INTRODUCTION: Ovarian cancer is one of the leading causes of mortality in women. In 2020, 5,395 (6.2%) of diagnosed malignancies in females were ovarian in origin. It also ranked second among gynecologic malignancies after cervical cancer. The prevalence in Asian /Pacific women is 9.2 per 100,000 population. Increased mortality and poor prognosis in ovarian cancer are caused by asymptomatic growth and delayed or absent symptoms for which about 70% of women have an advanced stage (III/IV) by the time of diagnosis. The most associated gene mutations are Breast Cancer gene 1 (BRCA1) which is identified in chromosome 17q21 and Breast Cancer gene 2 (BRCA2) identified in chromosome 13. Both proteins function in the double-strand DNA break repair pathway especially in the large framework repair molecules. Olaparib is a first-line drug used in the management of ovarian cancer. It targets affected cells by inhibition of poly (ADP-ribose) polymerase (PARP) activity which induces synthetic lethality in mutated BRCA1/2 cancers by selectively targeting tumor cells that fail to repair DNA double-strand breaks (DSBs). OBJECTIVE: The study aims to determine the prevalence of pathogenic somatic mutations in BRCA1 and BRCA2 among patients diagnosed of having ovarian cancer, to characterize the identified variants into benign/ no pathogenic variant identified, variant of uncertain significance (VUS), and pathogenic, and to determine the relationship of specific mutations detected with histomorphologic findings and clinical attributes. METHODOLOGY: Ovarian cancer tissues available at the St. Luke’s Medical Center Human Cancer Biobank and formalin-fixed paraffin-embedded (FFPE) tissue blocks diagnosed as ovarian cancer from the year 2016 to 2020 were included. Determination of the prevalence of somatic BRCA1 and BRCA2 mutations using Next Generation Sequencing (NGS). RESULTS: A total of 60 samples were processed, and three samples were excluded from the analysis due to an inadequate number of cells. In the remaining 57 samples diagnosed ovarian tumors, pathogenic BRCA1/2 variants were identified in 10 (17.5%) samples. Among the BRCA1/2 positive samples, 3 (5.3%) BRCA1 and 7 (12.3%) BRCA2 somatic mutations were identified. CONCLUSION Identification of specific BRCA1/2 mutations in FFPE samples with NGS plays a big role in the management of ovarian cancer, particularly with the use of targeted therapies such as Olaparib. The use of this drug could provide a longer disease-free survival for these patients. Furthermore, we recommend that women diagnosed with ovarian cancer should be subjected to genetic testing regardless of the histologic subtypes or clinical features. Lastly, genetic testing should be done along with proper genetic counseling, especially for patients who are susceptible to these mutations.
ovarian cancer

RUNX1::RUNX1T1 is a core-binding factor driving fusion gene which arises from t(8;21)(q22;q22). It is one of the most common chromosomal rearrangements in both pediatric and adult Acute Myeloid Leukemia (AML) with a reported incidence o 15% in children and young adults. There are few case reports documenting RUNX1::RUNX1T1 translocation in pediatric AML. Although this is generally associated with a favorable prognosis, we report two (2) cases of de novo pediatric AML in the Philippines harboring a RUNX1::RUNX1T1 translocation, one eventually relapsed while the other attained remission but succumbed to sepsis.
Next Generation Sequencing ; RUNX1::RUNX1T1 fusion

Introduction: With advancements in the understanding of lung cancer biology, targeted therapy has become the rule rather than the exception. Patients with ALK rearrangements are amenable to therapy with Alectinib and other ALK inhibitors, which has been associated with better patient outcomes. While ALK rearrangement should be routinely tested in non-squamous non-small cell lung cancer (NSCLC), the cost and availability of this test is a prohibitive factor, particularly in the Philippine setting. Objectives: This study aimed (1) to determine the prevalence of ALK-rearranged NSCLC among adult Filipino lung cancer patients in St. Luke’s Medical Center (SLMC) from 2016 to 2018 and (2) to determine the clinico-pathologic features of adult Filipinos with ALK-rearranged NSCLC. Methodology: This is a retrospective cross-sectional descriptive study wherein the prevalence of ALK-rearranged NSCLC, detected using fluorescence in-situ hybridization (FISH) or immunohistochemistry (IHC), was determined. Clinical data of patients for whom ALK testing was performed were collected. Hematoxylin and Eosin (H&E) slides were retrieved and reviewed for the presence of certain morphologic features. Patients whose H&E slides cannot be retrieved were excluded from the study. Results: ALK rearrangement was seen in 7.8% (8/103) of tumors submitted for ALK testing. Patients with ALK-rearranged tumors were generally young, light smokers, and presented with advanced clinical stage. Clear cell features and solid pattern were noted in one case and three cases, respectively. However, due to small sample size, further statistical analysis could not be performed to analyze the association of these features with the presence of ALK rearrangement. Conclusion Despite a small sample size, the prevalence and clinical profile of ALK-rearranged NSCLC in our institution are congruent with those previously described in Western populations. The association of clinical profile and morphologic features with the presence of ALK rearrangement can be further explored in future studies.
Lung Neoplasms ; Anaplastic Lymphoma Kinase

Background: Gastrointestinal stromal tumors (GIST) is defined as specific, typically kit (CD117)-positive and CKIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation-driven mesenchymal tumors that can occur anywhere in the GI tract. GIST diagnosis relies heavily on immunohistomorphology. However, with the advent of molecular testing, the classification, diagnosis and targeted-therapy for gastrointestinal mesenchymal tumors have been greatly improved. In the Philippines, molecular testing is not yet readily available as in other countries. The local molecular profile of gastrointestinal stromal tumors is a point of investigation as treatment may be more tailored to the patients’ needs. Objective: This study aims to determine the prevalence of CKIT and PDGFRA mutations among formalin-fixed and paraffin embedded gastrointestinal stromal tumors and other gastrointestinal mesenchymal tumors in St. Luke’s Medical Center – Quezon City. Methods: A retrospective cross-sectional study of formalin fixed and paraffin embedded tumor samples diagnosed as Gastrointestinal Stromal Tumor from January 1, 2009 to December 31, 2017 will be analyzed for KIT and PDGFRA mutations. Result: The epidemiology of GIST remains constant in that mean age group is the 5th to 6th decade, with equal gender distribution, and stomach followed by small bowel are the most common sites. Mutational analysis of the GISTs showed predominantly KIT Exon 11 (47.83%) followed by CKIT Exon 9 (13.04%) and PDGFRA Exon 18 (10.87%). For KIT Exon 11, deletion is the most common mutations followed by point mutations. No mutation is detected in 47.83% of GISTs. Conclusion Mutational analysis for CKIT-PDGFRA is warranted among GIST patients, as it may significantly influence treatment protocol in our patients.
Gastrointestinal Stromal Tumors

Objective: The advent of immunotherapy has significantly changed the treatment and management of patients with advanced non-small cell lung cancer (NSCLC). Prior to initiation of immunotherapy, evaluation of programmed death ligand 1 (PD-L1) expression is required. One factor that affects PD-L1 expression in NSCLC is the presence of oncogenic driver mutations; however, little data on its association is available, especially in the Philippine setting. The study aims to determine the prevalence of PD-L1 expression and its association with driver mutations among patients with non-small cell lung cancer in a private tertiary care hospital in the Philippines. Methodology: The study was undertaken for a period of two years from July 2017-July 2019 at St. Luke’s Medical Center and included 446 NSCLC samples. PD-L1 was evaluated by immunohistochemistry using 22C3 anti-PD-L1 antibody clone, EnVision FLEX visualization system on Autostainer Link 48. Patient demographics and data on driver mutation testing were recorded. Statistical analysis was performed using logistic regression. Results: PD-L1 expression was observed in 273 (61.20%) of 446 cases, 119 (61.20%) of which demonstrated high PD-L1 expression while 154 (34.50%) had low PD-L1 expression. There was no significant association between PD-L1 expression and EGFR mutation, ALK mutation, age, and gender. For histologic type, high PD-L1 expression was significantly associated with adenocarcinoma and non- small cell carcinoma, NOS. Conclusion The overall prevalence of PD-L1 expression in non-small cell lung carcinoma is 61.20% based on the cases included. Although we did not find an association between PD-L1 expression and EGFR and ALK mutation, our study observed that ALK-mutated NSCLCs have 4.7 odds of having high PD-L1 expression, however, a higher sample size is warranted to truly determine significant association. The outcome of this study may provide help in the stratification of patients and predict those who will benefit from immunotherapy.
Carcinoma, Non-Small-Cell Lung ; B7-H1 Antigen

SARS-CoV-2 has infected more than 643 million individuals worldwide and accounts for close to 64,950 deaths in the Philippines. Due to COVID-19’s clinical overlap with other diseases and non-specific radiologic findings, its diagnosis rests primarily on laboratory methods, including reverse transcription polymerase chain reaction (RT-PCR) and multiplexed molecular platforms for rapid syndromic testing. Compared to RT-PCR which has a turnaround time of 24 to 72 hours, multiplexed molecular platforms can provide alternative diagnoses to COVID-19 in an average of one hour, providing meaningful data that can impact clinical and resource management when handling acute surge of patients with respiratory symptoms.
COVID-19 ; SARS-CoV-2

INTRODUCTION: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore. METHODS: Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by ¹³C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI. RESULTS: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674). CONCLUSION First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.
Humans ; Helicobacter pylori ; Clarithromycin/therapeutic use* ; Helicobacter Infections/drug therapy* ; Metronidazole/therapeutic use* ; Bismuth/therapeutic use* ; Singapore ; Drug Therapy, Combination ; Amoxicillin/therapeutic use* ; Proton Pump Inhibitors/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Treatment Outcome ; Clinical Audit

The management of Helicobacter pylori infection in Singapore remains a clinical challenge. Similar to other regions, there has been an increase in antibiotic resistance rates through the years. Nonetheless, over the past two decades, clarithromycin-based triple therapy has continued to be used as the first line treatment option, with an eradication rate exceeding 90%, although the accepted treatment duration must now be lengthened from 1 to 2 weeks to maintain efficacy. Concomitant and sequential therapies did not demonstrate superiority over standard triple therapy. Current empiric second line treatment utilizes either bismuth-based quadruple therapy or levofloxacin-based triple therapy, but outcomes remain less than ideal. Identifying options to further improve treatment success rates is challenging. Strategies being considered include the use of potent acid suppressants, such as vonoprazan, and H. pylori culture and antibiotic susceptibility testing-guided therapy.

INTRODUCTION: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. METHODS: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. RESULTS: Twelve recommendation statements were created and summarised. CONCLUSION Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore.
Adult ; Esophageal pH Monitoring ; Esophagus ; Humans ; Hydrogen-Ion Concentration ; Manometry ; Singapore

Introduction: The current management of advanced non-small cell lung cancer (NSCLC) includes the characterization of Programmed Death Ligand-1 (PD-L1) expression for potential immune checkpoint inhibitor treatment. There is currently no available data regarding the patterns of PD-L1 expression in NSCLC, as well as their association with clinicopathologic profile in Filipino patients. Methodology: Clinicopathologic characteristics of 187 consecutive NSCLC clinical samples with PD-L1 testing using the clone 22C3 pharmaDx kit were collected. The presence of stromal tumor-infiltrating lymphocytes (TILs) were assessed in hematoxylin and eosin-stained slides. PD-L1 expression on tumor cells (TC) and stromal TILs were evaluated. Results: Of the 187 cases, there were 112 males and 75 females. The mean age at diagnosis was 66.4 years old (32-92 years old). It is composed of 131 cases of Adenocarcinoma, 15 Squamous cell carcinoma, 4 Adenosquamous carcinoma, 32 Non-small cell carcinoma, not otherwise specified, 3 poorly differentiated malignancy, 1 Large cell carcinoma, and 1 Mucinous carcinoma. Specimen types included 17 pleural fluid cell blocks, 60 tumor cell block samples, and 110 tissue biopsies. Tumor cell PD-L1 expression was identified in 59.1% of the 110 tissue biopsies. PD-L1 TPS for histologic specimens are as follows: TPS >50%, TPS 1-49%, and TPS <1% were observed in 23.6%, 35.5%, and 40.9% in our lung cancer cohort, respectively. Of the 77 cytology specimens, 50.6% presented with TC PD-L1 expression. TPS for this subgroup include: 49.4% with no PD-L1 expression, 35.1% with low PD-L1 expression, and 15.6% showing high PD-L1 expression. PD-L1 expression on TC did not correlate with age, sex, or histology for both specimen type subgroups. Stromal tumor-infiltrating lymphocytes were noted in 74.5% of tissue biopsies. Tumor cell block samples did not demonstrate stromal TILs. For tissue biopsies, female gender and TPS 1-49% were more likely to have <50% PD-L1 expression on TILs. Conclusion Overall TC PD-L1 expression was observed in more than half (55.6%) of NSCLC patients in our cohort. The prognostic value of PD-L1 and clinical response to immune checkpoint inhibitors in the Filipino population needs to be further investigated.
Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Philippines