Malaysian Journal of Pathology最新文献

Hirschsprung's Disease (HD) is a congenital disorder causing severe constipation in infants and children. Suction rectal biopsy (SRB) is the preferred technique for obtaining tissue samples for histopathological evaluation. In low-resource settings like Malaysia, cost-effective diagnostic approaches are necessary, making single sample SRB valuable. This study evaluates the diagnostic accuracy and sufficiency of a single macroscopically adequate sample in suction rectal biopsies for the histopathological confirmation of HD. We conducted a retrospective study of children who underwent suction rectal biopsies for the diagnosis of HD at Hospital Raja Perempuan Zainab II (HRPZII), Kota Bharu, Kelantan. A total of 68 patients were included in the study. The inadequacy rate for bedside SRB was 14%, comparable to current literature. Our study found no statistically significant association between sample inadequacy and gestational age, gender, birth weight, or weight at biopsy. Complication rates were 0%, consistent with literature reports. Calretinin staining, an additional technique, was performed in 23 biopsy episodes, with a 4.3% inadequacy rate, compared to 20% in specimens not subjected to calretinin staining. The cost of SRB almost doubled with each additional sample taken, significant in low-resource environments. In conclusion, single sample SRBs can be adequately diagnostic and cost-effective in low-resource settings, providing valuable insights for healthcare facilities in Malaysia and other developing countries. The use of adjunctive techniques such as calretinin staining may improve diagnostic accuracy while maintaining cost-effectiveness. Further prospective studies with larger sample sizes are needed to validate these findings.

During the last few decades, the treatment options available for patients with metastatic colorectal cancer (mCRC) have undergone continuous improvements, transitioning from conventional chemotherapy to targeted therapy. These therapeutic innovations have led to significant improvements in patient clinical outcomes. However, there remains a need to improve the outcome for many CRC patients. Chemotherapy remains a cornerstone of CRC treatment, but the wide variability in tumour response and adverse reactions to chemotherapy poses a challenge to cancer treatment management. As a result, there is an unmet need to identify predictive biomarkers of chemotherapeutic response to guide treatment decisions. In this review, we summarise the conventional biomarkers used to predict chemotherapy responses in CRC and provide an overview of emerging predictive biomarkers based on the current understanding of the molecular biology of treatment response. Finally, we explore the challenges and future prospects of biomarker discovery to improve the prediction of patient response and ensure optimal treatment management for patients with metastatic CRC.

No abstract available.

Thyroid malignancy status is usually confirmed through histopathological examination (HPE) following thyroidectomy. In Malaysia, the application of molecular markers in pre-operative diagnosis of thyroid cancer remains unexplored. In this study, BRAF and NRAS gene mutation panel was assessed, and the results were compared with retrospective HPE findings. Malaysian patients with benign goitre (BTG: n=33) and papillary thyroid cancer (PTC: n=25; PTCa: n=20, PTCb: n=5) were recruited at Universiti Malaya Medical Centre from September 2019 to December 2022. PCR-direct DNA sequencing of BRAF^V600, NRAS^G12, NRAS^G13, and NRAS^Q61 was conducted on DNA extracted from the patients' thyroid tissue specimens following thyroidectomy and HPE. BRAF^V600E and NRAS^Q61R mutations showed absolute PTC-specificity with PTC-sensitivity of 32% and 28%, respectively. NRAS^Q61H demonstrated lower PTC-specificity (94%) but higher PTC-sensitivity (72%) compared to the BRAF^V600E and NRAS^Q61R mutations. Although the NRAS^G12 and NRAS^G13 variants were absent in this study, a novel NRAS^V14D mutation was detected in a PTCa patient. Unlike PTCb, coexistence of BRAF^V600E and NRAS^Q61 variants was commonly observed among the PTCa patients. Notably, all PTCb patients had NRAS^Q61H mutation with one patient carried both the NRAS^Q61H and BRAF^V600E mutations. Association analysis revealed potential link between gender, BRAF^V600E mutation and lymph node metastasis. In conclusion, mutation panel comprising BRAF^V600E, NRAS^Q61R, and NRAS^Q61H did not discriminate the two PTC subtypes but replicated the retrospective HPE findings in differentiating BTG from PTC. The application of this mutation panel in pre-operative diagnosis of thyroid nodules requires further validation in a larger sample size, preferably incorporating fineneedle aspirate biopsies.

Background: Candida tropicalis is a globally distributed yeast that has been popping up in the medical literature lately, albeit for unenviable reasons. C. tropicalis is associated with substantial morbidity, mortality as well as drug resistance. The aims of this study were to ascertain the antifungal susceptibility profile and the biofilm-producing capability of this notorious yeast in our centre.

Methods: C. tropicalis isolates from sterile specimens were collected over a 12-month period. Conclusive identification was achieved biochemically with the ID 32 C kit. Susceptibility to nine antifungal agents was carried out using the colourimetric broth microdilution kit Sensititre YeastOne YO10. Biofilm-producing capability was evaluated by quantifying biomass formation spectrophotometrically following staining with crystal violet.

Results: Twenty-four non-repetitive isolates of C. tropicalis were collected. The resistance rates to the triazole agents were 29.2% for fluconazole, 16.7% for itraconazole, 20.8% for voriconazole and 8.3% for posaconazole-the pan-azole resistance rate was identical to that of posaconazole. No resistance was recorded for amphotericin B, flucysosine or any of the echinocandins tested. A total of 16/24 (66.7%) isolates were categorized as high biomass producers and 8/24 (33.3%) were moderate biomass producers. None of our isolates were low biomass producers.

Conclusion: The C. tropicalis isolates from our centre were resistant only to triazole agents, with the highest resistance rate being recorded for fluconazole and the lowest for posaconazole. While this is not by itself alarming, the fact that our isolates were prolific biofilm producers means that even azole-susceptible isolates can be paradoxically refractory to antifungal therapy.

No abstract available.

Background: Information on incidence and risk factors associated with different types of neonatal pneumothorax were lacking globally.

Objectives: To determine incidences of pneumothorax developed spontaneously and during different modes of respiratory support, and risk factors associated with each type of pneumothorax.

Study design: Retrospective observational study of neonates in the Malaysian National Neonatal Registry.

Setting: 44 Malaysian neonatal intensive care units (NICUs).

Participants: All neonates born in 2015-2020 and admitted to NICUs.

Results: Pneumothorax developed in 3265 neonates: 37.5% occurred spontaneously, 62.5% during respiratory support. The incidence of all types of pneumothorax was 1.75 per 1000 livebirths, and of spontaneous pneumothorax was 0.58 per 1000 livebirths. Pneumothorax developed in 0.6% (450/70512) of neonates during continuous positive air way pressure therapy (nCPAPt), 1.8% (990/54994) of neonates during conventional mechanical ventilation (CMV), and 7.0% (599/8557) of neonates during high frequency ventilation (HFV). Term neonates had significantly higher pneumothorax rate than preterms (p<0.001). Multiple logistic regression analyses show that exposure to intermittent positive pressure ventilation and chest compression at birth were significant independent factors associated with increased risk of spontaneous pneumothorax and CMV, and persistent pulmonary hypertension was associated with increased risk of spontaneous pneumothorax and pneumothorax during CMV and HFV.

Conclusions: The most common type of pneumothorax was spontaneous in-onset. Neonates on HFV had the highest and those on nCPAPt the lowest rate of pneumothorax. Improving training of resuscitation techniques at birth and strategies of use of invasive modes of respiratory support may reduce incidences of all types of pneumothorax.

The onset of obstetric antiphospholipid syndrome (APS) occurs when antiphospholipid antibodies act upon the placenta. During pregnancy, APS exhibits traits such as vascular thrombosis, inflammation, and hindered trophoblast implantation. The involvement of microRNA expression has been proposed as a genetic factor contributing to the syndrome's development. MicroRNAs play a role in regulating gene expression in various cellular processes, including the formation of placental tissue. Therefore, additional research is needed to explore the control of placental miRNA in APS. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesised signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation while Retinoblastoma gene (RET), Dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) genes were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.

Background: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population.

Methods: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches.

Results: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L.

Conclusion: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

A rapid and accurate diagnosis of invasive fungal infections (IFIs) has been a great challenge particularly in cases requiring prompt antifungal treatment. In this study, four primer pairs were designed for a quadruplex PCR assay, which was developed for detection of four fungal species simultaneously. DNA extraction of cultured colonies and spiked blood samples were performed using conventional (phenol-chloroform) techniques and commercial DNA extraction kit. The optimum annealing temperature for this assay was 60°C. The assay was able to amplify all four genes and showed 100% specificity. No amplification of any genes was obtained against other species (n=14), which included two bacteria species. In conclusion, this quadruplex PCR assay is specific, rapid and reliable to detect A. fumigatus, A. terreus, C. albicans and C. glabrata simultaneously.