Non-traumatic fat embolism (NTFE) is infrequently encountered in the clinical setting. The incidence of clinically detected fat embolism is less than 1%. It is diagnosed based on the evidence of fat emboli occluding the vessel lumen in a patient with no prior history of trauma. We report a case of NTFE in a lady who developed breathlessness and collapsed following home vaginal delivery. Post-mortem examination revealed extensive fat emboli in the pulmonary vessels. We elucidate the clinical challenges in diagnosing fat embolism (FE) in a patient without history of trauma.
Introduction: Cardiovascular disease (CVD) is the principal cause of admission and death in the Malaysian government hospitals. Method: The pattern of cardiac related mortality (CRM) cases in Hospital Serdang, Selangor was reviewed to determine the specific trends in ethnicity, age, gender and type of CRM. Data was drawn from the death registry records in Forensic Department of Hospital Serdang from January 2006 to December 2008. This preliminary project was carried out to assess the number of CRM cases and their characteristics to feed the decision to sensibly embark on another project related to atherosclerosis. Results: Out of 573 CRM cases, 84.5% were Malaysians out of which the majority were Malays (45.9%), fol- lowed by Chinese (30.2%), and Indians (22.1%). The majority were men (78.4%) with a mean age of death at 51.83 ± 14.10 (95% CI 50.52-53.14) years as compared to women (21.6%) with a mean age of death at 57.42 ± 16.92 (95% CI 54.41-60.43) years. Declining mortality trend was observed only in men. The 46-60 years old age group had the highest percentage of mortality and continually increase by year. Ischaemic heart disease (IHD) was the most common CRM type (69.1% in 2006, 66.2% in 2007, and 71.9% in 2008). Conclusion: We observed inconsistent trends of CRM in Hospital Serdang in terms of ethnicity, age, gender and type of CRM cases presented. Nevertheless, these findings do not necessarily represent the overall trends of CRM in Malaysia.
MicroRNAs (miRNAs) are small noncoding RNAs that involved in various normal and cancer-related cellular pro-cesses. Studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. miRNAs play a crucial role in HNSCC development, metastasis, prognosis and survival rate. Several studies have been conducted previously to investigate that use of miRNAs as the biomark-ers in disease diagnostic/prognostic and potential therapeutic targets management that may improve the outcomes of HNSCC. Our previous study revealed that upregulation of oncogenic miRNAs including hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221* were able to distinguish HNSCC from normal samples. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis.
Introduction: It is well known that cancer cells evade the immune system with the help of programmed cell death protein 1 (PD-L1) molecule to remain undetected, causing abnormal proliferation of T-cells. PD-L1 expression on the surface of neoplastic cells inhibits cytotoxic T-cell responses which lead to negative regulation of cytokines and proliferation of T-cells. The deleted in colorectal cancer (DCC) gene belongs to the immunoglobulin superfamily. It is a candidate of the tumour suppressor gene by regulating apoptosis. DCC assessment gives an insight into progno-sis in patients with advanced stages of CRC. Thymidylate synthase (TYMS) is a highly conserved enzyme involved in DNA synthesis. TYMS has been an important target for cancer chemotherapy because of its central, rate-limiting role in de novo synthesis of thymidylate. Expression of PD-L1, TYMS and DCC has been demonstrated to confer a prognostic value in CRC but none have been completely validated for patient care. This study aimed to determine the prognostic and predictive potential of PD-L1, TYMS, and DCC biomarkers in CRC. Methods: The expression of these biomarkers was evaluated immunohistochemically in 91 formalin-fixed paraffin-embedded (FFPE) archival tumour samples from patients that underwent surgical resection. Results: There was high expression of DCC in most cases; 84.6% (77/91). TYMS expression at a high level score was 46.2% (42/91) and at low level was 53.8% (49/91). Majority of cases had low PD-L1 expression in 93.4% (86/91) cases and high expression was detected in 6.6% (6/94) of cases. In addition, there was a significant association between TYMS expression with gender (P < 0.05) with distribution of TYMS expression detected at high level was 76.2% in male and 23.8% in female. The Kaplan-Meier survival plot showed mean overall survival in patients with PD-L1 with high expression to be 22 months, which pre-dicts better survival. TYMS low expression showed mean overall survival of 90 which also indicated better survival. DCC high expression showed mean overall survival of 90 which indicated better survival. The correlation between the biomarkers and overall survival were not statistically significant. Conclusion: The results from this study suggest that PD-L1, TYMS and DCC expression could be used as biomarkers to predict treatment outcome in CRC. PD-L1 overexpression predicts patients who could benefit from anti-PD-1 and anti-PD-L1 immunotherapy whilst TYMS low expression predicts patients who could benefit from 5-fluorouracil therapy. DCC high expression tumours predicts a better prognosis and overall survival compared to DCC-negative tumours in advanced CRC.
Introduction: Aberrant expression of E-cadherin has shown to have correlation with advanced disease of prostate cancer. In this study, we evaluated the potential of E-cadherin as a prostate cancer prognostic marker and determined its correlation with patient outcomes. Method: 46 prostate cancer specimens in the form of paraffin-embedded tissue blocks were retrieved from the Histopathology Unit, Department of Pathology, Hospital Kuala Lumpur. The expres- sion patterns of E-cadherin were determined by immunohistochemistry staining. The E-cadherin expression was evaluated and scored as positive (3+) and negative or loss of expression (2+ and 1+). The correlations of E-cadherin expression with patient outcomes which included biochemical failure, disease-free, metastasis and local recurrence were determined. Correlations of E-cadherin expression with the currently used traditional clinicopathological pa- rameters were also evaluated. Results: There were significant correlations between E-cadherin expression with bio- chemical failure (p=0.005) and local recurrence (p=0.003). However, there were no significant correlations between E-cadherin expression with disease-free (p=0.864) and tumour metastasis (p=0.430). Comparing the correlation of E-cadherin expression with the traditional clinicopathological parameters, there were significant correlations be- tween E-cadherin expression with pathological staging (p=0.001), Gleason score (p=0.004) and perineural invasion (p=0.001). However, there was no significant correlation between E-cadherin expression with positive tumour mar- gin (p=0.320). Conclusion: These results support the potential use of E-cadherin as a prognostic tool for prostate cancer as well as an additional marker along the currently available traditional clinicopathological parameters.
Superficial angiomyxoma (SA) is an angiomyxoid cutaneous tumour. It has predilection for the head and neck, torso, limbs and genital tract. Our case is a 27-year-old female, presented with painless right medial canthal mass for two years. It was associated with tearing when the lesion grew larger. We received a nodular brownish tissue measuring 25x20x15mm with homogenous brownish cut surface. Microscopically, the tumour was partially circumscribed, exhibiting bland stellate to spindle cells of moderate cellularity with pale eosinophilic cytoplasm, indistinct border, in a loose collagenous myxoid matrix with numerous blood vessels of different calibre. The lesional cells were present at the resected margin and were nonreactive towards CD34, SMA and S100. SA of the eyelid is sometimes mistaken clinically as dermoid cyst or lipoma. Reports have shown increased risks of local recurrence following incomplete excision. Close association with Carney’s complex is an important feature. Careful clinicopathologic correlation and proper investigations are needed for optimal patient care.
Introduction: This study aimed to investigate the effect of saffron extract and crocin on blood biomarkers associated with obesity using the rat model.
Methods: Obesity was induced by feeding a high-fat diet to 42 male Sprague-Dawley rats for 12 weeks, after which they were equally distributed into seven groups. Three groups served as controls namely, normal diet (ND), high-fat diet (HFD), and high-fat diet plus orlistat (HFD + ORL), while the remaining four treatment groups consisted of HFD added low or high dose (40 and 80 mg/kg/day) of either saffron extract or crocin in the food. At the end of 8 weeks, blood samples were collected by cardiac puncture for biochemical analysis.
Results: Obese rats treated with a high dose of saffron extract and crocin showed significantly lower plasma glucose levels (5.26 and 5.67 mmol/L respectively) than the HFD rats (6.92 mmol/L). Saffron extract and crocin at a high dose showed significantly lower levels of plasma insulin (3.97 and 3.88 ng/mL respctively) compared to HFD control (5.41 ng/mL). Adiponectin levels significantly increased in obese rats fed saffron extract and crocin at high doses (7.44 and 7.92 µg/mL respectively) compared to HFD control (5.34 µg/mL). Ghrelin level significantly increased from 419.10 to 284.10 pg/mL,while leptin level significantly decreased from 8.08 to 5.68 ng/mL for the high dose crocin groups compared to HFD control. No significant differences in plasma serotonin levels were found among the groups.
Conclusion: Saffron extract and crocin show potential in reducing blood biomarkers associated with obesity as well as anti-inflammatory and regulatory potential of adipocytokines in an animal model.
Inflammation plays an important role to the process of prostate carcinogenesis by increasing the rate of cell proliferation,
which contributes to an aggressive tumour phenotype. Cyclooxygenase-2 (COX-2) has been found overexpressed in
various types of cancer cells including prostate. The aim of this study was to investigate the COX-2 expressions in different
types of human prostate tissues. Paraffin-embedded prostate tissues from 263 samples were examined for the expression
of COX-2 marker by immunohistochemistry method. COX-2 was found highly expressed in prostate adenocarcinoma
(p=0.001) as compared to benign and normal tissues. The score of COX-2 expressions in most of normal prostate was
weak 49 (77.8%), while only 16 (16%) of BPH showed strong expression. 56 cases (56%) prostate cancer showed strong
COX-2 expression. Prostate cancer cases showed significant differences in staining patterns as tumour grade increased.
In addition, COX-2 expression was significantly correlated with Gleason score in cancerous tissues. This study suggests
that COX-2 overexpression is associated with prostate cancer and higher grade tumour.
Introduction: Colorectal cancer (CRC) arises from the cumulative effects of genetic and epigenetic alterations. Cur- rent treatment of metastatic CRC relies on combination of chemotherapy and targeted therapies such as anti-EGFR therapies. The success of targeted therapies relies on the detection of actionable targets and predictive biomarkers of resistance. The study aims to determine mutations in common actionable targets and predictive biomarkers of re- sistance to anti-EGFR therapies in Malaysian CRC patients. Methods: Mutations in 10 CRC tissues were determined by next-generation sequencing with a panel of 7 cancer-related genes covering all exons in KRAS, BRAF, PIK3CA, PTEN, TP53, NRAS, and EGFR genes. Immunohistochemistry was used to determine mismatch repair (MMR) status. Results: Of the ten samples, 5 and 4 samples harboured two and one mutation, respectively and one had no mu- tation. All were missense mutations and were in five genes, namely, KRAS, PIK3CA, TP53, BRAF, and EGFR. They were, G12D, G12V, G12A, G13D, and V14I in KRAS, E545K, K733R, and D1056N in PIK3CA, G199V, D259Y, and R282W in TP53, V600E in BRAF and G696R in EGFR. Deficient mismatch repair (dMMR) was detected in three samples, of which two had KRAS mutation. Conclusion: Mutations in KRAS codon 12 and 13, BRAF and PIK3CA which predict resistance to anti-EGFR therapies and three TP53 mutations were found. This is the first report of EGFR mutation in Malaysian CRC patients. It is predicted to be a pathogenic variant. dMMR, one of the biomarkers for treatment with immune checkpoint inhibitor was also detected.
Thirty-six adult male SD rats, weighing 200-250 g were used in this study. Dietary obesity was induced by feeding high-fat diet (HFD) for 12 weeks. One group of animal (n=6) served as normal control which received normal diet from the beginning to the end of the study. The other 30 male obese animals induced by HFD were randomly divided into five experimental groups: The group which received high-fat diet considered as a negative control and the other four groups were treated with saffron extract and crocin in low and high dosages of 40 and 80 mg/kg for 8 weeks. At the end of treatment period, kidney and pancreas were removed and stained with hematoxylin and eosin (H&E). There were significant histopathological changes, such as tubular degenerative, vascular congestion and interstitial inflammation in the kidney and extensive pancreatic adipose tissue infiltration in high-fat diet rats group when compared with normal control. The results showed less significant histopathological changes of the kidney and also moderate pancreatic adipose tissue infiltration in the groups treated with crocin. Interestingly saffron extract dose-independently displayed significant renal protective effect while a significant decrease in pancreatic adipose tissue infiltration was observed in obese rat treated with high dose of saffron extract (80 mg/kg). From these results, it can be concluded that consumption of saffron extract reduced the untoward effects of high-fat diet in kidney and pancreas of high-fat diet induced obese rats.
Renal cell carcinoma (RCC) is the most common renal malignancies. In advanced stage, it is highly resistant to systemic therapies. RCC is a highly vascular tumour and angiogenesis pathway has been postulated in its carcinogenesis. Novel drug targeting Vascular Endothelial Growth Factor (VEGF) and advanced surgical interventions have shown to increase the overall patients’ survival. In this study, we evaluated the VEGF expression of RCC using immunohistochemistry technique and its potential correlation with the tumour grades. Methods: 40 RCC cases that underwent nephrectomy were selected. The archived samples of formalin fixed, paraffin-embedded (FFPE) were retrieved. The tumour tissue blocks were carefully chosen, sectioned and stained with VEGF using immunohistochemistry technique. The intensity of VEGF expression was scored as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong). Results: Majority of the RCC cases were male, with male to female ratio of 2.1:1. Mean patient age was 56.2 years (age ranged between 16 to 74 years). Most of the cases were Malays (42.5 %). VEGF was expressed in 36 (90%) of RCC cases. Among the 36 cases that were immunopositive, 8 (16.7%) were grade 1, 20 (55.6%) grade 2 and 8 (16.7%) grade 3. There was no significant association between VEGF expressions score and grades of RCC (p=0.39). Conclusion: VEGF was expressed in majority of RCC cases although there was no significant association with tumour grades.
Introduction: Suspicious adnexal masses need to be investigated thoroughly as it may represent ovarian cancer, which is the fourth most common gynaecological cancer in Malaysia. Conventional cross sectional imaging may reveal non-specific findings, thus lead to unnecessary biopsies. 18F-Fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) has emerged as a useful tool, for characterization of indeterminate adnexal masses. Most studies have been conducted in Western population, and little information is available in Asian population in general and Malaysian population in particular. Methods: Prospective study of women with suspicious adnexal masses, referred to the Centre for Nuclear Diagnostic Imaging, Universiti Putra Malaysia to undergo pre-operative whole-body contrast-enhanced 18F-FDG PET/CT scans from January 2014 to January 2016. Subjects underwent Contrast-Enhanced Computed Tomography (CECT) scans followed by positron emission tomography (PET) scans using a hybrid scanner. Two radiologists analyzed the CECT and PET/CT images by consensus; blinded to the HPE results. Then the PET/CT findings were correlated with HPE results as the gold standard. Results: 11 whole-body PET/CT scans and 18 adnexal masses (12 HPE-proven malignant lesions and 6 benign lesions) were analyzed. The sensitivity, specificity, PPV, and NPV of CECT alone compared to PET/CT was 91.7%, 50.0%, 78.6%, and 75.0% vs. 91.7%, 100%, 100% and 85.7% respectively. Conclusions: Improved diagnostic accuracy for characterizing benign and malignant adnexal masses can be achieved using contrast-enhanced 18F-FDG PET/CT, making it a potential investigation of choice which can help in treatment planning.
Different murine species differ in their susceptibility to systemic infection with Candida albicans, giving rise to varied host immune responses, and this is compounded by variations in virulence of the different yeast strains used. Hence, this study was aimed at elucidating the pathogenesis of a clinical C. albicans isolate (HVS6360) in a murine intravenous challenge model by examining the different parameters which included the counts of red blood cells and associated components as well as the organ-specific expression profiles of cytokines and chemokines. Kidneys and brains of infected mice have higher fungal recovery rates as compared to other organs and there were extensive yeast infiltration with moderate to severe inflammation seen in kidney and brain tissues. Red blood cells (RBCs) and haemoglobin (Hb) counts were reduced throughout the infection period. Pattern recognition receptors (PRRs), chemokines and cytokine transcription profiles were varied among the different organs (kidney, spleen and brain) over 72 h post infections. Transcription of most of the PRRs, cytokines and chemokines were suppressed at 72 h post infection in spleen while continuous expression of PRRs, cytokines and chemokines genes were seen in brain and kidney. Reduction in red blood cells and haemoglobin counts might be associated with the action of extracellular haemolysin enzyme and haeme oxygenase of C. albicans in conjunction with iron scavenging for the fungal growth. Renal cells responsible for erythropoietin production may be injured by the infection and hence the combined effect of haemolysis plus lack of erythropoietin-induced RBC replenishment leads to aggravated reduction in RBC numbers. The varied local host immune profiles among target organs during systemic C. albicans infection could be of importance for future work in designing targeted immunotherapy through immunomodulatory approaches.
Local cytokine production is a significant indicator for disease pathogenesis or progression. Previous studies on cytokine production during systemic Candida albicans (C. albicans) infection were solely on kidney or single cell type interaction with C. albicans. Therefore, the present study aimed to assess the early cytokine expression of various target organs (kidney, spleen and brain) over a 72-h time course during systemic C. albicans infection. The local cytokine profiles of the target organs during systemic C. albicans infection were measured by cytometric bead array and ELISA analysis. The results demonstrated that interleukin-6 (IL-6) and IL-2 were statistically significant (P<0.05) in the spleen at 24 and 72 h post-infection, whereas in the kidney, IL-6 and tumor necrosis factor-α (TNF-α) were statistically significant (P<0.05) at 24 and 72 h post-infection and CXCL-1 and transforming growth factor-β (TGF-β) were statistically significant (P<0.05) at 72 h post-infection. In the brain, IL-6 and TNF-α were statistically significant (P<0.05) at 24 and 72 h post-infection, whereas TGF-β was statistically significant (P<0.05) at 72 h post-infection. These findings demonstrate that host immune responses were varied among target organs during systemic C. albicans infection. This could be important for designing targeted immunotherapy against this pathogen through immunomodulatory approaches in future exploratory research.