AB034. Medico-legal ethics dilemma in treatment decisions for intracranial metastasis in a young gravida patient: a case report.

BACKGROUND: Advanced cancer cases in pregnant patients present complex medico-legal and ethical challenges. We present a case of advanced leiomyosarcoma during pregnancy and its medico-legal aspect. It aims to provide insights into navigating these issues and improving decision-making frameworks for similar cases. CASE DESCRIPTION: A 22-year-old pregnant female at 18 weeks gestation presented with a complaint of a left thigh mass. The patient experienced continuous moderate-severe pain throughout the left thigh and headache accompanied by vomiting. Physical examination revealed somnolence, eyelid ptosis, and ophthalmoplegia of the left eye. The left femoral exhibited erythema, edema, and restricted range of motion due to pain. Femur magnetic resonance imaging (MRI) revealed a pathological mid-femoral fracture secondary to infiltrative soft tissue mass, with multiple inguinal lymphadenopathy metastases. Brain MRI without contrast identified multiple masses in the right frontal and left temporal regions causing significant intracranial mass effect prompting craniotomy for tumor removal. A needle biopsy of the thigh mass confirmed leiomyosarcoma. The patient's consciousness improved after the surgery but suddenly deteriorated a few days later, brain scan without contrast showed an increased size and mass effect of the left temporal lesion. Whole-brain radiation therapy was initiated, but the patient's condition worsened and the fetus also exhibited intrauterine growth restriction and severe oligohydramnios due to cancer progression. Both the patient and fetus succumbed to the disease. CONCLUSIONS: This case underscores the challenges in managing intracranial metastasis in pregnancy, necessitating a multidisciplinary approach for optimal management while minimizing harm. In this case, the ethical aspect of patient autonomy is evident as the patient and her family consented to the medical interventions, despite the risks involved. The principle of beneficence and non-maleficence is demonstrated through the medical team's diagnostic and medical interventions aiming to prevent unnecessary harm to the patient and fetus while still providing effective care for the patient. In terms of justice, the patients get fair access to healthcare resources and treatments, regardless of socioeconomic status. Unfortunately, the patient's condition worsened due to cancer progression. In conclusion, the case highlights the importance of respecting patient autonomy while striving to act in their best interests through beneficent medical intervention.

The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.

BACKGROUND: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC). METHODS: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR. RESULTS: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009). CONCLUSION: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision.

The Association of Immune Cell Infiltration with Metastasis Location in De Novo Metastatic Triple Negative Breast Cancer: A Multicenter Cross-Sectional Study in Indonesia.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns. METHODS: We conducted a multicenter cross-sectional study in 2022 to examine formalin-fixed paraffin-embedded (FFPE) and medical record data from 2015 to 2020 in de novo metastatic TNBC patients. The medical records provided crucial information about the sites of metastasis. Immunohistochemistry (IHC) analysis was carried out on primary breast tumor tissues to evaluate the expressions of cluster of differentiation (CD)4 T-cells, CD8 T-cells, CD163, FOXP3 Tregs, and programmed death-ligand 1 (PD-L1), along with immune cells ratios showing antitumor-to-protumor activity (CD4/FOXP3, CD8/FOXP3, CD4/CD163, CD8/CD163). Metastatic locations were grouped into bone-only, visceral, lung, liver, and brain metastasis.  Results: A total of 120 metastatic TNBC patients were documented for their metastatic location and IHC report. The clinical and histopathological characteristics showed that the majority of the patients were within the 40-65 years old group, and 34.2% had standard body mass index (BMI). Furthermore, the majority (89.22%) of the patients showed No Special Type (NST), (56.7%) had histopathology grade III, high Ki-67 ≥20% (85.8%), and positive PD-L1 expression (30.8%), with visceral metastasis indicating the highest proportion of 75.8%. Patients with a high CD8/FOXP3 and CD4/FOXP3 ratio were significantly prone to have bone-only metastasis compared to visceral metastasis (p= 0.028 and p=0.024, respectively).  Conclusion: The ratio of antitumor to protumor T-lymphocytes had a significant relevance in the metastatic location patterns in TNBC.

Correlation of Transferrin Saturation and Serum Ferritin with Bone Mass Density in Adult Transfusion Dependent Beta-Thalassemia Patients.

BACKGROUND: The use of regular blood transfusions and iron chelation therapy to treat thalassemia has improved survival and increased the incidence of osteoporosis. Moreover, iron toxicity is one of the contributing factors that reduce bone mass density in adult transfusion-dependent beta-thalassemia patients. Therefore, this study aims to determine the proportion of low bone mass density in adult thalassemia patients and transferrin saturation, as well as serum ferritin, which correlates to the skeletal condition. METHODS: This is a cross-sectional study conducted in Thalassemia and Hematology Medical Oncology Clinics of Cipto Mangunkusumo Hospital in March 2016. The anthropometric data and hemoglobin levels were obtained before transfusion. Subsequently, the average ferritin levels, bone mineral density, and radiographic results were obtained. RESULTS: The percentage of adult thalassemia major and intermedia patients with low bone mass density was 68%. Also, there was a weak inverse correlation between bone mass density and transferrin saturation (r = -0.329, p = 0.01), while no correlation was shown between bone mass density and ferritin (r = -0.088, p = 0.504). The transferrin saturation cutoff point value used to distinguish the incidence of low and normal bone density in patients with transfusion-dependent beta-thalassemia was 89.5%. In addition, there was weak correlation between Singh index and bone mass density (r = 0.273, p = 0.038). CONCLUSION: Among the transfusion-dependent beta-thalassemia patients, 68% had low bone mass density, which inversely correlated to transferrin saturation. Furthermore, the cutoff value of transferrin saturation to differentiate the incidence of low and normal bone density in thalassemia major compared to thalassemia intermedia was 89.5%. Singh Index correlates weakly with bone mass density and might be used to detect low bone mass density in remote healthcare facilities.

Anaphylaxis: lesson learned from five cases.

Anaphylaxis is a severe hypersensitivity reaction. Its clinical manifestations vary, affecting several organs at once. Skin symptom is the most frequent manifestation; however, diagnosis of anaphylaxis will only be established when involving one or both vital organs, which are cardiovascular and respiratory system. Other symptom, such as that involving central nervous system or gastrointestinal tract, may accompany. We present five cases of anaphylaxis which vary in onset of symptoms, allergen, degree of severity, therapeutic response and clinical manifestation. Anaphylactic reaction to drugs in these cases is mainly manifested as anaphylactic shock and reaction to food allergen causing obstruction of respiratory tract. Four anaphylactic events occurred at home and only one occurred in a hospital, thus education on anaphylaxis to general community is very important, especially for the patients and their families. Prompt medical assistance in patients with anaphylactic symptoms determines their therapeutic response. Skin test prior to administration of cephalosporin does not give negative predictive value toward anaphylactic event.