Displaying publications 1 - 20 of 38 in total

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  1. Tan CK, Said S, Rajandram R, Wang Z, Roslani AC, Chin KF
    World J Surg, 2016 08;40(8):1985-92.
    PMID: 27098538 DOI: 10.1007/s00268-016-3499-9
    INTRODUCTION: Disruption of normal gut function is a common side effect post abdominal surgery. It may result in reduced tolerance to oral nutrition and progress to postoperative ileus. Microbial cell preparation is beneficial as a pre-surgical nutritional supplement to aid in bowel recovery and promote the return of normal gut function following abdominal surgery. The aim of this study was to evaluate the efficacy of pre-surgical administration of microbial cell preparation in promoting the return of normal gut function.

    METHOD: The study is a randomized, double-blind, placebo-controlled trial. In total, 40 patients were recruited. Patients were randomized to receive either microbial cell preparation (n = 20) or placebo (n = 20) for 7 days prior to elective surgery. The primary end point was the time to return of normal gut function, while the secondary end point was the duration of hospital stay.

    RESULTS: The treatment group demonstrated significantly faster return of normal gut function with a median of 108.5 h (80-250 h) which was 48 h earlier than the placebo group at a median of 156.5 h (94-220 h), p = 0.022. The duration of hospital stay in the treatment group was also shorter at a median of 6.5 days (4-30 days), in comparison to the placebo group at 13 days (5-25 days), p = 0.012.

    CONCLUSION: Pre-surgical administration of microbial cell preparation promotes the return of normal gut function in patients after colorectal cancer surgery, thus associated with faster recovery and shorter duration of hospital stay.

  2. 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.
  3. 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.

  4. 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.

  5. Rajandram R, Yap NY, Ong TA, Mun KS, Mohamad Wali HA, Hasan MS, et al.
    Malays J Pathol, 2017 Apr;39(1):47-53.
    PMID: 28413205 MyJurnal
    INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake.

    METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder.

    RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys.

    CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.

  6. 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.

  7. 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.

  8. Ramli R, Abdul Rahman R, Abdul Rahman N, Abdul Karim F, Krsna Rajandram R, Mohamad MS, et al.
    J Craniofac Surg, 2008 Mar;19(2):316-21.
    PMID: 18362705 DOI: 10.1097/SCS.0b013e318163f94d
    Motorcycle casualties represent significant number in road traffic accidents in Malaysia, and among all the injuries, facial injuries pose many significant problems physiologically, functionally, and aesthetically. The aim of this study was to analyze the pattern of maxillofacial as well as other injuries in motorcyclists who were seen at Hospital Universiti Kebangsaan Malaysia.Patients' records from January 2004 to December 2005 were reviewed. Data related to demographics, vehicle/object involved in collision, involvement as a rider or pillion, whether a helmet was worn or not, location of injuries on the face/facial bones, and other associated injuries were collected.A total of 113 cases of motorcycle accidents were recorded; 106 males and 7 females were involved. Mean age was 25.8 years. Among all the races, Malay had the highest involvement (72.3%), followed by Chinese (14.3%), Indians (8.9%), and others (5.4%). The types of collision were either a single-vehicle collision (i.e., skidded) or with another vehicle/s or object (e.g., tree, stone, or lamppost). The injuries were mainly seen on the lower face (46.9%) followed by midface (25.7%) and a combination of the midface and lower face (15%) and others (12.4%). The most frequent other associated injuries recorded were orthopedic and head injuries.
  9. 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.

  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. 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.

  12. 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.
  13. Rajandram R, Yap NY, Pailoor J, Razack AH, Ng KL, Ong TA, et al.
    Pathology, 2014 Oct;46(6):518-22.
    PMID: 25158810 DOI: 10.1097/PAT.0000000000000145
    Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. We have previously described decreased tumour necrosis factor receptor-associated factor-1 (TRAF-1) in RCC compared with paired normal kidney in a patient cohort in Australia. In the present study, TRAF-1 expression in clear cell RCC (ccRCC) and normal kidney was again compared, but in a cohort from University Malaya Medical Centre. Serum TRAF-1 was also evaluated in RCC and normal samples.Immunohistochemistry with automated batch staining and Aperio ImageScope morphometry was used to compare TRAF-1 in 61 ccRCC with paired normal kidney tissue. Serum from 15 newly diagnosed and untreated ccRCC and 15 healthy people was tested for TRAF-1 using ELISA.In this cohort, TRAF-1 was highly expressed in proximal tubular epithelium of normal kidney, and significantly decreased in ccRCC tissue (p 
  14. 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.
  15. 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.
  16. 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 
  17. 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.
  18. Rajandram R, Razack AH, Ng KL, Gobe GC
    J Kidney Cancer VHL, 2016;3(1):1-11.
    PMID: 28326275 DOI: 10.15586/jkcvhl.2016.47
    Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of "inhibitor of caspase-activated DNase" (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.
  19. 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.
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