coverage rate for vaccination and screening varied from less than 1% to 70%, which the coverage ran in parallel with the incidence and mortality rates of cervical cancer. All regions approved HPV vaccines, although only four provided free or subsidized programs for nonavalent vaccine. Cervical cytology remained the most common screening tool, and 20%-30% relied heavily on visual inspection using acetic acid. The screening age groups varied in different regions. From the case scenarios, it was noted that some respondents tended to offer more frequent screening tests or colposcopy than recommended by international guidelines. CONCLUSION: This study revealed discrepancy in the practice of cervical cancer prevention in Asia-Oceania especially access to HPV vaccines. There is an urgent need for a global collaboration to eliminate cervical cancer by public education, reforming services, and medical training.

The relationship between maternal death due to COVID-19 and the human development index in East Java, Indonesia.

Background: Maternal mortality rates and human development indexes can reflect a country's quality of health services. During the COVID-19 pandemic, these two achievement indicators are predicted to experience significant changes, and both have an interrelated relationship. Objectives: To find the relationship between maternal death due to COVID-19 and the Human Development Index (HDI) in East Java, Indonesia. Design and methods: A cross-sectional analytic study was carried out by processing secondary data from the provincial department of health regarding maternal mortality due to COVID-19 in East Java in 2020 and the HDI data from the Indonesian Central Statistics Agency. After that, the data were analyzed statistically using SPSS Statistics. Results: The number of maternal deaths due to East Java's COVID-19 during 2020 was 793 out of 1280. Furthermore, the HDI reached 2744.6, the first dimension contains life expectancy reaching 2725.3, and the number of health workers 100,021. In the second dimension, the literacy rate reaches 3482.9, and the average length of schooling is 134,341. Moreover, the last dimension contains a total population density of 40,878,789, and a poverty rate of 4572.7. Statistical analysis results show a positive relationship between maternal mortality due to COVID-19 and HDI, with a p-value of 0.008. Conclusion: There is a significant relationship between maternal mortality due to COVID-19 and HDI. However, the link between maternal mortality and COVID-19 related to the detailed dimensions contained in the HDI is not statistically related.

Comparative analysis of lumbar quadratus lumborum block and epidural block for analgesia in uterine surgery at Dr. Soetomo Hospital, Surabaya.

Over 80% of surgical patients experience postoperative pain, which, if inadequately managed, can lead to complications, prolonged rehabilitation, chronic pain, and decreased quality of life. Epidural block and quadratus lumborum block are techniques commonly used for postoperative pain management. This comparative analytic study aimed to analyze the differences in the analgesic effects of quadratus lumborum block and epidural block in uterine surgery at Dr. Soetomo General Hospital. The outcomes assessed were the numerical rating score (NRS) as a pain score and the administration of opioids as an adjuvant analgesic. Statistical analysis employed the Mann-Whitney test and Chi-square test. The study included 32 patients who underwent uterine surgery at Dr. Soetomo General Hospital and met the inclusion and exclusion criteria. Among the patients, 90.6% experienced mild pain, and 9.4% experienced moderate pain. Epidural blocks were performed in 50% of the patients, while quadratus lumborum blocks were performed in the other 50%. Additionally, 9.4% of the patients received opioids as adjuvant analgesics. The Mann-Whitney test revealed no significant difference in NRS between the epidural block and quadratus lumborum block groups (p-value>0.05). However, the Chi-square test indicated a significant difference in NRS between patients who received additional opioids as adjuvant analgesics and those who did not (p-value<0.00). There was no significant difference in NRS between patients who underwent epidural block and quadratus lumborum block as analgesic techniques.

Occult leiomyosarcoma simulating malignant ovarian tumor: A case report.

INTRODUCTION AND IMPORTANCE: Leiomyosarcoma (LMS) is a malignant tumor of the uterine smooth muscle. It is highly aggressive and accounts for 1 % of all uterine malignancies. Symptoms often include a rapidly growing mass, with an average course of illness ranging from six to eight months. Leiomyosarcomas are rare in younger individuals. CASE PRESENTATION: A 31-year-old nulliparous woman was diagnosed with a suspected malignant ovarian tumor. A unilateral salpingo-oophorectomy and surgical staging were planned to preserve the patient's fertility. However, the large solid mass was found to be arising from the uterus during surgery. In light of the preference for fertility preservation, a myomectomy was performed, with subsequent pathology results showing a malignant leiomyosarcoma. Following counseling and discussion with the patient and her spouse, follow-up surgery was performed to ensure a free surgical margin. CLINICAL DISCUSSION: Leiomyosarcomas at a young age is very rare, and early diagnosis is quite a challenge, especially when the tumor characteristics are not atypical. Thus, surgical evaluation and staging are paramount. CONCLUSION: Surgical diagnosis of any mass with a history of rapid enlargement and characteristics of malignancy is very important, especially when anatomical landmarks are distorted due to the enlarged mass.

Treating Vaginal Relaxation Syndrome Using Erbium: Yttrium Aluminum Garnet Fractional Laser: A Retrospective Study.

Objectives: Vaginal relaxation syndrome (VRS) comprises vaginal laxity and stress urinary incontinence (SUI). Laser vaginal tightening (LVT) therapy using a fractional erbium:yttrium aluminum garnet (Er:YAG) 2.940 nm laser may represent a nonsurgical option for both complaints. This study evaluates the effectiveness and side effects of fractional Er:YAG laser therapy in VRS patients. The improvement in VRS was evaluated. Materials and Methods: This is a retrospective study analyzing the medical records of patients treated with fractional Er:YAG laser therapy in our private clinic in Surabaya, Indonesia. Objective questions were asked to rate patients' satisfaction with the results of the therapy, namely dissatisfaction, and mild, moderate, or strong satisfaction. Statistical analysis used, data were input into tables in Microsoft Excel. Results: Twenty-four VRS patients (54% with vaginal laxity, 33% with SUI, and 13% with vaginal laxity and SUI) were studied. Most of the patients were 36-45-year-old and had 2 children, and 79% of the patients had had a vaginal delivery. After 3 LVTs, mild satisfaction was observed in 15% of patients, moderate satisfaction was noted in 54% of patients, and high satisfaction was noted in 31% of patients. Among 11 patients with SUI, 36% recovered after the first LVT, and 100% recovered after the second LVT therapy. One patient experienced mild fluor albus as a side effect. Conclusion: LVT therapy with a fractional Er:YAG laser was determined to be effective and safe as a treatment for VRS.

Cesarean scar pregnancy with devastating profuse vaginal bleeding.

A cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy that does not have any obvious signs or symptoms. However, the gestational sac in CSP is often embedded in the myometrial scar from the previous cesarean section. We report two cases of CSP in women with a history of cesarean sections who experienced profuse vaginal bleeding. The patients underwent hysterectomy at their own request due to devastating bleeding. CSP is one of the complications of cesarean sections. The patient may present with devastating bleeding, and immediate management is necessary. In a woman who is early into her pregnancy and has a history of cesarean section with profuse vaginal bleeding, CSP is one of the possible diagnoses.

Laparotomy for Abdominal Adhesion and Removal of Intrauterine Device from Anatomically Distorted Uterus due to Adhesion in a 43-Year-Old Woman with 3 Previous Cesarean Sections.

BACKGROUND Adhesion is a complication of cesarean section. Adhesion of the uterus to the bladder or abdominal wall due to cesarean section can cause discomfort and anatomic distortion. Furthermore, removing intrauterine devices (IUDs) becomes challenging with anatomic distortion of the uterus. This report describes the case of a woman with a history of 3 previous cesarean sections who required laparotomy for abdominal adhesion and removal of an IUD from an anatomically distorted uterus due to adhesion. CASE REPORT The patient was a 43-year-old woman who presented with pelvic pain. She had an IUD inserted 2 months after her third cesarean delivery 7 years earlier and started to experience chronic pelvic pain with regular and painful menstruation over the last 4 years and worsening since the last 1 year. On clinical evaluation, the thread of the IUD was missing, and ultrasonography confirmed the presence of the IUD inside the uterus. Because the cervix could not be visualized on speculum examination, vaginal removal of the IUD was considered impossible. Since the IUD could not be removed via the vaginal route and hysteroscopy and laparoscopy could not be performed, the patient underwent laparotomy. It was found that the uterus was severely adhered to the abdominal wall, and the IUD was located inside the uterus. Adhesiolysis and IUD removal were performed. The patient was relieved from the chronic pelvic pain. CONCLUSIONS This report demonstrates the risk of adhesion after multiple cesarean deliveries and the required surgical intervention performed to remove an IUD and adhesiolysis.