Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Sweat Gland Tumor Microenvironment.

Malignant sweat gland tumors are rare cutaneous neoplasms and associated with poor prognosis. The process of tumorigenesis originating from sweat glands is complex and dynamic. The tumor is surrounded by an extracellular matrix (ECM) and stromal cells, as well as physiological state from the tumor microenvironment (TME). Various types of evidence suggest a variety of vital components of TME that interact with each other, ranging from fibroblasts, immune and inflammatory cells, vascular and lymphatic networks, and ECM. This chapter provides a comprehensive overview of sweat gland tumor microenvironment based on current studies of TME and describes the function of each component of TME in cancer initiation, progression, and invasion.

Risk factors of distant metastasis after surgery among different breast cancer subtypes: a hospital-based study in Indonesia.

BACKGROUND: More than one third of breast cancer patients including those that are diagnosed in early stages will develop distant metastasis. Patterns of distant metastasis and the associated risks according to the molecular subtypes are not completely revealed particularly in populations of patients with delayed diagnosis and advanced stages. METHODS: Breast cancer patients (n = 1304) admitted to our institute (2014-2017) were evaluated to identify the metastatic patterns and the associated risks. Metastatic breast cancers at diagnosis were found in 245 patients (18.7%), and 1059 patients were then grouped into non-metastatic and metastatic groups after a median follow-up of 3.8 years. RESULTS: Infiltration of the tumor to the skin and chest wall prevailed as the most powerful predictor for distant metastasis (OR 2.115, 95% CI 1.544-2.898) particularly in the luminal A-like subtype (OR 2.685, 95% CI 1.649-4.371). Nodal involvement was also significantly associated with the risk of distant metastasis (OR 1.855, 95% CI 1.319-2.611), and the risk was higher in the Luminal A-like subtype (OR 2.572, 95% CI 1.547-4.278). Luminal A-like subtype had a significant higher risk of bone metastasis (OR 1.601, 95% CI 1.106-2.358). In respect to treatment, a combination of anthracyclines and taxanes-based chemotherapy was significantly associated with lower distant organ spread in comparison with anthracycline-based chemotherapy (OR 0.510, 95% CI 0.355-0.766) and the effect was stronger in Luminal A-like subtype (OR 0.417, 95% CI 0.226-0.769). Classification into Luminal and non-Luminal subtypes revealed significant higher risks of bone metastasis in the Luminal subtype (OR 1.793, 95% CI 1.209-2.660) and pulmonary metastasis in non-Luminal breast cancer (OR 1.445, 95% CI 1.003-2.083). CONCLUSION: In addition to guiding the treatment plan, a comprehensive analysis of clinicopathological variables including the molecular subtypes could assist in the determination of distant metastasis risks of breast cancer patients. Our study offers new perspectives concerning the risks of distant metastasis in breast cancer subtypes in order to plan intensive surveillance or escalation of treatment particularly in a setting where patients are predominantly diagnosed in late stages.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.

BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia. METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics. RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05). CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.

Transposable Elements in Human Cancer: Causes and Consequences of Deregulation.

Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

Deregulation of RB1 expression by loss of imprinting in human hepatocellular carcinoma.

The tumour suppressor gene RB1 is frequently silenced in many different types of human cancer, including hepatocellular carcinoma (HCC). However, mutations of the RB1 gene are relatively rare in HCC. A systematic screen for the identification of imprinted genes deregulated in human HCC revealed that RB1 shows imprint abnormalities in a high proportion of primary patient samples. Altogether, 40% of the HCC specimens (16/40) showed hyper- or hypomethylation at the CpG island in intron 2 of the RB1 gene. Re-analysis of publicly available genome-wide DNA methylation data confirmed these findings in two independent HCC cohorts. Loss of correct DNA methylation patterns at the RB1 locus leads to the aberrant expression of an alternative RB1-E2B transcript, as measured by quantitative real-time PCR. Demethylation at the intron 2 CpG island by DNMT1 knock-down or aza-deoxycytidine (DAC) treatment stimulated expression of the RB1-E2B transcript, accompanied by diminished RB1 main transcript expression. No aberrant DNA methylation was found at the RB1 locus in hepatocellular adenoma (HCA, n = 10), focal nodular hyperplasia (FNH, n = 5) and their corresponding adjacent liver tissue specimens. Deregulated RB1 expression due to hyper- or hypomethylation in intron 2 of the RB1 gene is found in tumours without loss of heterozygosity and is associated with a decrease in overall survival (p = 0.032) if caused by hypermethylation of CpG85. This unequivocally demonstrates that loss of imprinting represents an important additional mechanism for RB1 pathway inactivation in human HCC, complementing well-described molecular defects.

A new alternative to percutaneous nephrolithotomy: A case report.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is a common procedure for kidney stone removal, involving a small incision in the back and insertion of a nephroscope to extract the stones. Recent advancements include super-mini PCNL, employing smaller instruments for less invasive access to the kidney. However, conventional PCNL often requires tract dilation, which can lead to potential complications. CASE PRESENTATION: This case report presents the successful application of our surgical technique using the basic principles of PCNL with the aid of a pediatric trocar cystostomy and ultrasound guidance as a new alternative for super-mini PCNL, offering safer access with reduced bleeding risk and shorter recovery. The surgery was performed on a 55-year-old female with bilateral kidney stones, with the stone in the left kidney being larger than the one in the right kidney. The procedure was completed within 60 min without significant postoperative complications. DISCUSSION: Our new alternative for PCNL offers benefits such as reduced invasiveness, shorter recovery time, decreased risk of complications, and minimal changes in postoperative hemoglobin levels. This new alternative can be performed in developing country hospitals that do not have the expensive PCNL equipment. CONCLUSION: This new alternative of PCNL with pediatric trocar cystostomy proves to be effective and safe.

High P16INK4A Expression, Keratinizing Features, and Surgical Margin-Free Status are Associated with Improved Survival in Patients with Oral Squamous Cell Carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) continues to prevail as a highly prevalent cancer in Southeast Asia and causes a significant health burden. Stratification of patients with high risks of recurrence and mortality is important in the planning of treatment and surveillance. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues of OSCC were immuno-stained and analyzed for p16 expression. Risk factors and clinical parameters of OSCC patients were collected and compared to identify factors associated with recurrences and overall survival. RESULTS: After a median follow-up of 32 months, OSCC recurrences and mortality were observed in 82% and 78% of patients (N=60), respectively. Larger and more extensive tumors (T3 and T4) were significantly associated with both recurrences and cancer-associated mortality (OR = 3.967, 95% CI = 1.007-15.618 and OR = 5.885, 95% CI = 1.541-22.47, respectively). P16INK4A positive staining was found in 31% of tumors. Patients with p16INK4A positive staining were significantly associated with better recurrence-free and overall survivals (medians of recurrence-free survivals were 31.2 vs 19.0 months, P=0.038 and overall survivals were 39.0 vs 28.8 months,  P=0.048; respectively). Some other clinical characteristics including early stages, non-keratinizing tumors, negative cervical node, and free-surgical margin were significantly associated with better recurrence-free and overall survivals (log-rank tests, P<0.05). CONCLUSION: P16INK4A positive staining, early stages, negative cervical lymph node infiltration, and free-surgical margins are associated with better prognosis in OSCC patients. The study emphasizes the importance of early detection and the potential use of p16INK4A and other clinical variables to stratify OSCC patients with high risks of recurrence and worse overall survivals.

Long-Noncoding-RNA HOTAIR Upregulation is Associated with Poor Breast Cancer Outcome: A Systematic Review and Meta Analysis.

BACKGROUND: Breast cancer is the most frequent cancer among women worldwide with significant disproportionate mortality rates in developing countries. Although clinical management of breast cancer has been immensely improved, refinement in the prognostic and recurrent markers is still needed. Long non-coding RNAs (lncRNA) HOTAIR has recently been associated with poor outcome and is potentially used as a prognostic marker in breast cancer. METHODS: We comprehensively reviewed studies evaluating lncRNA HOTAIR in association with overall and disease-free survivals in breast cancers. Systematic searches were performed in Pubmed, ProQuest, ScienceDirect, Scopus, Google Scholar, Semantic Scholar, Springer, Nature, Sage Journals, and Wiley databases using combination keywords "long non-coding RNA," "lncRNA," "HOX transcript antisense RNA," "HOTAIR," "breast can-cer," "carcinoma mammae," "prognosis," and "survival." Risk of bias score was used to assess quality of studies, I2 test was conducted to assess heterogeneity. Meta-analysis was performed to compare HOTAIR expression with breast cancer survival rates using STATA v.17 software. RESULTS: Of the total 1,504 screened studies, seven studies were included in the meta-analysis involving 533 patients. High expression of HOTAIR was associated with poor survival rates (pooled HR: 1.69; 95%CI: 1.11-2.59; p=0.015), shorter overall survival (OS) (pooled HR: 1.33; 95%CI: 0.78-2.26; p=0.455), poor disease-free survival (DFS) (pooled HR: 2.40; 95%CI: 1.63-3.53; p<0.001), poor distant metastatic-free survival (MFS) (HR: 1.75; 95%CI: 1.13-2.71; p=0.012). In addition, overexpression of HOTAIR was associated with positive lymph node infiltration (pooled OR: 2.38; 95%CI: 0.53-10.69; p=0.26) and ductal type cancer (pooled OR: 3.27; 95%CI: 1.15-9.30; p=0.03). CONCLUSION: Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.

Utilizing Low-cost Vacuum-assisted Closure as Adjuvant Therapy in Soft Tissue Reconstruction for a Mangled Upper Extremity.

Soft tissue reconstruction using flaps in managing mangled injuries is occasionally insufficient due to large defects and low flap viability. Conversely, delaying the closure of the defect can elevate the risk of infection. Adjuvant therapy becomes essential in the management of mangled injuries. We aim to present the use of low-cost vacuum-assisted closure (VAC) as an adjuvant therapy for mangled injuries. We reported the case of a 20-year-old man who sustained a mangled injury to his left forearm in a traffic accident 4 hours before admission. The mangled extremity severity score was 9; however, the patient declined amputation. Although the initial reconstruction was done, the flap could only cover vital structures. VAC was utilized to address the uncovered portion of the defect, to promote optimal granulation and prevent infection. The reconstruction proceeded with a skin graft and wrist arthrodesis. At 1-year follow-up, viable tissue was obtained but contracture occurred at the metacarpophalangeal and proximal interphalangeal joints. We intend to perform functional reconstruction at a later stage. Although the benefits of VAC in wound management are well established, reports regarding its advantages in mangled injury management remain relatively scarce. The high cost of VAC is a limiting factor, particularly in developing countries. This prompts the need for an affordable VAC innovation with comparable efficiency to the commercial model. Reverse Aqua Pump VAC, our innovative low-cost VAC, shows satisfactory outcomes in managing patients with mangled injuries with mangled extremity severity score indicating amputation.

Concordant hypermethylation of intergenic microRNA genes in human hepatocellular carcinoma as new diagnostic and prognostic marker.

Epigenetic inactivation by aberrant DNA methylation has been reported for many microRNA genes in various human malignancies. However, relatively little is known about microRNA gene methylation in hepatocellular carcinoma (HCC). Therefore, a systematic screen for identification of aberrantly hypermethylated microRNA genes in HCC was initiated. The methylation status of 39 intergenic CpG island associated microRNA genes was analyzed in HCC cell lines (n = 7), immortalized hepatocytes (n = 2) and normal liver samples (n = 5). Subsequently, 13 differentially methylated microRNA genes were analyzed in primary human HCC samples (n = 40), benign liver tumors (n = 15) and the adjacent liver tissues employing pyrosequencing. Expression of microRNA genes was measured using quantitative real-time polymerase chain reaction (RT-PCR). In addition, DNA methylation and expression of microRNA genes were measured after DNMT1 knockdown or DNMT inhibition. Aberrant hypermethylation and concomitant reduction in expression of intergenic microRNA genes is a frequent event in human HCC: hsa-mir-9-2 (23%), hsa-mir-9-3 (50 %), hsa-mir-124-1 (20%), hsa-mir-124-2 (13%), hsa-mir-124-3 (43%), hsa-mir-129-2 (58%), hsa-mir-596 (28%) and hsa-mir-1247 (38%). Altogether, it affects 90% of the HCC specimens under study. MicroRNA gene methylation is not found in hepatocellular adenoma (n = 10) and focal nodular hyperplasia (n = 5). DNMT1 knockdown or DNMT inhibition reduced microRNA gene methylation and stimulated expression. In primary human HCC specimens hypermethylation and expression of microRNA genes showed an inverse correlation. Concordant hypermethylation of three or more microRNA genes is a highly specific marker for the detection of HCC and for poor prognosis.

MicroRNA Gene Signature for Predicting Mechanisms in Nasopharyngeal Carcinoma: A Case Study on the Potential Application of Circulating Biomarkers.

BACKGROUND AND AIM: Nasopharyngeal Carcinoma (NPC) is an upper respiratory tract cancer prevalent in Southeast Asia and related to chronic EBV infection. microRNAs (miRNAs) regulate gene expression implicated in NPC's carcinogenesis. However, this circulating RNA molecule's role and clinical utility remain unknown. Therefore, this study examined the circulation of miRNAs and their association with clinical data. METHODS: 160 plasma samples of NPC and 80 non-tumor samples were extracted to evaluate and validate the gene expressions. Quantification expression was performed using relative quantification of qPCR analysis level expression methods. The intrinsic cellular roles involving biological signaling in NPC's oncogenesis using Ingenuity Pathways Analysis (IPA) were also used. RESULTS: The results of the quantification significance profiling of NPC samples revealed decreased miR- 29c-3p (fold change 1.16; p<0.05) and increased 195-5p expression (fold change 1.157; p<0.05). Furthermore, the validation of hsa-miR-29c-3p expression on plasma NPC with known tumor vs. non-tumor and significant changes was also performed using a fold change of 4.45 (medians of 31.45 ± 1.868 and 24.96 ± 1.872, respectively; p<0.0005). miR-29c had a 2.14 fold change correlated with T primary status with a median of 31.99±1.319 and 31.35±2.412, respectively (p<0.05). Stage status with fold change 1.99 also had median levels of 31.98±1.105 and 31.21 ± 2.355, respectively (p-value <0.05). Furthermore, the node's status for the lower expression of miR-29c with fold change 1.17 had median levels of 32.78 ± 2.221 and 31.33 ± 1.689, respectively (p-value of 0.7). Bioinformatics analysis established the roles and functions of miR-29 in NPC progression, cell death and survival, cellular development, cellular function, and cell maintenance by inhibiting COL4A, PI3K, VEGFA, JUN, and CDK6. CONCLUSION: Overall, we conclude that decreased miR-29c expression is associated with poor clinical status and might inhibit NPC's five target genes.

Sociodemographic disparities associated with advanced stages and distant metastatic breast cancers at diagnosis in Indonesia: a cross-sectional study.

Background: The global health burden of breast cancer is increasing with 5-year survival rates being much shorter in low-income and middle-income countries. Sociodemographic and clinical disparities in early cancer detection affect long-term outcome. Methods: The authors compared social, demographic, and pathological characteristics associated with metastatic and late stages of breast cancer diagnosis using data collected from a special registry developed by Perhimpunan Bedah Onkologi Indonesia (PERABOI) in 2015. Results: Of 4959 patients recruited in this study, 995 women (20.1%) were diagnosed with metastatic breast cancer. Lower education status and living in rural areas were significantly associated with Stage IV at diagnosis [odds ratio (OR)=1.256, 95% CI=1.093-1.445, P=0.001; and OR=1.197, 95% CI=1.042-1.377, P=0.012; respectively). Main complaints other than lump (ulceration, breast pain, and discharge) and occupation as a housewife were also associated with the presentation of metastatic diseases (OR=2.598, 95% CI=2.538-3.448, P<0.001 and OR=1.264, 95% CI=1.056-1.567, P=0.030, respectively). Having lower education and living outside Java and Bali islands were associated with the diagnosis of late-stage breast cancers (OR=1.908, 95% CI=1.629-2.232, P<0.001 and OR=3.039, 95% CI=2.238-4.126, P<0.001; respectively). A higher proportion of breast cancer patients were relatively younger with bigger tumour size, positive axillary nodal involvement, and more frequent Human epidermal growth factor receptor 2 overexpression. Conclusion: The authors identified sociodemographic disparities in the metastatic and late-stage diagnosis of breast cancers among Indonesian women. The subsequent action is required to reduce disparities faced by women with lower social and educational levels for early diagnosis and better healthcare access.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Radiofrequency ablation for management of thyroid nodules in quarantine zone of COVID-19 pandemic setting in Indonesia.

Surgery using minimally invasive procedures has been continuously developing in the medical field including in the treatment and resection of thyroid tumors. In addition to open thyroid surgery, several types of procedures are well developed and adopted in our center including the endoscopic thyroid and radiofrequency ablation (RFA). The COVID-19 pandemic has substantially changed the healthcare system in Indonesia. Lack of oxygen and hospital wards, unaffordable screening tests, and limited health workers affect the perpetuation of non-emergency healthcare service including in the management of thyroid nodules. To preserve the resources needed during the pandemic, PFA for the thyroid procedure provides a better option in terms of hospital bed availability, healthcare cost, and patients' emotional distress. We safely conducted RFA procedures during the period of quarantine levels of 1-3 (low to high) by implementing COVID-19 protocols without any significant postoperative complications.

Extrathyroidal extension and cervical node infiltration are associated with recurrences and shorter recurrence-free survival in differentiated thyroid cancer: a cohort study.

BACKGROUND: Differentiated thyroid cancer has excellent overall survival. However, around 20% of patients experience recurrent diseases after a certain time of follow-up. Therefore, identification of risk factors for recurrence is necessary to adjust treatment and surveillance planning. METHODS: A retrospective study was conducted of 312 patients with differentiated thyroid cancer who received surgery with and without adjuvant treatment. Clinical and pathological risk factors were analyzed for recurrences. RESULTS: After median follow-up of 57 months, 109 of 312 patients (34.9%) developed recurrences. Extrathyroidal extension and positive cervical nodes were significantly associated with recurrences (OR = 2.449, 95%CI:1.260-4.760, P = 0.008 and OR = 3.511, 95%CI:1.860-6.626, P < 0.001; respectively). Lympho-vascular invasion (LVI) and tumor multifocality were also associated with increased risk of recurrence (OR = 2.577, 95%CI:1.380-4.812, P = 0.003 and OR = 1.602, 95%CI:1.001-2.495, P = 0.050; respectively). Using multivariable regression, only older age and tumor infiltration to the lymph nodes were significantly associated with recurrences (OR = 2.227, 95%CI:1.037-4.782, P = 0.040 and OR = 2.966, 95%CI:1.470-5.986, P = 0.002; respectively). In addition, T4, cervical lymph node infiltration, older age, and LVI were associated with shorter recurrence-free survival. CONCLUSION: Recurrence rates in our study population are relatively high. Extrathyroidal extension, positive neck lymph node, and older age were associated with recurrence risks of well differentiated thyroid cancers.

Cold abscess as a primary manifestation of thyroid tuberculosis.

Tuberculosis remains the highest cause of infection-related mortality in low- and middle-income countries. Extra-pulmonary tuberculosis is often misdiagnosed because of the nonspecific clinical presentations and gaps in the laboratory assessment. Delayed and misdiagnosis can cause increased risks of morbidity and potential community transmission. Primary thyroid tuberculosis is very rare presentation even in the endemic area. We presented a Case Illustrated of a patient with cold abscess as a primary presentation of thyroid tuberculosis. Difficulty in the diagnosis and treatment were described. Although very rare, atypical presentation of extra-pulmonary tuberculosis in the thyroid gland requires thorough anamnesis and in-depth examination. Clinicians should put high-index suspicion on high-risk patients from endemic areas with medical comorbidity including immunocompromised disease and poor nutritional status. Our report underlines the importance of thorough medical assessment for unusual presentation of thyroid tuberculosis.

Thyrotoxicosis occurrence in SARS-CoV-2 infection: A case report.

Introduction: Coronavirus Disease 2019 (COVID-19) is predominantly manifested as respiratory distress. There are growing reports of extrapulmonary clinical manifestations of COVID-19 in addition to the respiratory symptoms. COVID-19 has been associated with the thyroid function through Angiotensin-converting enzyme 2 (ACE2), the central mechanism through Thyroid Stimulating Hormone (TSH), and direct replication of the virus. Case presentation: A 26-year-old woman presented with complaints of palpitation and abdominal pain for three days. Because the symptoms were worsening, she was brought to the emergency room. Her temperature was 37.9 °C without any symptoms of cough, coryza, sneezing, nor headache. Physical examination revealed tremor, tachycardia with 162 beats per minute (bpm), excessive sweating, hyperreflexia of patellar reflex, and no prominent lump in the neck. Electrocardiography (ECG) showed supraventricular tachycardic rhythm (SVT) and 150 J cardioversions were performed. The ECG converted to sinus rhythm, regular, with 120 bpm. Thyroid function tests showed an elevated fT4 level (>7.77 ng/dL) and low TSH level (<0.005 µIU/mL). Chest X-ray showed slight cardiomegaly without prominent abnormality in the lungs that was confirmed with thoracic computerized tomography. The result of the rapid antigen test for COVID-19 was positive and confirmed with polymerase chain reaction testing. She was then treated in the intensive isolation room with remdesivir, anti-hyperthyroid, and supportive therapy. As her condition improved, she was shifted to a non-intensive isolation room and was discharged from the hospital at day 7. Discussion: COVID-19 could present as a thyroid crisis as the initial clinical manifestation. Clinicians should be aware that presentation of thyroid dysfunction in a patient without previous endocrine disease could be due to COVID-19 infection. Early recognition, anti-hyperthyroid therapy, and following isolation procedures for COVID-19 are required in the emergency condition.

Hemi-mandibulectomy without bony reconstruction: A case report of mandibular metastasis from a silent differentiated papillary thyroid cancer.

INTRODUCTION: Distant spread to the jaw is a rare metastatic manifestation from papillary thyroid cancer. Complete resection of tumor extension in the facial and oral regions requires consideration to compromise mastication functioning and facial aesthetics. Current advances in the microvascular surgery have facilitated excellent restoration of patient's functioning. Inadequate expertise, facility, longer surgery time and inpatient care, and healthcare insurance disbursement are common challenges in developing countries to perform microvascular surgery. CASE PRESENTATION: A 54-year female presented in an oncology clinic with a rapid progressive lump in the jaw without inflammatory signs. CT-scan revealed a 5.9x5.3 × 5cm lesion with osteo-destruction in the left mandible body. Biopsy was performed indicating a papillary adenocarcinoma invasion. Neck sonography showed hypoechoic nodule with regular border in the thyroid lobes. Fine-needle aspiration biopsy revealed benign follicular cells with Bethesda class II. Total thyroidectomy with frozen section and left hemi-mandibulectomy without bony reconstruction were then performed. Histopathological examination showed papillary thyroid cancer with follicular variant in the thyroid and mandible lesion. Thyroid ablation, TSH suppression, and chewing rehabilitation programs were accomplished by the patient. DISCUSSION: Partial mandibulectomy without bony reconstruction might be an option for selected patients with careful consideration from multidisciplinary team members in which extensive surgery with immediate bony reconstruction is not possible.

Risk Factors, Patterns, and Distribution of Bone Metastases and Skeletal-Related Events in High-Risk Breast Cancer Patients.

BACKGROUND: More than a quarter of breast cancer patients are at risk to develop recurrent metastases to the bone. OBJECTIVE: This study was designed to identify risk factors and predilections of bone metastasis and skeletal-related events (SRE) in a population of breast cancer survivors initially diagnosed in advanced stages and with high-risks of relapse. METHODS: Associated risk factors, distribution, and attainable treatment of bone metastasis and SRE were analyzed in a cohort of 1,329 breast cancer patients. The association with dependent variables was subsequently analyzed using multivariable logistic regression. Sociodemographic and adverse clinical characteristics were included as covariates of progression into bone metastasis and SREs. RESULTS: Of 1329 breast cancer patients, 246 patients (18.5%) were diagnosed as metastatic breast cancer in which 232 of them (94.3%) had bone metastases. Spines were the most common sites of bone metastases (25.6%). In multivariable analysis, advanced stage at diagnosis (OR=1.840, 95%CI:1.198-2.826, P=0.005), luminal subtype (OR=1.788, 95%CI:1.206-2.652, P=0.045), lobular histology (OR=1.795, 95%CI:1.012-3/184, P=0.046), positive axillary lymph node (OR=1.771, 95%CI:1.087-2.886, P=0.022), multiple metabolic comorbidities (OR=2.193, 95%CI:1.371-3.508, P=0.001), early menopause (OR=2.136, 95%CI:1.116-4.464, P=0.046) were significantly associated with risk of recurrent bone metastases. SREs occurred in 89 (68.5%) patients. Several risk factors for SREs were early menopausal age (OR=2.342, P=0.024), advanced stages (OR=1.404, P=0.039), lobular histology (OR=2.279, P=0.007), and having multiple metabolic comorbidities (OR=1.728, P=0.039). CONCLUSION: Bone metastases and SREs are relatively high in breast cancer patients diagnosed in advanced stages. Luminal subtypes, having multiple metabolic comorbidities, and lobular histology are associated with higher risks of recurrent bone metastases. Living in rural areas and advanced stage at diagnosis as a risk factors for bone metastases might represent a social gradient of care delivery.