Displaying publications 1 - 20 of 38 in total

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  1. Anbarasen L, Lim J, Rajandram R, Mun KS, Sia SF
    PeerJ, 2019;7:e7058.
    PMID: 31275742 DOI: 10.7717/peerj.7058
    Background: Matrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients' tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease.

    Methodology: Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.

    Result: MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.

    Conclusion: Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers' potential applications as primary medical therapy targets for BAVM patients.

  2. Anthony R, Rajandram R, Yap NY, Mun KS, Samberkar PN, Kuppusamy S
    Malays J Pathol, 2023 Aug;45(2):261-269.
    PMID: 37658535
    BACKGROUND: Ubiquitously Transcribed Tetracopeptide Repeat on X Chromosome (UTX) and Jumonji Domain-Containing Protein 3 (JMJD3) are histone H3 lysine 27 (H3K27) demethylases that are found to play tumour suppressor or oncogenic roles in many cancers. However, their roles in urothelial carcinoma (UC) have not been well studied.

    OBJECTIVE: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.

    PATIENTS AND METHODS: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.

    RESULTS: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.

    CONCLUSIONS: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.

  3. Balasekaran N, Soelar SA, Anbarasen L, Cham CY, Rajandram R, Sia SF
    Med J Malaysia, 2021 Jan;76(1):17-23.
    PMID: 33510103
    BACKGROUND: Spontaneous subarachnoid haemorrhage (SAH) is a significant cause of stroke and associated with high morbidity and mortality. One substantial complication of SAH is cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). This study aimed to define the clinical profile in patients with SAH, CV and DCI secondary to spontaneous SAH (aneurysmal and pretruncal non-aneurysmal).

    MATERIALS AND METHODS: We analysed 122 consecutive patients with spontaneous SAH following intracranial aneurysmal and non-aneurysmal information (including patients' pattern characterisation and their possible risk factor association to pre-operative clinical decision and long-term clinical outcome) was documented and analysed.

    RESULTS: The main clinical presentations for spontaneous SAH following ruptured intracranial aneurysm and nonaneurysm were headache (77%) and nausea/vomiting (62.3%). The most common sites for SAH following ruptured intracranial aneurysm rupture were the anterior and posterior communicating arteries (57.5%). Hypertension was the most common cause for SAH at 64.8%. It was found 26.2% (n=32) out of the 122 patients developed CV and DCI. The mean day of vasospasm was 6.0 ± 2.8 (range: 1-14 days) Age, length of stay, nausea/vomiting and visual field defect were significantly associated (p<0.05) with vasospasm. Mortality rate was also higher in the CV group compared to the group without CV in both at discharge and at 6 months; 281 versus 278 per 1000 and 312 vs 300 per 1000, respectively.

    CONCLUSION: CV and DCI have a significant incidence among local patients with spontaneous SAH following an intracranial aneurysmal and non-aneurysmal rupture and it is associated with substantial morbidity. Prevention, effective monitoring, and early detection are keys to successful management. Regional investigation using a multicentre cohort to analyse mortality and survival rates may aid in improving national resource management of these patients.

  4. Bennett NC, Rajandram R, Ng KL, Gobe GC
    J Kidney Cancer VHL, 2014;1(2):17-25.
    PMID: 28326246 DOI: 10.15586/jkcvhl.2014.9
    Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.
  5. Chai CA, Yeoh WS, Rajandram R, Aung KP, Ong TA, Kuppusamy S, et al.
    Front Surg, 2021;8:659292.
    PMID: 34055868 DOI: 10.3389/fsurg.2021.659292
    Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center. Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT). Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36-89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding. Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.
  6. Chinapayan SM, Kuppusamy S, Yap NY, Perumal K, Gobe G, Rajandram R
    Diagnostics (Basel), 2022 Dec 06;12(12).
    PMID: 36553076 DOI: 10.3390/diagnostics12123069
    Renal cell carcinoma (RCC) is the most lethal genitourinary malignancy. Obesity is a risk factor for RCC development. The role of adipokines in the relationship between obesity and RCC requires confirmatory evidence in the form of a systematic review and meta-analysis, specifically for visfatin, omentin-1, nesfatin-1 and apelin. A search of databases up to July 2022 (PubMed, Web of Science and Scopus) for studies reporting the association of these selected adipokines with RCC was conducted. A total of 13 studies fulfilled the selection criteria. Only visfatin (p < 0.05) and nesfatin-1 (p < 0.05) had a significant association with RCC. Meanwhile, apelin and omentin-1 showed no association with RCC. The meta-analysis results of nesfatin-1 showed no association with early-stage (OR = 0.09, 95% CI = −0.12−0.29, p = 0.41), late-stage (OR = 0.36, 95% CI = 0.07−1.89, p = 0.23) and low-grade (OR = 1.75, 95% CI = 0.37−8.27, p = 0.48) RCC. However, nesfatin-1 showed an association with a high grade of the disease (OR = 0.29, 95% CI = 0.13−0.61, p = 0.001) and poorer overall survival (OS) (HR = 3.86, 95% CI = 2.18−6.85; p < 0.01). Apelin showed no association with the risk of RCC development (mean difference = 21.15, 95% CI = −23.69−65.99, p = 0.36) and OS (HR = 1.04, 95% Cl = 0.45−2.41; p = 0.92). Although the number of studies evaluated was limited, analysis from this systematic review and meta-analysis indicate that visfatin and nesfatin-1 were elevated. In summary, these adipokines may play a role in the development and progression of RCC and hence may have potential diagnostic and prognostic capabilities for RCC.
  7. Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
    PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048
    Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
  8. Golkhalkhali B, Rajandram R, Paliany AS, Ho GF, Wan Ishak WZ, Johari CS, et al.
    Asia Pac J Clin Oncol, 2018 Jun;14(3):179-191.
    PMID: 28857425 DOI: 10.1111/ajco.12758
    AIM: Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy.

    METHODS: A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein.

    RESULTS: The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004).

    CONCLUSION: The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy.

  9. Golkhalkhali B, Paliany AS, Chin KF, Rajandram R
    Nutr Cancer, 2018 01 11;70(2):184-191.
    PMID: 29324050 DOI: 10.1080/01635581.2018.1412470
    The prevalence of colorectal cancer (CRC) is on a steady rise over the years, with the World Health Organization (WHO) reporting CRC as the fourth leading cause of cancer-related death worldwide. While treatment modalities may differ in accordance to the staging and severity of the disease itself, chemotherapy is almost unavoidable in most cases. Though effective in its mode of action, chemotherapy is commonly associated with undesirable side effects that negatively affects the patient in terms of quality of life, and in some cases may actually interfere with their treatment regimens, thus escalating to poor prognosis. Gastrointestinal disturbances is a major side effect of chemotherapy and in CRC, gastrointestinal disturbances may be further aggravated and grave in nature mainly due to the affected site, being the gastrointestinal tract. The use of complementary therapies as adjuncts to alleviate the side effects of chemotherapy in CRC patients is gaining prominence with dietary supplements being the most commonly employed adjunct. Some of the frequently used dietary supplements for CRC patients are probiotics, omega-3 fatty acid and glutamine. The successful crosstalk between these dietary supplements with important metabolic pathways is crucial in the alleviation of chemotherapy side effects.
  10. Jayasimhan S, Yap NY, Roest Y, Rajandram R, Chin KF
    Clin Nutr, 2013 Dec;32(6):928-34.
    PMID: 23561636 DOI: 10.1016/j.clnu.2013.03.004
    Probiotics is an emerging therapeutic agent which may alleviate the symptoms of constipation. We evaluated the effectiveness of microbial cell preparation (Hexbio(®)) containing fructooligosaccharide, Bifidobacterium and Lactobacillus in improving stool frequency and symptoms of chronic constipation.
  11. Koong JK, Rajandram R, Sidambram N, Narayanan V
    Surgeon, 2021 May 08.
    PMID: 33975807 DOI: 10.1016/j.surge.2021.04.002
    BACKGROUND: Consent is an important component of surgical care. Poorly attempted consent bears significant ethical and legal implications. We assessed the effectiveness of handouts in improving postoperative consent understanding and recall compared to standard verbal consent during laparoscopic cholecystectomy as a tool that may improve information retention and leads to better treatment satisfaction.

    METHODS: This is a prospective block randomized, non-blinded study conducted at a single tertiary hospital. Patients undergoing elective laparoscopic cholecystectomy between August 2017 and October 2018 were recruited and randomized into Handout Assisted Consent (HC) and Verbal Consent (VC) group. The HC group was given an adjunct handout on laparoscopic cholecystectomy during consent process in addition to the standard verbal consent. A validated open-ended verbal understanding and recall questionnaire was administered to all patients in both groups at Day 1, 30 and 90 after surgery. Patient satisfaction of the consent process was evaluated with Likert scale.

    RESULTS: A total of 79 patients were enrolled, 41 patients and 38 patients in VC and HC groups respectively. Level of understanding among patients were equal and consistent across time in both groups (P > 0.05). There was significant decline (P  0.05).

    CONCLUSION: There is good consistent understanding of the surgery in both groups. However, recall of specific surgical consent items decreased significantly over time in both groups. Handouts may have increased satisfaction among patients but did not improve recall in this preliminary study.

    TRIAL REGISTRATION: MREC No.:201783-5468.

  12. Malik AA, Rajandram R, Tah PC, Hakumat-Rai VR, Chin KF
    J Crit Care, 2016 Apr;32:182-8.
    PMID: 26777745 DOI: 10.1016/j.jcrc.2015.12.008
    Gut failure is a common condition in critically ill patients in the intensive care unit (ICU). Enteral feeding is usually the first line of choice for nutrition support in critically ill patients. However, enteral feeding has its own set of complications such as alterations in gut transit time and composition of gut eco-culture. The primary aim of this study was to investigate the effect of microbial cell preparation on the return of gut function, white blood cell count, C-reactive protein levels, number of days on mechanical ventilation, and length of stay in ICU. A consecutive cohort of 60 patients admitted to the ICU in University Malaya Medical Centre requiring enteral feeding were prospectively randomized to receive either treatment (n = 30) or placebo (n = 30). Patients receiving enteral feeding supplemented with a course of treatment achieved a faster return of gut function and required shorter duration of mechanical ventilation and shorter length of stay in the ICU. However, inflammatory markers did not show any significant change in the pretreatment and posttreatment groups. Overall, it can be concluded that microbial cell preparation enhances gut function and the overall clinical outcome of critically ill patients receiving enteral feeding in the ICU.
  13. Morais C, Rajandram R, Blakeney JS, Iyer A, Suen JY, Johnson DW, et al.
    PLoS One, 2021;16(3):e0248983.
    PMID: 33765016 DOI: 10.1371/journal.pone.0248983
    Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.
  14. Mujtaba G, Shuib L, Raj RG, Rajandram R, Shaikh K
    J Forensic Leg Med, 2018 Jul;57:41-50.
    PMID: 29801951 DOI: 10.1016/j.jflm.2017.07.001
    OBJECTIVES: Automatic text classification techniques are useful for classifying plaintext medical documents. This study aims to automatically predict the cause of death from free text forensic autopsy reports by comparing various schemes for feature extraction, term weighing or feature value representation, text classification, and feature reduction.

    METHODS: For experiments, the autopsy reports belonging to eight different causes of death were collected, preprocessed and converted into 43 master feature vectors using various schemes for feature extraction, representation, and reduction. The six different text classification techniques were applied on these 43 master feature vectors to construct a classification model that can predict the cause of death. Finally, classification model performance was evaluated using four performance measures i.e. overall accuracy, macro precision, macro-F-measure, and macro recall.

    RESULTS: From experiments, it was found that that unigram features obtained the highest performance compared to bigram, trigram, and hybrid-gram features. Furthermore, in feature representation schemes, term frequency, and term frequency with inverse document frequency obtained similar and better results when compared with binary frequency, and normalized term frequency with inverse document frequency. Furthermore, the chi-square feature reduction approach outperformed Pearson correlation, and information gain approaches. Finally, in text classification algorithms, support vector machine classifier outperforms random forest, Naive Bayes, k-nearest neighbor, decision tree, and ensemble-voted classifier.

    CONCLUSION: Our results and comparisons hold practical importance and serve as references for future works. Moreover, the comparison outputs will act as state-of-art techniques to compare future proposals with existing automated text classification techniques.

  15. Mujtaba G, Shuib L, Raj RG, Rajandram R, Shaikh K, Al-Garadi MA
    J Biomed Inform, 2018 06;82:88-105.
    PMID: 29738820 DOI: 10.1016/j.jbi.2018.04.013
    Text categorization has been used extensively in recent years to classify plain-text clinical reports. This study employs text categorization techniques for the classification of open narrative forensic autopsy reports. One of the key steps in text classification is document representation. In document representation, a clinical report is transformed into a format that is suitable for classification. The traditional document representation technique for text categorization is the bag-of-words (BoW) technique. In this study, the traditional BoW technique is ineffective in classifying forensic autopsy reports because it merely extracts frequent but discriminative features from clinical reports. Moreover, this technique fails to capture word inversion, as well as word-level synonymy and polysemy, when classifying autopsy reports. Hence, the BoW technique suffers from low accuracy and low robustness unless it is improved with contextual and application-specific information. To overcome the aforementioned limitations of the BoW technique, this research aims to develop an effective conceptual graph-based document representation (CGDR) technique to classify 1500 forensic autopsy reports from four (4) manners of death (MoD) and sixteen (16) causes of death (CoD). Term-based and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) based conceptual features were extracted and represented through graphs. These features were then used to train a two-level text classifier. The first level classifier was responsible for predicting MoD. In addition, the second level classifier was responsible for predicting CoD using the proposed conceptual graph-based document representation technique. To demonstrate the significance of the proposed technique, its results were compared with those of six (6) state-of-the-art document representation techniques. Lastly, this study compared the effects of one-level classification and two-level classification on the experimental results. The experimental results indicated that the CGDR technique achieved 12% to 15% improvement in accuracy compared with fully automated document representation baseline techniques. Moreover, two-level classification obtained better results compared with one-level classification. The promising results of the proposed conceptual graph-based document representation technique suggest that pathologists can adopt the proposed system as their basis for second opinion, thereby supporting them in effectively determining CoD.
  16. Mujtaba G, Shuib L, Raj RG, Rajandram R, Shaikh K, Al-Garadi MA
    PLoS One, 2017;12(2):e0170242.
    PMID: 28166263 DOI: 10.1371/journal.pone.0170242
    OBJECTIVES: Widespread implementation of electronic databases has improved the accessibility of plaintext clinical information for supplementary use. Numerous machine learning techniques, such as supervised machine learning approaches or ontology-based approaches, have been employed to obtain useful information from plaintext clinical data. This study proposes an automatic multi-class classification system to predict accident-related causes of death from plaintext autopsy reports through expert-driven feature selection with supervised automatic text classification decision models.

    METHODS: Accident-related autopsy reports were obtained from one of the largest hospital in Kuala Lumpur. These reports belong to nine different accident-related causes of death. Master feature vector was prepared by extracting features from the collected autopsy reports by using unigram with lexical categorization. This master feature vector was used to detect cause of death [according to internal classification of disease version 10 (ICD-10) classification system] through five automated feature selection schemes, proposed expert-driven approach, five subset sizes of features, and five machine learning classifiers. Model performance was evaluated using precisionM, recallM, F-measureM, accuracy, and area under ROC curve. Four baselines were used to compare the results with the proposed system.

    RESULTS: Random forest and J48 decision models parameterized using expert-driven feature selection yielded the highest evaluation measure approaching (85% to 90%) for most metrics by using a feature subset size of 30. The proposed system also showed approximately 14% to 16% improvement in the overall accuracy compared with the existing techniques and four baselines.

    CONCLUSION: The proposed system is feasible and practical to use for automatic classification of ICD-10-related cause of death from autopsy reports. The proposed system assists pathologists to accurately and rapidly determine underlying cause of death based on autopsy findings. Furthermore, the proposed expert-driven feature selection approach and the findings are generally applicable to other kinds of plaintext clinical reports.

  17. Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.
    Pathology, 2018 Aug;50(5):511-518.
    PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003
    Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.
  18. Ng KL, Del Vecchio SJ, Samaratunga H, Morais C, Rajandram R, Vesey DA, et al.
    Pathology, 2018 Aug;50(5):504-510.
    PMID: 29970253 DOI: 10.1016/j.pathol.2018.01.007
    One of the challenges in differentiating chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is overlapping morphology between the two subtypes. The aim of this study was to investigate the usefulness of expression of leptin (Ob) and its receptor (ObR) in discriminating chRCC from RO. Sections from paraffin-embedded, formalin-fixed tumour nephrectomy specimens of 45 patients, made up of 30 chRCC (15 eosinophilic variant and 15 non-eosinophilic variant) and 15 RO, were used in this study. Samples (30) of clear cell RCC (ccRCC), the most common histological subtype, were used to verify staining patterns found by others in our cohort of Australasian patients. Matched morphologically normal non-cancer kidney tissues were included for each specimen. Sections were batch-immunostained using antibodies against Ob and ObR. Stained sections were digitally scanned using Aperio ImageScope, and the expression pattern of Ob and ObR was studied. In this cohort, male to female ratio was 2:1; median age was 64 (45-88 years); and median tumour size was 3.8 cm (range 1.2-18 cm). There were 47 (62.7%) T1, seven T2, 20 T3 and one T4 stage RCC. Two patients with ccRCC presented with metastases. Nuclear expression of Ob was significantly higher in RO compared with chRCC. The increased nuclear expression of Ob in RO compared with chRCC may be a useful aid in the difficult histological differentiation of RO from chRCC, especially eosinophilic variants of chRCC.
  19. Pailoor J, Rajandram R, Yap NY, Ng KL, Wang Z, Iyengar KR
    Indian J Pathol Microbiol, 2013 Apr-Jun;56(2):98-102.
    PMID: 24056643 DOI: 10.4103/0377-4929.118688
    Chromosome 7 aberrations in renal cell carcinoma (RCC) have been reported in papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC). However, the implication of these anomalies on prognosis and survival is still unclear. RCC Chromosome 7 aberrations have commonly been detected by fluorescent in situ hybridization and chromogenic in situ hybridization but not silver in situ hybridization (SISH).
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