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.

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.

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.

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.

Regulatory T Cells but Not Tumour-Infiltrating Lymphocytes Correlate with Tumour Invasion Depth in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common skin malignancy worldwide. Current evidence suggests tumour-infiltrating lymphocytes (TILs) may influence the clinical outcomes of patients with BCC. The present study aimed to profile the infiltrative characteristics of stromal TILs and regulatory T cells (Treg cells) in the tumour centre (TC), tumour periphery (TP), and normal adjacent tissue (NAT) of BCC. A total of 111 samples from 43 cutaneous BCC cases were examined for TIL (CD3+) and Treg cell (FOXP3+/CD3+) expression using immunohistochemical techniques. The correlations of Treg cells with TILs, invasion depth, and tumour morphological risk were analysed. We identified a high mean proportion of Treg cells within the tumour (TC = 46.9%, TP = 56.1%, NAT = 51.8%) despite a relatively low median of TILs (TC = 12.7%, TP = 10.3%, NAT = 3.6%), supporting the classification of BCC as a cold tumour. A significant positive correlation was observed between the proportion of Treg cells and sTILs (ρ = 0.325, p < 0.001), suggesting a predominant role of TILs in the infiltration of Treg cells. An inverse correlation discovered between Treg cells and tumour invasion depth (r = −0.36, p = 0.017) might indicate Treg cells' anti-tumour capacity in BCC.

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.

High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia.

OBJECTIVE: Thyroid cancer incidence has steadily increased in Indonesia. However, data on Kirsten rat sarcoma virus (KRAS) and EGFR mutations in thyroid cancer in Indonesia remain unavailable, except for BRAF-V600E, the most common BRAF gene mutation. This study aimed to analyze KRAS and EGFR mutation profiles in BRAF-V600E negative thyroid cancer samples. RESULTS: BRAF-V600E mutations were found in papillary thyroid carcinomas in 40.3% patients with mean age of 53 years old. In BRAF-V600E-negative samples, 41.3% had KRAS mutations with mean age of 55.5 years old. KRAS mutation was found in 52.6% of follicular carcinomas and 47.4% of papillary thyroid carcinomas. Additionally, 45.7% had EGFR mutations in patients with mean age of 50.5 years old. EGFR mutation was found in 71.4% of papillary thyroid carcinoma and 28.6% of follicular carcinoma. Nearly half of the BRAF-V600E negative thyroid carcinoma samples harbored either KRAS or EGFR mutations. This finding suggests that in BRAF-V600E negative thyroid carcinoma samples, testing for RAS and EGFR mutation may be warranted for further therapeutic consideration.

Circulation microRNA expression profiles in patients with complete responses to chemoradiotherapy in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is endemic cancer in Southeast Asia with a relatively poor prognosis. Chemoradiotherapy is a primary treatment that advantages certain patients, particularly in the early stages. New predictive and prognostic biomarkers are required to guide and select the best treatment. Aims: To evaluate the circulation expression profile of microRNAs (miRNAs) associated with responses to chemoradiotherapy in nasopharyngeal carcinoma. Methods: Peripheral blood from 17 patients was collected before and after chemotherapy and radiotherapy. Differential expression circulating miRNAs were analyzed using microRNA Cancer Panels and were compared among patients with complete responses. Differential expression analysis using GenEx 7 Multid, statistic represented by GraphPad Prism 9. Alterations mechanism signaling pathways and biological function using IPA (Ingenuity Pathways Analysis). Results: Using microRNAs Cancer Plate consisting of 116 miRNAs, we identified ten circulating miRNAs that were differentially expressed in NPC patients after chemoradiotherapy. Unsupervised clustering and confirmation using qRT-PCR showed that miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p were overexpressed and miRNA are miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p were significantly downregulated after chemoradiotherapy (p < 0.0001). In addition, ROC analysis through AUC (Area Under Curve) with 99% confidence interval (CI) p value < 0.0001. Gene enrichment analysis of microRNAs and the targeted proteins revealed that the main involved pathways for chemoradiotherapy in NPC were cell death and survival signaling pathways. Conclusion: qPCR profiling in circulating blood compared before and after chemoradiotherapy in nasopharyngeal carcinoma can identify pathways involved in treatment responses. miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p, miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p are differentially regulated after chemoradiotherapy in NPC.

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.

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.

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.

The prioritation and gap of preoperative COVID-19 vaccination in cancer surgery of the breast, head and neck, and skin: A cohort study of 367 patients in an Indonesian hospital.

BACKGROUND: Postoperative infection of Coronavirus Disease 2019 (COVID-19) has been associated with higher risks of mortality and pulmonary complication. Preoperative vaccination could significantly prevent postoperative-related mortality and morbidity particularly for cancer patients. METHODS: Cancer patients who were scheduled for elective major surgery were questioned for status and their willingness to receive COVID-19 vaccination and were prospectively monitored for the presence of postoperative COVID-19 infection and major complications. RESULTS: During the period of April-July 2021, 367 patients with median age of 49 years were scheduled for cancer surgery. Procedures for breast cancer were the most frequently performed (N = 166, 45.2%). Surgery procedures with potential aerosol generating procedures (AGPs) were performed in total of 104 patients (28.3%). Only 6 of 367 patients (1.6%) were fully vaccinated in the day of surgery and 351 patients (95.6%) were willing to receive COVID-19 vaccination. Fully vaccinated patients were significantly higher among those who were living in urban areas (OR = 22.897, 95%CI:4.022-130.357, P = 0.0001). Willingness to get the COVID-19 vaccination was significantly higher among female patients (OR = 4.661, 95%CI:1.685-12.896, P = 0.003). Postoperative COVID-19 infection was confirmed in 17 patients (4.6%) and major surgical complications were observed in 12 patients (3.3%). None of preoperatively vaccinated patients experienced postoperative COVID-19 infection or the related major complications. CONCLUSION: Although prioritizing COVID-19 vaccination in preoperative cancer patients has been recommended to prevent postoperative fatalities, only a small proportion of our patients have been vaccinated. Preoperatively vaccinated patients show advantages in the prevention of postoperative COVID-19 infection and major surgery complications. The slow rollout and disparity in the vaccination progress for patients requiring a major cancer surgery need to be specifically addressed.

Vigilance to misleading information is required to avoid delayed diagnosis: Case series of acral melanomas.

INTRODUCTION: Melanoma is considered a rare cancer among Asians with a wide range of mucocutaneous manifestations. Failure to recognize a lesion as melanoma at first presentation might delay surgery aimed at complete resection. Acral melanoma has been related with the highest rate of misdiagnosis (~30%) causing further delayed diagnosis. Reliability of patient' history taking in melanoma has not yet been systematically reported. PRESENTED CASES: Two patients visited our oncology clinic with pigmented lesions in their soles. A 66-year-old man disclosed it appeared since a year ago after accidently hitting a stone while farming. Physical examination showed a black-brown irregular 100 × 80 mm lesion covering the distal third of the right sole with ulceration in the central lesion. The second patient was a geriatric woman with a black-purple 25 × 27 mm lesion with slight protrusion and ulceration in the central, irregular border, and partial hyperkeratosis. She explained the lesion emerged two years ago after she accidently stepped on a nail. Both patients were then diagnosed with acral melanomas and were treated with wide-excision, closure with skin grafting, and inguinal dissection. DISCUSSION: Both patients reported history of traumas in lesions later confirmed as acral melanomas. Although history taking can provide up to 80% of the information for accurate diagnosis, in ambivalent cases, careful anamnesis, clinical examination, and biopsy are required to confirm diagnosis of acral melanoma. Early disease identification to establish definitive diagnosis of cancer is generally associated with better clinical outcomes. In suspected cases, vigilance toward misleading information in history taking is required.

Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma.

OBJECTIVE: Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue with clinicopathologic characteristics and survival in Indonesian primary nodular melanoma patients. RESULTS: Thirty-one tissue samples were obtained; two were excluded from survival analysis due to Breslow depth of less than 4 mm. The median survival of upregulated and normoregulated PD-L1-patients were 15.800 ± 2.345 and 28.945 ± 4.126 months, respectively. However, this difference was not significant statistically (p = 0.086). Upregulated and normoregulated NKG2A patients differed very little in median survival time (25.943 ± 7.415 vs 26.470 ± 3.854 months; p = 0.981). Expression of PD-L1 and NKG2A were strongly correlated (rs: 0.787, p < 0.001). No clinicopathologic associations with PD-L1 and NKG2A mRNA levels were observed. These results suggest that PD-L1 may have potential as a prognostic factor. Although an unlikely prognostic factor, NKG2A may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The mRNA levels of these two genes may help direct choice of immunotherapy and predict patient outcomes.

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.

Concurrent manifestations of Horner's syndrome and esophageal metastasis of breast cancer: case report of a young woman after a period of non-adherence to treatment: a case report.

BACKGROUND: Esophageal involvement and Horner's syndrome are rare manifestations of breast cancer distant metastases that can pose a significant challenge in diagnosis and treatment. In addition to the more aggressive behavior of breast cancer diagnosed in young women, non-adherence to treatment is associated with increased risk of distant metastasis. CASE PRESENTATION: A 36-year-old Javanese woman presented to our institution with dysphagia, hoarseness, and frequent hiccups. In the 6 weeks prior to the current admission, the patient also reported tingling in the neck and shoulder, anhidrosis in the left hemifacial region, and drooping of the upper left eyelid. She was previously managed as tuberculoid laryngitis. Plain X-rays showed burst fractures of the cervical vertebrae and slight pleural effusion. Laryngoscopy revealed bowing of the vocal cords and liquid residue in the vallecula that was reduced upon chin tuck. Esophageal metastasis was confirmed with endoscopy showing thickening of the wall and positive cytology swab with ductal malignant cells. The patient had a history of breast cancer with a period of loss to follow-up of 4 years. CONCLUSIONS: Physicians should consider potential distant metastasis of breast cancer to the esophagus and sympathetic nervous system of the neck particularly in a high-risk woman with presentation of dysphagia and manifestations of Horner's syndrome.

Pre-treatment neutrophil-lymphocyte and platelet-lymphocyte ratios as additional markers for breast cancer progression: A retrospective cohort study.

BACKGROUND: Breast cancer is the most prevalent cancer that causes significant morbidity and loss of productivity. Around a third of all breast cancer patients are potentially develop distant metastases albeit the current implementation of multidisciplinary treatment. A simple but effective marker to predict the risks of cancer progression is very important for clinicians to improve treatment and surveillance. METHODS: We recruited 1083 non-metastatic patients and analyzed the ratios of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) in relation to progression-free survivals (PFS) and risks of distant metastases. RESULTS: Baseline clinicopathological variables were not significantly different in the pretreatment NLR and PLRs. Using maximum points of sensitivity and specificity of the Receiver Operating Characteristic (ROC) curve, cut-off values were determined 2.8 for NLR and 170 for PLR. Higher NLR was associated with skin and chest wall cancer infiltration (T4, P = 0.0001). Elevated PLR was associated with more advanced stages at diagnosis (P = 0.03). High NLR values were significantly associated with risks of disease progression (OR 1.555, 95% CI: 1.206-2.005, P = 0.001). Patients with high NLR had shorter PFS (34.9 vs 53.5 months, Log-rank test = 0.001) and shorter time to develop recurrent distant metastatic disease (66.6 vs 104.6 months, Log-rank test = 0.027). CONCLUSION: High NLR is significantly associated with higher risk of disease progression and shorter time to develop metastases particularly among breast cancer patients diagnosed in the advanced stages.