Elevated serum soluble programmed death ligand 1 (sPD-L1) level correlate with clinical characteristics in breast cancer patients: A study at Hospital Universiti Sains Malaysia.

BACKGROUND: Elevated serum levels of soluble PD-L1 (sPD-L1) have been reported in many cancers; however, there is limited data of sPD-L1 in breast cancer, especially those representing Asian (Malay) women. The purpose of this study was to evaluate sPD-L1 serum levels and analyze its correlation with clinical characteristics in breast cancer patients at Hospital Universiti Sains Malaysia (HUSM). METHODS: Blood specimens were obtained from 92 malignant, 16 benign breast cancer patients and 23 healthy controls. The serum concentrations of sPD-L1 were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The median serum sPD-L1 concentration of malignant and benign breast cancer patients was significantly elevated compared to the healthy cohorts (12.50 ng/mL vs 13.97 ng/mL vs 8.75 ng/mL, p < 0.05). Optimal cut-off value of serum sPD-L1 for predicting disease progression was 8.84  ng/mL. Elevated serum sPD-L1 levels were significantly associated with menarche age, ethnicity, birth control usage, comorbidity and HER2 status (p < 0.05). Multivariate analysis showed the menarche age and birth control were the independent factors affecting sPD-L1 expression. CONCLUSION: Elevated serum levels of sPD-L1 were significantly associated with several clinical characteristics and warrant further investigation in evaluating patients pre-diagnosed with breast cancer.

Binasal Field Defect in Non-arteritic Anterior Ischemic Optic Neuropathy.

Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of optic neuropathy in older adults and is usually associated with an altitudinal visual field defect. Binasal hemianopia is a rare visual field presentation, and most causes are due to ocular pathology instead of brain pathology. It is an infrequent finding in NAION. We report a rare presentation of binasal hemianopia visual field defect in a patient with NAION. This a case of an elderly lady with underlying uncontrolled type 2 diabetes mellitus, hypertension, and dyslipidemia who presented with a sudden onset of painless blurring of vision in the left eye. She had a similar episode of blurred vision involving the other eye two years ago. Her visual acuity was reduced in both eyes. Humphrey visual field showed a binasal field defect. Fundoscopy showed mild hyperemic optic disc swelling in the left eye and a pale disc in the right eye. The CT scan and MRI were normal. She was co-managed with the medical team to control her systemic risk factors. Although NAION is the most common cause of optic neuropathy in older adults, binasal hemianopia is a rare visual field presentation in NAION. The history and assessment from this case add important information toward diagnosing NAION.

Carcinosarcoma: A Rare and Aggressive Breast Tumor in a Young Lady.

Carcinosarcoma of the breast is a subtype of metaplastic breast carcinoma characterized by differentiation of the neoplastic epithelium toward mesenchymal-looking elements. It is a highly aggressive rare subtype of invasive breast neoplasm that exhibits a distinct histologic entity. Only a limited number of reports related to this type of disease have been reported. Here, we present a case of breast carcinosarcoma in a lady in her early 20s, which is relatively young among all cases published. It was challenging to achieve diagnosis preoperatively with histopathological evaluation of the ultrasound-guided tru-cut biopsy sample. With no evidence of distant metastasis clinically and radiologically, a surgical option was opted for. Left mastectomy and left chest wall reconstruction with deep inferior epigastric artery free flap were performed. Post-excision specimen was confirmed to be carcinosarcoma.

Developing a Supplementary Diagnostic Tool for Breast Cancer Risk Estimation Using Ensemble Transfer Learning.

Breast cancer is the most prevalent cancer worldwide. Thus, it is necessary to improve the efficiency of the medical workflow of the disease. Therefore, this study aims to develop a supplementary diagnostic tool for radiologists using ensemble transfer learning and digital mammograms. The digital mammograms and their associated information were collected from the department of radiology and pathology at Hospital Universiti Sains Malaysia. Thirteen pre-trained networks were selected and tested in this study. ResNet101V2 and ResNet152 had the highest mean PR-AUC, MobileNetV3Small and ResNet152 had the highest mean precision, ResNet101 had the highest mean F1 score, and ResNet152 and ResNet152V2 had the highest mean Youden J index. Subsequently, three ensemble models were developed using the top three pre-trained networks whose ranking was based on PR-AUC values, precision, and F1 scores. The final ensemble model, which consisted of Resnet101, Resnet152, and ResNet50V2, had a mean precision value, F1 score, and Youden J index of 0.82, 0.68, and 0.12, respectively. Additionally, the final model demonstrated balanced performance across mammographic density. In conclusion, this study demonstrates the good performance of ensemble transfer learning and digital mammograms in breast cancer risk estimation. This model can be utilised as a supplementary diagnostic tool for radiologists, thus reducing their workloads and further improving the medical workflow in the screening and diagnosis of breast cancer.

Over-the-Counter Breast Cancer Classification Using Machine Learning and Patient Registration Records.

This study aims to determine the feasibility of machine learning (ML) and patient registration record to be utilised to develop an over-the-counter (OTC) screening model for breast cancer risk estimation. Data were retrospectively collected from women who came to the Hospital Universiti Sains Malaysia, Malaysia for breast-related problems. Eight ML models were used: k-nearest neighbour (kNN), elastic-net logistic regression, multivariate adaptive regression splines, artificial neural network, partial least square, random forest, support vector machine (SVM), and extreme gradient boosting. Features utilised for the development of the screening models were limited to information in the patient registration form. The final model was evaluated in terms of performance across a mammographic density. Additionally, the feature importance of the final model was assessed using the model agnostic approach. kNN had the highest Youden J index, precision, and PR-AUC, while SVM had the highest F2 score. The kNN model was selected as the final model. The model had a balanced performance in terms of sensitivity, specificity, and PR-AUC across the mammographic density groups. The most important feature was the age at examination. In conclusion, this study showed that ML and patient registration information are feasible to be used as the OTC screening model for breast cancer.

Changes in Spinal Alignment of Women Who Underwent Unilateral Mastectomy with Immediate Autologous Breast Reconstruction Compared To Mastectomy without Breast Reconstruction.

INTRODUCTION: The impact of breast reconstruction on spinal alignment is not well studied, especially in immediate autologous breast reconstruction. Studies on body posture have shown greater asymmetry among those without reconstruction. This study compared the changes in spinal alignment pre- and post-operatively among women who underwent unilateral mastectomy without reconstruction (MA) versus immediate autologous breast reconstruction (IABR). METHODS: A cross sectional, retrospective study analysed MA and IABRs performed from January 2007 to December 2017 and their pre- and post-operative anterior chest radiographs. The change in Cobb's angle (degrees) less than 1 year, 1 to 2 years, more than 2 years post-operatively were analysed using GE Healthcare Centricity Picture Archive and Communications Systems. RESULTS: 537 patients underwent mastectomy; 76 fulfilled the inclusion criteria (36 IABR, 40 MA). No significant difference existed between mean pre- and post-operative Cobb's angle change across all 3 groups, less than 1 year (MA 3.57±3.84, IABR 3.316±2.72, p=0.81), 1 to 2 years (MA 1.84±4.81, IABR -2.68±3.21, p=0.577) and more than 2 years post-operatively (MA -1.14±5.30, IABR -0.94±5.10, p=0.898). However raw data indicated IABR improved spinal alignment in the short and intermediate period post-operatively. Among IABR, free flap breast reconstruction improved spinal alignment compared to pedicled flaps [free flaps: 2.21±3.28, pedicled flaps: 0.01±3.67 (p=0.027)]. CONCLUSION: IABR has a positive impact on spinal alignment in early and intermediate post-operative period compared to MA, especially in women with larger breast volume. Physical benefits of IABR should be highlighted to improve patient's access to breast reconstruction globally.

Bilateral Optic Perineuritis in Tuberculosis-Immune Reconstitution Inflammatory Syndrome.

Optic perineuritis (OPN) in pulmonary tuberculosis (PTB) patients while on anti-tuberculous treatment is rare. It may occur due to tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS). Visual prognosis is poor if not treated early. We report a rare case of bilateral OPN in an elderly patient on treatment for PTB. A 79-year-old Malay man presented with a painless bilateral blurring of vision for three weeks. He was diagnosed to have PTB and has been on anti-tuberculous treatment for five months. Visual acuity in both eyes was only counting fingers. Optic nerve function tests were significantly reduced bilaterally. Fundoscopy showed bilateral segmental temporal optic disc pallor. Both visual field assessments were constricted. Other infective screenings and tumor markers were negative. Neuro-imaging revealed bilateral OPN involving the intraorbital segment. High-dose intravenous corticosteroid therapy was commenced, followed by slow tapering of oral prednisolone. Anti-tuberculous treatment was continued for a total course of nine months. The left visual acuity improved to 3/60. However, the right eye vision remained poor. His general condition was good.

Factors Influencing Mammographic Density in Asian Women: A Retrospective Cohort Study in the Northeast Region of Peninsular Malaysia.

Mammographic density is a significant risk factor for breast cancer. In this study, we identified the risk factors of mammographic density in Asian women and quantified the impact of breast density on the severity of breast cancer. We collected data from Hospital Universiti Sains Malaysia, a research- and university-based hospital located in Kelantan, Malaysia. Multivariable logistic regression was performed to analyse the data. Five significant factors were found to be associated with mammographic density: age (OR: 0.94; 95% CI: 0.92, 0.96), number of children (OR: 0.88; 95% CI: 0.81, 0.96), body mass index (OR: 0.88; 95% CI: 0.85, 0.92), menopause status (yes vs. no, OR: 0.59; 95% CI: 0.42, 0.82), and BI-RADS classification (2 vs. 1, OR: 1.87; 95% CI: 1.22, 2.84; 3 vs. 1, OR: 3.25; 95% CI: 1.86, 5.66; 4 vs. 1, OR: 3.75; 95% CI: 1.88, 7.46; 5 vs. 1, OR: 2.46; 95% CI: 1.21, 5.02; 6 vs. 1, OR: 2.50; 95% CI: 0.65, 9.56). Similarly, the average predicted probabilities were higher among BI-RADS 3 and 4 classified women. Understanding mammographic density and its influencing factors aids in accurately assessing and screening dense breast women.

A Five-Year Review of the Outcomes of Breast Imaging Reporting and Data System 4 Lesions in Hospital Universiti Sains Malaysia.

PURPOSE: The Breast Imaging Reporting and Data System (BI-RADS) lexicon used in reporting breast imaging has several categories with specific positive predictive values for breast cancer. Among those, BI-RADS 4 is associated with a wider range of risk for breast cancer, which makes the decision for biopsy difficult. The study aim was to determine the malignancy rate and clinical outcomes of BI-RADS 4 lesions in Hospital Universiti Sains Malaysia (HUSM) for a period of five years. METHODS: This was a retrospective study of patients diagnosed by mammographic or ultrasonographic findings with BI-RADS 4 breast lesions in HUSM, Kelantan from July 2015 to June 2020. Data were collected from the medical records and an electronic database. Patients with BI-RADS 4 lesions who underwent biopsy and had a known tissue diagnosis were included in this study. The data was used to calculate the malignancy rate and associated positive predictive factors for breast cancer associated with BI-RADS 4 lesions. RESULTS: From the mammography and ultrasonography performed at HUSM from July 2015 to June 2020, a total of 256 lesions were categorized as BI-RADS 4. However, only 198 BI-RADS 4 lesions underwent biopsy and were included in the study. Of these 198 lesions, 26.8% were malignant on histopathological examination of the biopsy samples. Simple logistic regression analysis showed that age, diabetes mellitus, hypertension, number of parity, and certain mammogram findings were significantly associated with breast cancer. Invasive breast cancer was the most common type. Fibrocystic disease was the most common benign pathology, followed by fibroadenoma. CONCLUSION: The malignancy rate of BI-RADS 4 lesions in HUSM was similar to previously reported rates. A thorough evaluation of positive predictive factors and careful selection of patients for biopsy in BI-RADS 4 lesions will minimize unwanted biopsies and associated patient anxiety, in addition to reducing the health care burden.

Prognostic prospect of soluble programmed cell death ligand-1 in cancer management.

Aggressive tissue biopsy is commonly unavoidable in the management of most suspected tumor cases to conclusively verify the presence of cancerous cells through histological assessment. The extracted tissue is also immunostained for detection of antigens (tissue tumor markers) of potential prognostic or therapeutic importance to assist in treatment decision. Although liquid biopsies can be a powerful tool for monitoring treatment response, they are still excluded from standard cancer diagnostics, and their utility is still being debated in the scientific community. With a myriad of soluble tissue tumor markers now being discovered, liquid biopsies could completely change the current paradigms of cancer management. Recently, soluble programmed cell death ligand-1 (sPD-L1), which is found in the peripheral blood, i.e. serum and plasma, has shown potential as a pre-therapeutic predictive marker as well as a prognostic biomarker to monitor treatment efficacy. Thus, this review focuses on the emergence of sPD-L1 and promising technologies for its detection in order to support liquid biopsies for future cancer management.

Asymptomatic complete distal abdominal aortic occlusion with initial presentation of ruptured intracranial aneurysm.

Aortoilliac occlusive disease is occlusive atherosclerosis disease involving the distal aorta and bifurcation of iliac arteries and it is a subtype of peripheral arterial disease. Total occlusion of the abdominal aorta is a rare occurrence with an incidence of 3% -8.5% among the aortoiliac occlusive disease patients. We present a case of a 53 years old patient with a background history of hypertension and ex intravenous drug abuser with negative retroviral screening status, with no previous complaints who was brought to the Emergency Department with sudden onset of altered sensorium and 1 episode of seizure. Computed tomography angiogram of the brain showed a ruptured anterior communicating artery aneurysm. Diagnostic conventional angiogram of the brain was planned; however, difficulty was encountered during bilateral femoral artery cannulation with the abrupt termination of bilateral common iliac arteries. Computed tomography angiogram of the abdomen showed incidental finding of total occlusion of the abdominal aorta. As a conclusion, total occlusion of abdominal aorta secondary to aortoiliac occlusive disease with an associated intracranial aneurysm is never reported in the literature to date. This case highlights the possibility of association in between these two conditions which may benefit from further research.

Plasma Circulating Mirnas Profiling for Identification of Potential Breast Cancer Early Detection Biomarkers.

OBJECTIVE: This study aimed to characterize the miRNA expression profiles from plasma samples of our local breast cancer patients in comparison to healthy control by using miRNA PCR Array. METHODS: In this study, plasma miRNA profiles from eight early-stage breast cancer patients and nine age-matched (± 2 years) healthy controls were characterized by miRNA array-based approach, followed by differential gene expression analysis, Independent T-test and construction of Receiver Operating Characteristic (ROC) curve to determine the capability of the assays to discriminate between breast cancer and the healthy control. RESULTS: Based on the 372-miRNAs microarray profiling, a set of 40 differential miRNAs was extracted regarding to the fold change value at 2 and above. We further sub grouped 40 miRNAs of breast cancer patients that were significantly expressed at 2-fold change and higher. In this set, we discovered that 24 miRNAs were significantly upregulated and 16 miRNAs were significantly downregulated in breast cancer patients, as compared to the miRNA expression of healthy subjects. ROC curve analysis revealed that seven miRNAs (miR-125b-5p, miR-142-3p, miR-145-5p, miR-193a-5p, miR-27b-3p, miR-22-5p and miR-423-5p) had area under curve (AUC) value > 0.7 (AUC p-value < 0.05). Overlapping findings from differential gene expression analysis, ROC analysis, and Independent T-Test resulted in three miRNAs (miR-27b-3p, miR-22-5p, miR-145-5p). Cohen's effect size for these three miRNAs was large with d value are more than 0.95. CONCLUSION: miR-27b-3p, miR-22-5p, miR-145-5p could be potential biomarkers to distinguish breast cancer patients from healthy controls. A validation study for these three miRNAs in an external set of samples is ongoing.
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Sexual Dysfunction Among Women With Breast Cancer in the Northeastern Part of West Malaysia.

INTRODUCTION: Female sexual dysfunction (FSD) is a common complication among breast cancer patients following treatment. AIM: To assess the prevalence and factors associated with FSD among breast cancer patients in Kelantan. METHODS: This cross-sectional study recruited female patients, aged 18-65, who were married and sexually active with their partner, diagnosed with breast cancer, and had undergone breast surgery. Those with underlying psychiatry disorders, previous pelvic surgery, and husbands with sexual problems were excluded. The questionnaire contained demographic and clinical information, together with the Malay Version of the Breast Impact of Treatment Scale and the Malay Version of Female Sexual Distress Scale-Revised. Their sexual function was evaluated using the Malay Version of the Female Sexual Function Index-6. The data were analyzed with simple and multiple linear regressions. MAIN OUTCOME MEASURES: The prevalence and associated factors for FSD in breast cancer patients. RESULTS: Ninety-four eligible patients were recruited for this study. In total, 73.4% (n = 69) of the patients reported having sexual dysfunction. A family history of breast cancer (P = 0.040), duration of marriage (P = 0.046), and frequency of sexual intercourse (P = 0.002) were significant factors associated with FSD in breast cancer patients after surgery. CONCLUSION: The significant associated factors shown to influence the FSD score include family history of breast cancer, duration of marriage, and frequency of sexual intercourse. About 73.4% of patients have risk of developing FSD after receiving breast cancer treatment. Siang OP, Draman N, Muhamad R, et al. Sexual Dysfunction Among Women With Breast Cancer in the Northeastern Part of West Malaysia. Sex Med 2021;9:100351.

Accuracy of Computed Tomography Attenuation Value of Lumbar Vertebra to Assess Bone Mineral Density.

BACKGROUND: Computed tomography (CT) attenuation (Hounsfield unit [HU]) value of lumbar vertebra may provide an alternative method in the detection of osteoporosis during CT scans. METHODS: A cross-sectional study on 50 patients of age 50 and above with contrast-enhanced CT (CECT) and dual-energy X-ray absorptiometry (DXA) was conducted from November 2018 to November 2019. Single region of interest (ROI) was placed at the anterior trabecular part of L1 vertebra on CECT to obtain HU value. Correlation of CT HU value of L1 vertebra and DXA T-score, interrater reliability agreement between HU value of L1 vertebra and T-score in determining groups of with and without osteoporosis, ROC curve analysis for diagnostic accuracy and cut-off value of CT for detection of osteoporosis were identified. RESULTS: Significant correlation between HU value of L1 vertebra and L1 T-score (r = 0.683)/lowest skeletal T-score (r = 0.703) (P < 0.001). Substantial agreement between HU value of L1 vertebra and DXA in determining the groups with and without osteoporosis (k = 0.8; P < 0.001). The area under the receiver operating characteristic (AUROC) curve was 0.93 (95% CI: 0.86, 1.00) using HU value (P < 0.001). Cut-off value for osteoporosis was 149 HU. CONCLUSION: HU value of lumbar vertebra is an effective alternative for the detection of osteoporosis with high diagnostic accuracy in hospitals without DXA facility.

Author Correction: A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Adult and Pediatric Lateral Lamella Cribriform Plate Height: In Need for a Comparative Study.

Surgery for sinuses has evolved with the advancement of instruments and modification in techniques. Endoscopes have expanded the surgical roles for lesions in the nose and para-nasal sinuses with reduced rate of complications and cosmetic side effects. Nevertheless sinus surgery in pediatrics patients has its own challenges. Pre-operative imaging is of paramount important especially when embarking on skull base procedures. The differences between adult and pediatric anatomy need to be further studied.

A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease.

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75-83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

Tualang honey adjunct with anastrozole improve parenchyma enhancement of breast tissue in breast cancer patients: A randomized controlled trial.

BACKGROUND: To investigate whether the combination of anastrozole and Tualang honey (T honey) influences background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) of postmenopausal women with breast cancer. METHODS: A total of 30 patients were recruited and randomly divided into control (anastrozole 1 mg daily) and intervention (anastrozole 1 mg + T honey 20 g daily). The BPE of the contralateral breast before and six months following treatment was compared using the sign test. RESULTS: There was a decrease in BPE in 10% of the women (p = 0.317) who received only anastrozole, which resulted in a change of BPE category from moderate to mild. However, the combination of anastrozole and T honey evoked a decrease in BPE in 42% of the patients (p = 0.034). CONCLUSIONS: The combination of T honey and anastrozole maybe more efficacious than anastrozole alone in decreasing breast BPE in breast cancer patients. These findings support the medicinal value of T honey as an adjuvant treatment to anastrozole.

Orbital multiple myeloma: a diagnostic challenge.

Orbital involvement in multiple myeloma is unusual. We describe the case of an 85-year-old woman who presented with right eye proptosis, reduced visual acuity and diplopia. Computed tomography showed a lobulated, enhancing soft tissue mass arising from the right greater wing of the sphenoid with intraconal, lacrimal gland and ocular muscle involvement. Histopathology revealed predominantly atypical plasma cells in a background of reactive lymphocytes, with monoclonality towards kappa light chain protein, suggestive of multiple myeloma. This case illustrates the diagnostic imaging challenge of orbital multiple myeloma.