Displaying publications 1 - 20 of 38 in total

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  1. 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.

  2. Yap NY, Ong TA, Pailoor J, Gobe G, Rajandram R
    Biomarkers, 2023 Feb;28(1):24-31.
    PMID: 36315054 DOI: 10.1080/1354750X.2022.2142292
    Purpose: CD14-positive tumour and immune cells have been implicated in cancer progression. This study evaluated the prognostic significance of CD14 immunostaining in clear cell renal cell carcinoma (ccRCC) compared to the adjacent non-cancer kidney, and serum soluble CD14 (sCD14) levels in patients versus controls.Methods: Immunohistochemistry was performed for CD14 on ccRCC and the corresponding adjacent non-cancer kidney tissue from 88 patients. Staining intensity was determined using Aperio ImageScope morphometry. Serum sCD14 was evaluated for 39 ccRCC patients and 38 non-cancer controls using ELISA. CD14 levels were compared with tumour characteristics and survival status.Results: CD14 overall and nuclear immunostaining was higher in ccRCC compared to the adjacent non-cancer kidney tissue. CD14 nuclear immunostaining in the adjacent non-cancer kidney was significantly associated with advanced stage and adverse RCC survival prognosis. Serum sCD14 concentration was elevated in ccRCC patients compared to non-cancer controls and was also significantly associated with tumour stage and worse survival prognosis. Higher CD14 expression, in particular CD14 positive immune cell infiltrates found in the adjacent non-RCC kidney tissue, were associated with tumour progression and poorer prognosis.Conclusion: The levels of CD14 in non-RCC adjacent kidney and serum could be potential prognostic indicators.
  3. 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.
  4. Tamalvanan V, Rajandram R, Kuppusamy S
    Medicine (Baltimore), 2022 Sep 16;101(37):e30425.
    PMID: 36123909 DOI: 10.1097/MD.0000000000030425
    Pain control is a major determinant for successful stone clearance in extracorporeal shockwave lithotripsy (ESWL) for urolithiasis. Pain perception during ESWL may be influenced by patient factors like gender, age, body habitus and anxiety level, and stone related factors like size, laterality and location of stone. We investigated in general, the confounding patient and stone factors influencing pain perception during ESWL with importance given to procedural anxiety in first and the subsequent session of ESWL. This was a prospective observational study of all new consecutive patients who underwent ESWL for a period of 1 year at a tertiary Urological Centre. Demographic and stone anthropometry were analyzed. Pre-procedural anxiety was assessed prior to procedure using hospital anxiety and depression score (HADS) and pain was scored using numerical rating scale-11 at baseline, 30-minutes (i.e., during) and 24 hours after ESWL. Univariate and multivariate analysis for confounding factors included HADs were performed for pain perception. A P value 
  5. Rajandram R, Koong JK, Quek KF, Lee EG, Razack AHA, Kuppusamy S
    Clin Endocrinol (Oxf), 2022 Feb 02.
    PMID: 35107834 DOI: 10.1111/cen.14682
    OBJECTIVE: To investigate non-urological patients with multiple comorbidities for factors contributing towards differences in testosterone concentration in multiethnic Malaysian men.

    DESIGN: An observational study.

    PATIENTS: Sexually active men, ≥40 years, with no known urological problems, were recruited at the phlebotomy clinic at our centre.

    MEASUREMENTS: A brief history along with latest fasting lipid profile and plasma glucose levels were obtained. An Aging Male Symptoms questionnaire was administered; waist circumference (WC) and serum testosterone concentration were measured.

    STATSTICAL ANALYSIS: Analysis of testosterone concentration between Malay, Indian and Chinese men was performed. Statistical tests such as analysis of variance, χ2 test, univariate and multivariable regression were performed. Any p  .05). In the multivariable analysis only Malay ethnicity, WC ≥ 90 cm and low high-density lipoprotein (HDL) were associated with lower testosterone concentration.

    CONCLUSION: In this study, Malaysian men of Malay origin had lower testosterone concentration compared with Indian and Chinese men. WC and low HDL were also associated with lower testosterone concentrations.

  6. Wong L, Rajandram R, Allorto N
    Burns, 2021 Jul 07.
    PMID: 34303572 DOI: 10.1016/j.burns.2021.07.001
    INTRODUCTION: While the benefits of early excision in burn surgery are clear, the advantages may be lost in low income countries with limited resources. It is important to identify the right timing of excision in different groups of patients, particularly those in low-income countries (LIC), as the burden of disease contributes to the highest global mortality and has the least resources. This systematic review and meta-analysis aims to determine the timing of excision in LICs and the outcomes associated with surgery: (1) mortality, (2) sepsis and (3) length of stay (LOS) compared to high income countries (HICs).

    METHODOLOGY: The PRISMA guidelines and MOOSE checklist were followed for this review. Publications in English from year 1990 to 2017 that included data on the timing and type of burn surgery and outcomes were included. Searches were done using Web of Science, Cochrane collaboration and Pubmed using keywords "Burn and surgery", "Burn and excision", "Burn and excision and grafting" and "burn and skin grafting". Trial quality was evaluated using the Newcastle-Ottawa scale. Outcomes compared for early and late excisions were length of stay (LOS), sepsis and mortality between LICs and HICs.

    RESULTS: From 278 citations, we selected 41 for full text evaluation, and identified 16 eligible trials. LOS is shorter in early excision compared to late excision in both LICs and HICs. Mortality is lower in late excision compared to early excision in both LICs and HICs. Further subgroup analysis of elderly patients in HICs confirmed that mortality is lower in late excision and unchanged if the elderly are excluded. Early excision reduces sepsis in both LIC and HIC.

    DISCUSSION: The variable definitions of age, timing of excision, variable nature of % TBSA comparison, mixed inclusion of inhalation injury, co-morbidities and unquantified access to resources make the data difficult to interpret and it is not possible to draw accurate conclusions on the role of early excision for burns in low-middle income countries. A prospective study is needed in order to answer this question.

  7. 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.

  8. 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.

  9. 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.
  10. 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.
  11. Perumal K, Mun KS, Yap NY, Razack AHA, Gobe GC, Ong TA, et al.
    Biomed Res Int, 2020;2020:3682086.
    PMID: 32802842 DOI: 10.1155/2020/3682086
    Background: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer.

    Objective: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant.

    Results: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC.

    Conclusion: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

  12. Samberkar S, Rajandram R, Mun KS, Samberkar P, Danaee M, Zulkafli IS
    Malays J Pathol, 2019 Dec;41(3):233-242.
    PMID: 31901907
    INTRODUCTION: Tissue biomarker carbonic anhydrase IX (CAIX) is purported to have prognostic value for renal cell carcinoma (RCC) but contradicting findings from previous studies have also been documented. This study aims to perform a systematic review and meta-analysis on the role of CAIX in RCC disease progression.

    MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.

    RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.

    CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.

  13. Yap NY, Yap FN, Perumal K, Rajandram R
    Biomarkers, 2019 Sep;24(6):607-614.
    PMID: 31215811 DOI: 10.1080/1354750X.2019.1634763
    Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels. Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC. Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan. Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels. Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.
  14. Perumal K, Huin WK, Yap NY, Ong TA, Gobe GC, Rajandram R
    Med Hypotheses, 2019 Aug;129:109239.
    PMID: 31371068 DOI: 10.1016/j.mehy.2019.109239
    Renal cell carcinoma (RCC) is the commonest from of renal neoplasm. Although surgery is a successful curative treatment for localized RCC, most patients are diagnosed with advanced or metastatic RCC, which has poor prognosis. RCC is classified by stage and grade using tissue samples. Whilst these provide good prognostic information, they are not very useful for early detection. Proteins that are dysregulated in patient's serum can be a valuable alternative and less invasive biomarker for early detection of the disease. For this reason, a hypothesis was formed that leptin is a possible biomarker for early detection and prognostication of RCC. The literature has disparate results on the usefulness of leptin as a biomarker for the early detection of RCC. Hence, a systematic review and a meta-analysis was carried out to investigate whether serum leptin could be a reliable diagnostic and prognostic factor in RCC patients. Literature on the available cohort and case-control studies on serum leptin in RCC was searched in electronic databases and included to evaluate this adipokine in the progression of RCC. The relevant studies were evaluated for the diagnostic and prognostic value of leptin in RCC patients. Overall, only 6 original research studies matched selection criteria and were included for meta-analysis. This study was hypothesised that; leptin might be a useful biomarker for early detection and prognostication of RCC. However, the data were presented in this study did not support our hypothesis. Serum leptin levels in RCC patients do not strongly associate with the development or progression of RCC, thus cannot act as a biomarker for early detection in RCC in patients. Extending our hypothesis further to include levels of obesity and RCC development may be worthwhile, but studies are currently limited.
  15. Yap NY, Ong TA, Morais C, Pailoor J, Gobe GC, Rajandram R
    Cell Biol Int, 2019 Jun;43(6):715-725.
    PMID: 31062478 DOI: 10.1002/cbin.11150
    Renal cell carcinoma (RCC) is one of the most lethal urogenital cancers and effective treatment of metastatic RCC remains an elusive target. Cell lines enable the in vitro investigation of molecular and genetic changes leading to renal carcinogenesis and are important for evaluating cellular drug response or toxicity. This study details a fast and easy protocol of establishing epithelial and fibroblast cell cultures or cell lines concurrently from renal cancer nephrectomy tissue. The protocol involves mechanical disaggregation, collagenase digestion and cell sieving for establishing epithelial cells while fibroblast cells were grown from explants. This protocol has been modified from previous published reports with additional antibiotics and washing steps added to eliminate microbial contamination from the surgical source. Cell characterisation was carried out using immunofluorescence and quantitative polymerase chain reaction. Eleven stable epithelial renal tumour cell lines of various subtypes, including rare subtypes, were established with a spontaneous immortalisation rate of 21.6% using this protocol. Eight fibroblast cell cultures grew successfully but did not achieve spontaneous immortalisation. Cells of epithelial origin expressed higher expressions of epithelial markers such as pan-cytokeratin, cytokeratin 8 and E-cadherin whereas fibroblast cells expressed high α-smooth muscle actin. Further mutational analysis is needed to evaluate the genetic or molecular characteristics of the cell lines.
  16. Rajandram R, Perumal K, Yap NY
    Transl Androl Urol, 2019 May;8(Suppl 2):S138-S146.
    PMID: 31236331 DOI: 10.21037/tau.2018.11.10
    Obesity is a recognized risk factor for renal cell carcinoma (RCC) the commonest form of kidney cancer. Both obesity and RCC are serious diseases with increasing incidence yearly. This review examined certain obesity associated measurements and adipokines as detection/prognostic indicators for RCC. The obesity related measurements such as body mass index (BMI), waist circumstance (WC), waist-hip ratio (WHR) in predicting RCC are valid when used in conjunction with other risk factors such as age and sex or with histological findings. The adipokine adiponectin holds promising outcomes as a predictive marker in assessing the risk of developing RCC. In addition, tissue leptin/leptin receptor may be a distinguishing marker for RCC subtypes. However, circulating leptin may not be a suitable detection or prognostic biomarker for RCC. The other less investigated adipokines; omentin, visfatin, apelin and resistin are also expressed in RCC but their prognostic capabilities are still inconclusive. BMI, WC and adipokines may be useful additions in a nomogram which includes TNM staging and pathological grading system to detect, confirm and follow-up RCC cases.
  17. 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.

  18. 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.
  19. 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.
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