Cancer Stem Cells (CD44+/CD24-), RAD6, DDB2 Immunohistochemistry Expression and IHC-UNEDO Scoring System As Predictor of Ovarian Cancer Chemoresistance.

Backgrounds: Ovarian cancer is a deadly women cancer with many chemoresistance after standard treatment. Ovarian cancer tissues' CD44+/CD24- (CSCs), RAD6 overexpression and DDB2 underexpression are associated with chemoresistance, recurrence, and poor prognosis of the disease because of the existence of cancer stem cells (CSCs). We tried to analyze the expression of those three proteins while building a predictor scoring system to predict the ovarian cancer chemoresistance from the ovarian cancer tissue immunohistochemistry. Materials and Methods: We conducted a cohort study of 64 patients divided into two groups (32 patients in each group) at the Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital which are located in Jakarta city, Indonesia. The patients underwent cytoreductive debulking and histopathological examination continued by six series of chemotherapy followed by six months of observation. We divided the groups into chemoresistant and chemosensitive by using Response Criteria in Solid Tumors (RECIST) criteria. Ovarian cancer tissue immunohistochemistry tests were then performed to count the CSCs, RAD6 and DDB2 expressions. Results: We found relationship between increased CSCs, RAD6 and reduced DDB2 (p < 0.05) expression in ovarian cancer tissue with the chemoresistance. A possible predictor scoring system named IHC-UNEDO scoring was built to aid the ovarian cancer chemoresistance prediction. Conclusions: The conclusion is that CSCs, RAD6 and DDB2 expressions are significantly associated with ovarian cancer chemoresistance, and IHC-UNEDO scoring should be considered as a tool to predict ovarian cancer chemoresistance.

Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer Predicted by CD4+, CD8+, and FOXP3+ Tumor-Infiltrating Lymphocytes.

BACKGROUND: Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses. METHODS: A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis. RESULTS: Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant. CONCLUSION: This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC.

The Role of Stromal Tumour Infiltrating Lymphocytes (sTIL) Intensity and Programmed Death Ligand 1 () Expression in Breast Cancer Response to Neoadjuvant Therapy in Cipto Mangunkusumo Hospital (CMH), Indonesia.

BACKGROUND: Pathological responses to neoadjuvant therapy were still relatively poor, especially in CMH. Studies had been done to search for predictors of response such as sTIL intensity and  expression, which is known to block sTIL action in killing cancer cells. This research assessed sTIL intensity and  expression as predictors of response to neoadjuvant therapy in breast cancer. The preliminary data might be used to better tailored breast cancer patient therapy, considering the availability of anti-PD-1/ PD- L1 immunotherapy nowadays. OBJECTIVE: To assess TIL intensity,  expressions, and their roles as pathological predictors of breast cancer response to neoadjuvant therapy in Cipto Mangunkusumo Hospital (CMH). METHOD: This was an observational analytic retrospective cohort study on breast cancer patients undergoing biopsy/review of biopsy specimens, receiving neoadjuvant therapy and mastectomy in CMH from January 2014 to December 2021. Sixty cases fulfilled the inclusion and exclusion criteria. Total sampling was done.   expression (immunohistochemistry, clone 22C3) and sTIL intensity (histopathology) was examined in the biopsy specimen. Linear regression analysis was done to determine the independent predictors of neoadjuvant therapy response (evaluated in the mastectomy specimen with residual cancer burden/ RCB score). RESULTS: There were 60 female patients, median age 46 years old. 91,7% had invasive carcinoma of no special type. Median sTIL intensity was 10% (1%-70%). 58,3% patients had low sTIL intensity (≤10%). 28,3% patients had positive  expression (CPS ≥1). Only 8,3% patients had pCR, while 90% patients had RCB class II-III. Every 1% increase in sTIL intensity, no lymphovascular invasion, and taxane chemotherapy were predicted to lower RCB score by 0,058, 0,781, dan 0,594, respectively.  expression associated with pCR-RCB class I (p=0,048), but CPS score was not a predictor of RCB score in linear regression analysis. CONSLUSION: sTIL intensity was an independent predictor of breast cancer response to neoadjuvant therapy in RSCM.  expression associated with pCR-RCB class I, but CPS score was not a predictor of RCB score.

Correlation of Before and After Invasive Breast Cancer Neoadjuvant Chemotherapy for NFkB, Cyclin D1, and Survivin Expression.

Background & Objective: Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) therapy need biomarkers to track their progress. Because of the relationship between NFkB, Survivin, and Cyclin D1 with NC resistance, the different expression levels of each of these biomarkers can be different between pre- and post-NC in IBC. However, no research has examined the correlation between these biomarkers before and after the NC expression. This study aimed to determine the correlation among them. Methods: Biomarkers expression (low and high) was used to classify 30 samples. ER, PR, HER2, Ki-67 status, tumor grade, age, and NC response were assessed. The amounts of Survivin, Cyclin D1, and NFkB were evaluated using immunohistochemistry, and the samples were classified based on the cut-off. Chi-square and linear regression were used to evaluate the data. Results: No significant association was found with the changes in the expression of Survivin, Cyclin D1, and NFkB, both before and after the NC. Significant moderate correlations were shown between before and after the NC Survivin expression (r = 0.513) and Cyclin D1 expression (r = 0.543). The correlation between expression of NFkB before and after the NC was not significant. Conclusion: The high potential of these proteins as prognostic indicators was demonstrated by the strong positive association between the expression of Survivin and Cyclin D1 before and after the NC. This upregulation of biomarkers indicates chemoresistance in developing IBC in the presence of NC.

The Potential of Expression of Cyclin-D1 on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma.

BACKGROUND: Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) need indicators to track their progress during treatment. The goal of this research is to learn how cyclin D1 works in conjunction with taxane and non-taxane therapy for people with IBC. METHODS: There were 31 examples divided into two groups, based on: those using a different type of NC (taxane- or non-taxane-based), and NC administration time (before or after). Tumor grade, age, PR, ER, Ki-67, HER2, and Cyclin D1 expression were among the factors considered. Using immunohistochemical labeling, we were able to categorize cyclin D1 levels according to a threshold value, and we supplemented this with data we found in our databases. To analyze the data, we used a modified linear model. RESULTS: The expression of Cyclin D1 decreased after NC delivery (p=0.086). Cyclin D1 expression was reduced in the taxane group (p=0.792). The non-taxane group also saw no differences in outcomes (p = 0.065). There was a larger decrease in Cyclin D1 expression in the non-taxane group compared to the taxane group, but the difference was not statistically significant (p=0.200). CONCLUSION: Cyclin D1 expression, even if the differences are not statistically significant, may be a prognostic indicator of NC reaction in IBC. The involvement of Cyclin D1 in NC warrants more research with bigger IBC sample sizes.

Exploring the Integrated Role of AKT2, CD44v6, And MT1-MMP as Predictors of Axillary Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type.

Background & Objective: Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer, which mainly causes axillary lymph-node metastasis (ALNM). Building on our previous research, we wanted to explore the optimal combination of AKT2, CD44v6, and MT1-MMP for the ALNM prediction. Methods: The presence or absence of ALNM was used to separate 46 paraffin blocks containing IBC-NST primary tumors into two groups. Age, tumor grade, tumor size, receptor status (ER, PR, HER2, Ki-67, TOP2A), and test biomarker expression were evaluated. Biomarker expressions were assessed by IHC staining and categorized according to their respective cut-offs from our previous study, while other data were collected from archives. Data was gathered and analyzed using univariate, multivariate, and AUROC models. Results: The expression of CD44v6 (OR: 12.77, 95% CI: 2.18-87.12, P=0.005) was identified as the independent variable for ALNM. Meanwhile, AKT2 expression (OR: 3.22, 95% CI: 0.36-22.41, P=0.237) and MT1-MMP expression (OR: 5.35, 95% CI: 0.83-34.54, P=0.078) did not demonstrate a statistically significant independent association in respect to ALNM. Combining AKT2 and MT1-MMP on CD44v6 increased overall accuracy by 4% compared to CD44v6 alone (AUROC 0.89 vs. 0.85). Conclusion: The combined usage of AKT2, CD44v6, and MT1-MMP revealed no significant change compared to CD44v6 alone. Due to the cost and practicality, we propose using CD44v6 as a predictor biomarker of ALNM in IBC-NST.

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.

Pilot Study on the Effect of a Single Topical Application of Trichloroacetic Acid 85% on Normal Cervical Tissue.

Background: Early detection and treatment of cervical intraepithelial neoplasia (CIN) through a "see and treat" approach is a pillar of cervical cancer prevention programs in developing countries such as Indonesia. One of the major challenges faced is the limited N2O or CO2 gas supply for cryotherapy. Thus, an alternative therapeutic method such as trichloroacetic acid (TCA) topical application is needed as an alternative solution. The effectiveness of this therapy will depend on its destructive effect on eliminating the whole lesion in CIN. Objective: To estimate the extent of damage in the normal cervical tissue after a single topical application of 85% TCA solution. Design and Methods: This research was an intervention study carried out by applying ±5 ml of 85% TCA solution into the cervix of 40 patients scheduled for total hysterectomy for indications other than cervical pathology 24 h before surgery. The extent of tissue destruction was determined microscopically using histopathological specimens. The study protocol is registered at www.clinicaltrial.gov (ID NCT04911075). Results: In the final analysis, 39 subjects were included. The necrotic area was detected at the superficial layer, accompanied by the full epithelial erosion thickness. In addition, there were also fibrotic areas resembling burned tissue in the stroma. The mean depth of destruction was 1.16 ± 0.01 mm in the anterior lip and 1.01 ± 0.06 mm in the posterior lip. There was no significant depth difference between the anterior and posterior lips (p ≥0.05). Moreover, the 85% TCA topical application was tolerable, as represented by the fact that the vast majority (82.1%) of participants experienced pain with a visual analog scale score of <4. Conclusion: Single dose of TCA 85% in topical solution was able to destroy the normal cervical tissue with a deeper mean depth than the mean depth of CIN III in squamous epithelium.

Histopathological discrepancy and variation of surgical management in mucinous ovarian cystadenoma and pseudomyxoma peritonei.

INTRODUCTION AND IMPORTANCE: Mucinous cystadenoma occurs in 10-15% of all ovarian tumors. Diagnosis and treatment should be decided precisely as it has a chance to develop into pseudomyxoma peritonei (PMP). Management of PMP might be challenging especially when repeated surgery is needed. CASE PRESENTATION: The first case, a 22-year-old lady with recurrent stomach enlargement for seven months. She had history of laparotomy surgery due to an ovarian tumor. Whole abdomen contrast CT scan showed a large cyst with mucinous fluid. We decided to do re-laparotomy and found a left ovarian cyst. Histological examination results confirm ovarian mucinous cystadenoma. The second case was, 55-year-old woman, with abdominal enlargement for six months. She had a history of laparotomy and chemotherapy due to pseudomyxoma peritonei. Post chemotherapy MRI showed persistent pseudomyxoma and two multilocular cysts from both adnexa. Debulking laparotomy was then conducted. We obtained 8 L of mucinous pseudomyxoma along with mucinous cyst from both ovaries. The final diagnosis concluded as a pseudomyxoma and we decide to close the follow-up of the patient. CLINICAL DISCUSSION: Pseudomyxoma is caused by the production of mucin originating from intra-abdominal organs. Open surgery should be prioritized when the mucinous cystadenoma is detected to do a complete peritoneum evaluation and avoid perioperatively ruptured mucinous neoplasm. Pseudomyxoma often needed repeated surgical treatment and may exhibit different surgical findings and different pathologies. CONCLUSION: Repeated surgery is logical and still no need for adjuvant chemotherapy in both cases. Accurate and precise diagnosis should be prioritized in order to prevent repeated surgery.

Expression of CD44+/CD24-, RAD6 and DDB2 on chemotherapy response in ovarian Cancer: A prospective flow cytometry study.

Backgrounds: Ovarian cancer is the 8th deadliest common cancer in women around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. Chemoresistant cancer cells have characteristic expressions of cancer stem cell proteins (CSCs) CD44+/CD24-, RAD6 and DDB2. The increased expression of CD44+/CD24-, RAD6, and decreased DDB2 are believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. Thus, this study's objective is to analyze the correlation between the expression of CD44+/CD24-, RAD6 and DDB2 with ovarian cancer chemoresistance. Materials and methods: This study was conducted with a prospective cohort of 64 patients who is divided into two groups (32 patients in each group) at the Obstetrics-gynecology and pathology department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All suspected ovarian cancer patients underwent cytoreductive debulking and histopathological examination. Chemotherapy was given for six series followed by six months of observation. After the observation, we determined the therapy's response with the RECIST Criteria (Response Criteria in Solid Tumors) and then classified the results into chemoresistant or chemosensitive groups. Flow cytometry blood tests were then performed to examine the expression of CD44+/CD24-, RAD6 and DDB2. Results: There was a significant relationship between increased levels of CD44+/CD24-, and RAD6 (p < 0.05) levels with the chemoresistance of ovarian cancer. The logistic regression test showed that the CD44+/CD24- was better marker. Conclusions: These results indicate that CD44+/CD24 and RAD6 expressions are significantly associated with ovarian cancer chemoresistance, and CD44+/CD24- is the better marker to predict ovarian cancer chemoresistance.

CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type.

BACKGROUND: Invasive breast carcinoma of no special type (IBC-NST) is the most widespread invasive carcinoma subtype causing primarily regional metastases of the lymphatic node (LNM). The capacity of CD44 variant exon 6 (CD44v6) expression as an LNM predictor biomarker in IBC-NST was explored. METHODS: We conducted a cross-sectional research with 48 paraffin blocks containing IBC-NST primary tumors that were divided into two groups by LNM. The assessment has been carried out in terms of age, tumor size, tumor grade, lymphovascular invasion (LVI), and CD44v6 expression. The expression of CD44v6 was analyzed on the grounds of immunohistochemical (IHC) staining, while other data were taken from archives. Statistical analysis is carried out by univariate, multivariate, and AUROC. RESULTS: CD44v6 exhibits a dominant expression in IBC-NST tumor cells. Univariate analysis revealed a significant association between CD44v6 and LNM status (p = 0.001). Multiple logistic regression results showed that CD44v6 expression and LVI were significantly associated with LNM with OR 10.7 (95% CI: 2.43 to 47.08) and 6.22 (95% CI: 1.4 to 27.88), respectively. CD44v6 expression was able to discriminate against LNM with AUROC 0.863 ± 0.053 (95% CI: 0.759 to 0.967) at the H-score cut-off 133.889 (75% sensitivity and 83.3% specificity). CONCLUSION: CD44v6 expression and LVI are potential predictors of LNM in IBC-NST. The H-score cut-off of the CD44v6 expression can also be used as a threshold for classification in further investigation.

Correlation between CD 34 and CD 68 expression in placental malaria with maternal anemia.

BACKGROUND: Malaria is the second most life-threatening infectious disease in Indonesia, causing approximately 1-3 million deaths annually. Histopathologic studies assessing CD 68 and CD 34 protein expression in placental malaria and its association with maternal anemia are essential to determine the prognosis of malaria in pregnancy. MATERIALS AND METHODS: This cross-sectional study was carried out in 2017. Thirty biopsy samples of human placental tissue were obtained from Timika and Sumba, and ten normal biopsy samples were taken from the Pathological Anatomy Department of Cipto Mangunkusumo General Hospital as comparisons. CD 34 and CD 68 protein expressions were determined using immunohistochemistry, and the resulting data were analyzed using SPSS. RESULTS: Average hemoglobin (Hb) level was 9.5 mg/dL, 11.5 mg/dL, and 9.9 mg/dL in acute infection, chronic infection, and latent infection, respectively. A positive correlation was found between CD 68 protein expression and maternal Hb level. No correlation was found between CD34 expression and maternal anemia. CONCLUSIONS: CD 68 expression in placental tissue biopsy from Timika and Sumba residents with placental malaria was shown to be positively correlated with maternal anemia. Immunohistochemical examination of CD 68 may play a role in the early diagnosis of malaria.

Adult granulosa cell tumor with minor foci of juvenile granulosa cell tumor in postmenopausal woman: A rare case report.

INTRODUCTION: Granulosa cell tumor (GCT) is a rare neoplasm that is divided into adult GCT (AGCT) and juvenile GCT (JGCT). Generally, a patient will only have the AGCT or JGCT subtypes. Here, we presented the first case of AGTC accompanied by focal JGTC in a postmenopausal woman. PRESENTATION OF CASE: A 63-year-old postmenopausal woman came with distended abdomen accompanied by postmenopausal bleeding. CT scan shows a solid mass with cystic degeneration. Laparotomy found a solid mass from the right ovary measuring 18 × 15 × 14 cm. The pathological results showed a diffuse tumor representing AGCT, accompanied by Call-Exner bodies and nuclear groove. In addition, minor foci were also found, which consist of well-defined margins tumor and follicular-like structures that resemble JGCT. The patient underwent bilateral salpingo-oophorectomy with a total hysterectomy and no recurrence in three months follow-up. DISCUSSION: Age and clinical symptoms cannot be used as specific differentiators between AGTC and JGTC. Radiological imaging also shows a similar appearance of solid masses tumors with hemorrhagic or fibrotic changes, multilocular cystic lesions, or completely cystic tumors. The concomitant findings of JGCT and AGCT could be distinguished very carefully by anatomical pathology examination. It is crucial to differentiate AGCT from JGCT, especially to see the prognosis. CONCLUSION: The role of pathologists is needed in differentiating AGCT and JGCT, primarily when found simultaneously.

Melatonin effect on hypoxia inducible factor-1α and clinical response in patients with oral squamous cell carcinoma receiving neoadjuvant chemotherapy: A randomized controlled trial.

CONTEXT: Chemoresistance is a major issue in patients with locally advanced oral squamous cell carcinoma (OSCC). In this study, we evaluated the effectiveness of melatonin in conjunction with neoadjuvant chemotherapy (NC) on hypoxia-inducible factor-1α (HIF-1α) expression and clinical response in locally advanced OSCC patients. AIMS: To study the effects of melatonin on HIF-1α expression and its effect on the clinical response of patients with locally advanced OSCC. SETTINGS AND DESIGN: A randomized controlled trial was conducted, wherein patients were recruited from several hospitals in Jakarta, Indonesia. Patients were randomized into two groups using computerized block randomization. SUBJECTS AND METHODS: Both groups were given NC, with treatment group receiving melatonin. Outcomes measured in this study were HIF-1α expression from tissue samples and clinical response based on the RECIST 1.1 criteria. Twenty-five patients completed the study protocol and were included in the data analysis. STATISTICAL ANALYSIS USED: Shapiro-Wilk test was used to test the data normality. For data with normal distribution, we conducted an independent t-test to compare between the two groups. Data with abnormal distribution were analyzed using Mann-Whitney U-test. The mean difference between the two groups was analyzed using Shapiro-Wilk normality test. RESULTS: Our study showed a significant decrease in HIF-1α expression in the melatonin group compared to the placebo group (P < 0.05, relative risk 3.08). However, the degree of reduction of HIF-1α expression in the melatonin group did not differ significantly (P = 0.301). CONCLUSIONS: Our study showed that melatonin administered at 20 mg/day could reduce the expression of HIF-1α and residual tumor percentage, but did not affect the clinical response in OSCC patients.

Massive obstetric haemorrhage on post caesarean subtotal hysterectomy due to late detection of occult placenta percreta: A case report.

INTRODUCTION: Placenta accreta syndrome is a significant cause of maternal mortality and morbidity. Therefore, a multidiscipline approach is essential to overcome this life-threatening disorder for the mother and fetus. PRESENTATION OF CASE: A 32-year-old women gravida 3 parity 2, 34 weeks gestation come due to recurrent antepartum haemorrhage. She had twice prior caesarean section. Ultrasound assessment suggests total placenta previa and elevating suspicion to placenta accreta. However, intraoperatively its sign is unavailable. Although we have done subtotal hysterectomy, massive bleeding still occurring. Therefore, we present management of unexpected placenta percreta. DISCUSSION: Management of unexpected placenta percreta involves prenatal diagnosis, haemoglobin optimization, surgical management anticipating haemorrhage, dedicated maternal ICU, blood bank providing massive transfusion and blood component. CONCLUSION: Close monitoring is important in catastrophe management of Placenta Accreta Syndrome.

Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type.

BACKGROUND: Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer and mainly causes regional lymph-node metastasis (LNM). We investigated the potential for AKT2 expression as a predictive biomarker for LNM in IBC-NST. METHODS: Forty-eight paraffin blocks containing IBC-NST primary tumors were divided into two groups based on presence or absence of LNM. Age, tumor grade, tumor size, lymphovascular invasion (LVI), and AKT expression were assessed. AKT2 expression was assessed based on immunohistochemical staining, while other data were collected from archives. RESULTS: Multiple logistic regression results showed that AKT2 expression and LVI were significantly associated with LNM (odds ratio [OR], 5.32; 95% confidence interval [CI], 1.42 to 19.93 and OR, 4.46; 95% CI, 1.17 to 16.97, respectively). AKT2 expression was able to discriminate against LNM (area under the receiver operating characteristic, 0.799 ± 0.063; 95% CI, 0.676 to 0.921) at an H-score cutoff of 104.62 (83.3% sensitivity, 62.5% specificity). CONCLUSIONS: AKT2 expression has potential as a predictor of LNM in IBC-NST. The H-score cutoff for AKT2 expression can be used as a classification guide in future studies.

Transverse vaginal septum managed by simple flap surgery technique: A case report.

BACKGROUND: Transverse Vaginal Septum (TVS) is a rare congenital abnormality, classified as the Mullerian duct anomaly development.1,2 TVS incidence range from 1:2.000 to 1:72.000. Management of TVS may only requirement local excision with a simple end to end anastomosis of the vagina, and use of skin grafts, but this technique has been reported has common complications of secondary tissue contracture, which often lead to stenosis of the vagina.3 In this case we managed TVS with simple flap technique to avoid such postoperative complications and maintain caliber of vagina. CASE: A 11 years old girl complained cyclical abdominal pain since a year ago without history of menstrual blood. Patient already had vaginal surgery for removing menstrual blood, but after vaginal surgery the menstrual blood cannot be removed, then referred to our hospital. Ultrasound examination revealed hematometra and hemocolpos. The septum location was 3,38 cm proximal distance from vaginal introitus with the thickness of 8.1 mm. We performed simple excision of the septum with formerly performed distal vaginal septum mucosa preparation creating lateral flaps, then approximating the flaps to the edge of the proximal vaginal mucosa with interrupted suture continued with hymenorraphy. The patient has no complaint 6 months after surgery with vaginal length 8 cm, and had regular menstrual cycle. CONCLUSION: A simple flap surgery technique can be done in transverse vaginal septum, with no complication such as tissue contracture, vaginal stenosis, or insightly scarring. This is a simple technique and can be done with hymenorraphy to restore normal anatomy of hymen.

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.

Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial.

Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced-stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF-κB levels] effects, apoptotic index, and safety of Biocurcumin (BCM-95) as a radiosensitiser in cervical cancer. In this double-blind placebo randomised-controlled trial, we randomised 121 patients into 2 groups (BCM-95 or placebo). MDA and their NF-κB levels and apoptotic index were measured before and after administering 24 Gy of radiation. MDA was identified using Wills' method, whereas NF-κB was identified via ELISA. The apoptotic index was identified using TUNEL and DAPI staining. The clinical response was classified based on the RECIST. MDA levels before radiation were similar between both groups in per protocol and intention-to-treat (ITT) analyses (p = 0.53 and p = 0.16, respectively). After radiation, MDA levels increased in both groups with no significant differences in per protocol and ITT analyses (p = 0.52 and p = 0.18, respectively). NF-κB levels before radiation were similar between the two groups in per protocol and ITT analyses (p = 0.92 and p = 0.98, respectively). After radiation, the BCM-95 group showed an increase in the NF-κB levels compared with the placebo group in per protocol analysis but not in ITT analysis (p = 0.018 and p = 0.42, respectively). The BCM-95 group had a higher apoptotic index before radiation in per protocol analysis but not in ITT analysis (p = 0.01 and p = 0.61, respectively). After radiation, the apoptotic index remained higher in the BCM-95 group in per protocol analysis but not in ITT analysis (p = 0.04 and p = 0.91, respectively). There was no significant difference in complete response between the groups (per protocol, p = 0.61; ITT analysis, p = 0.90). Although BCM-95 can regulate ROS, NF-κB, and apoptosis in human cervical cancer, it is not significant. Therefore, BCM-95 does not improve clinical response to radiation treatment.

Effect of melatonin supplementation in combination with neoadjuvant chemotherapy to miR-210 and CD44 expression and clinical response improvement in locally advanced oral squamous cell carcinoma: a randomized controlled trial.

BACKGROUND: Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment. It is thought that neoadjuvant chemotherapy (NC) in locally advanced OSCC is able to shrink tumor size. Chemoresistancy is a problem due to hypoxic microenvironment characterized by increased expression of HIF-1α. It is also regulated by miR-210 as well as increased expression of CD44 and CD133. Melatonin has a powerful antioxidant and oncostatic effects that are expected to improve tumor hypoxia and clinical response. Fifty patients with OSCC were included and randomized. miR-210 and CD44 expression were measured before and after intervention using qRT-PCR absolute quantification, and clinical response was evaluated according to RECIST 1.1 criteria. This study aims to determine the effect of melatonin in improving the clinical response of patients with locally advanced oral squamous cell carcinoma (OSCC) after neoadjuvant chemotherapy to miR-210 and CD44 expression. RESULTS: Melatonin administration reduced miR-210 levels but not significant (p = 0.767). CD44 expression also decreased in the melatonin group compared with placebo yet was not significant (p = 0.103). There was a decrease in the expression of miR-210 and CD44 followed by a decrease in the percentage of residual tumor but not significant (p = 0.114). CONCLUSION: In OSCC, the addition of 20-mg melatonin to neoadjuvant chemotherapy (NC) reduced the expression of miR-210 and CD44 and decreased the percentage of tumor residue; however, no statistically significant result was observed. TRIAL REGISTRATION: This study is registered to ClinicalTrials.gov under trial registration number: NCT04137627 with date of registration on October 22, 2019-retrospectively registered, accessible from: https://clinicaltrials.gov/ct2/show/NCT04137627.