RUNX1::RUNX1T1 Fusion in Pediatric Acute Myeloid Leukemia: A description of two cases

@#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.

Prevalence of Somatic BRCA1 and BRCA2 mutations in ovarian cancer among Filipinos using next generation sequencing

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.

Guidance on performance and reporting of high-resolution oesophageal manometry and ambulatory pH monitoring in Singapore

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.

Helicobacter pylori Treatment Strategies in Singapore

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.

The diagnosis and management of H. pylori infection in Singapore

Helicobacter pylori (H. pylori) is an infection that has a role in causing dyspepsia and complications such as peptic ulcer disease and gastric malignancies. In the primary care setting, one can adopt a stepwise approach with the 'test-and-treat' strategy to manage H. pylori-associated dyspepsia in young patients without alarm symptoms. Empiric first-line therapies should be for a two-week duration; options include clarithromycin-containing triple therapy alone or with the addition of bismuth, concomitant therapy and bismuth quadruple therapy. Post-treatment carbon urea breath test must be performed at least four weeks after the end of treatment to confirm the cure. Options for empiric second-line treatment include bismuth quadruple therapy and levofloxacin-containing triple therapy. Patients with persistent or alarm symptoms should be referred for further evaluation. Patients with persistent infection should be referred for gastroscopy so that gastric biopsies can be obtained for H. pylori culture and antibiotic susceptibility testing.

Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.

Current status of functional gastrointestinal evaluation in clinical practice

Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient's care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients' persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools.

Ovarian carcinoma presenting with isolated contralateral inguinal lymph node metastasis: a case report

<p><b>INTRODUCTION</b>Ovarian carcinoma usually presents at an advanced stage with diffuse intraabdominal manifestations. We report a patient who presented with a right groin swelling.</p><p><b>CLINICAL PICTURE</b>The only clinical abnormality was an enlarged right inguinal lymph node (3 x 2 cm), for which excision biopsy revealed metastatic adenocarcinoma. A computed tomography (CT) scan showed an enlarged left ovarian lesion (9.0 x 6.4 cm).</p><p><b>TREATMENT AND OUTCOME</b>Laparotomy with total hysterectomy, bilateral salpingo-oophrectomy and partial omentectomy were performed. Histology confirmed left ovarian adenocarcinoma, consistent with the earlier histology of the right inguinal lymph node. There were no other sites of involvement. Postoperatively, the patient received adjuvant chemotherapy for treatment of FIGO Stage IIIc ovarian carcinoma and is clinically disease free 13 months after surgery.</p><p><b>CONCLUSIONS</b>Ovarian cancer presenting with inguinal lymph node metastases is uncommon. Ovarian cancer which manifests solely as a contralateral inguinal lymph node metastasis has not been previously reported. This case illustrates a rare presentation of ovarian carcinoma, and underscores the need to consider ovarian carcinoma in the differential diagnosis of women with inguinal lymphadenopathy.</p>