Displaying publications 1 - 20 of 56 in total

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  1. Cheng JY, Samudram H, Lee Lai Ling C, Nadarajan VS
    Transfus Med, 2022 Dec;32(6):484-491.
    PMID: 36239101 DOI: 10.1111/tme.12924
    OBJECTIVES: To evaluate the performance and utility of a time-temperature indicator (TTI) to determine the cumulative exposure time (CET) of red cell components (RCC) to temperatures above 10°C occurring within and outside the transfusion laboratory.

    BACKGROUND AND OBJECTIVES: Blood centres often use the '30 or 60-min rule' for accepting RCC exposed to room temperature (RT) back into inventory. Effective monitoring of these temperature deviations is however lacking.

    MATERIALS AND METHODS: A Timestrip PLUS® TP153 10°C (TS + 10) TTI was attached to RCC units after preparation of the unit in the blood bank or on issue to the ward, to track the CET > 10°C during laboratory processing and outside the transfusion laboratory.

    RESULTS: The mean CET of 153 RCC tracked within the laboratory was 56 min. Sixty-four (41.8%) and 34 (22.2%) of RCC had core temperature (CT) >10°C for more than 30 and 60 min, respectively. Among the 69 RCC that were returned unused, 27 (39.1%), 17 (24.6%) and 5 (7.2%) RCC units had CT >10°C for more than 30, 60 and 120 min respectively.

    CONCLUSION: A large proportion of RCC have CT >10°C exceeding 30 min during handling within the transfusion laboratory, as well as when RCC are returned unused from transfusion locations. Corrective measures should be implemented to better manage the cold chain to avoid undesirable consequences to blood transfusion. A temperature sensitive device that can also indicate CET can be employed to objectively monitor the period that RCC remained at a CT that exceeds 10°C.

    Matched MeSH terms: Carcinoma, Renal Cell*
  2. Chan VW, Tan WS, Leow JJ, Tan WP, Ong WLK, Chiu PK, et al.
    World J Urol, 2021 Dec;39(12):4295-4303.
    PMID: 34031748 DOI: 10.1007/s00345-021-03734-1
    PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era.

    METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared.

    RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p 

    Matched MeSH terms: Carcinoma, Renal Cell/mortality*; Carcinoma, Renal Cell/pathology; Carcinoma, Renal Cell/surgery*
  3. Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.
    BMC Cancer, 2021 Sep 14;21(1):1021.
    PMID: 34521387 DOI: 10.1186/s12885-021-08738-z
    BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

    METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

    RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving  10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).

    CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

    Matched MeSH terms: Carcinoma, Renal Cell/drug therapy*; Carcinoma, Renal Cell/ethnology; Carcinoma, Renal Cell/mortality; Carcinoma, Renal Cell/pathology
  4. Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF
    Malays J Pathol, 2021 Apr;43(1):69-73.
    PMID: 33903308
    Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
    Matched MeSH terms: Carcinoma, Renal Cell
  5. Marafi F, Sasikumar A, Aldaas M, Esmail A
    Clin Nucl Med, 2021 Jan;46(1):e65-e67.
    PMID: 33181733 DOI: 10.1097/RLU.0000000000003354
    A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.
    Matched MeSH terms: Carcinoma, Renal Cell/complications; Carcinoma, Renal Cell/pathology*
  6. 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.
    Matched MeSH terms: Carcinoma, Renal Cell/genetics; Carcinoma, Renal Cell/metabolism*; Carcinoma, Renal Cell/pathology*
  7. Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, et al.
    Eur Urol, 2020 10;78(4):592-602.
    PMID: 32305170 DOI: 10.1016/j.eururo.2020.03.020
    BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described.

    OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT.

    DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019.

    SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals.

    MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed.

    RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed.

    CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation.

    PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

    Matched MeSH terms: Carcinoma, Renal Cell/secondary*
  8. Chen EJ, Tan TH, Chew MT, Chye PC
    Clin Nucl Med, 2020 Jul;45(7):e317-e319.
    PMID: 32404702 DOI: 10.1097/RLU.0000000000003053
    Recent case reports and series have demonstrated the usefulness of Ga/F-PSMA PET/CT in restaging recurrent renal cancer after nephrectomy. We presented a case of a patient with renal mass who had undergone both F-FDG and Ga-PSMA PET/CT for diagnosis and staging. Concordant tracer uptake in the primary tumor and metastatic lesions was demonstrated by both radiotracers. Final histopathological reports revealed clear cell renal cell carcinoma. Furthermore, unusual left metacarpal bone metastasis was also detected.
    Matched MeSH terms: Carcinoma, Renal Cell/pathology
  9. Khoo ACH, Cheong YT
    World J Nucl Med, 2020 01 14;19(1):89-91.
    PMID: 32190033 DOI: 10.4103/wjnm.WJNM_14_19
    Renal cell carcinomas (RCCs) commonly metastasize to the lungs and bones and rarely to the parathyroid, maxillary sinus, and adrenals. It is indeed very rare to have these all these metastases occurring simultaneously in an individual. We share a case of 67-year-old woman provisionally treated for parathyroid carcinoma but subsequently found to actually have metastatic RCC to the left maxillary sinus, parathyroid, lungs, and adrenals on 18F-fluorodeoxyglucose positron emission tomography-computed tomography.
    Matched MeSH terms: Carcinoma, Renal Cell
  10. 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.

    Matched MeSH terms: Carcinoma, Renal Cell/metabolism*; Carcinoma, Renal Cell/pathology
  11. 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.

    Matched MeSH terms: Carcinoma, Renal Cell/diagnosis; Carcinoma, Renal Cell/pathology*
  12. 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.
    Matched MeSH terms: Carcinoma, Renal Cell/blood; Carcinoma, Renal Cell/diagnosis*; Carcinoma, Renal Cell/genetics; Carcinoma, Renal Cell/pathology
  13. 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.
    Matched MeSH terms: Carcinoma, Renal Cell
  14. Nyanti L, Samsudin A, Tiong IK
    J Med Case Rep, 2019 Jun 21;13(1):188.
    PMID: 31221202 DOI: 10.1186/s13256-019-2122-8
    BACKGROUND: Leser-Trélat syndrome, which manifests as eruptive multiple seborrheic keratoses, is a rare paraneoplastic sign. Hyponatremia in the elderly population is an often overlooked but potentially sinister biochemical abnormality. Cancer-related causes of hyponatremia include syndrome of inappropriate antidiuretic hormone secretion, cerebral or renal salt wasting, and adrenal dysfunction. We report a case of an elderly man who presented with both syndrome of inappropriate antidiuretic hormone secretion and Leser-Trélat syndrome, and was eventually found to have renal malignancy.

    CASE PRESENTATION: A 74-year-old indigenous Malaysian man with underlying chronic kidney disease presented with recurrent admissions for hyponatremia with parameters indicative of syndrome of inappropriate antidiuretic hormone secretion, constitutional symptoms, and diffuse skin lesions suggestive of multiple seborrheic keratoses. A radiological workup revealed metastatic renal cell carcinoma with evidence of metastasis to the brain, adrenal glands, bone, and lungs.

    CONCLUSIONS: To the best of our knowledge, renal malignancy presenting as syndrome of inappropriate antidiuretic hormone secretion and Leser-Trélat concurrently is rare. The causes of hyponatremia in the elderly, approach to investigation, and value as a poor prognostic marker in malignancy are highlighted. We also discuss Leser-Trélat syndrome, its pathophysiology, and its possible implications on clinical practice.

    Matched MeSH terms: Carcinoma, Renal Cell/complications*; Carcinoma, Renal Cell/secondary
  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.
    Matched MeSH terms: Carcinoma, Renal Cell/metabolism; Carcinoma, Renal Cell/pathology*
  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.
    Matched MeSH terms: Carcinoma, Renal Cell
  17. Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
    Matched MeSH terms: Carcinoma, Renal Cell/genetics*; Carcinoma, Renal Cell/pathology
  18. Caunter G, Faeez Md Noh MS, Safri LS, Kumar K, Md Idris MA, Harunarashid H, et al.
    EJVES Short Rep, 2019;44:19-22.
    PMID: 31453386 DOI: 10.1016/j.ejvssr.2019.06.003
    Introduction: The development of metastatic renal cell carcinoma (RCC) many years after a nephrectomy is not common but has been reported. A metastasis appearing as a hypervascular tumour, mimicking an arteriovenous malformation (AVM), is a highly unusual phenomenon, with a biopsy required for diagnostic confirmation. Surgery is an option for a solitary metastatic lesion amenable to complete excision, with proven survival benefits. However, widespread metastatic disease carries a very poor prognosis, and is best treated with systemic agents such as anti-angiogenic drugs or tyrosine kinase inhibitors.

    Report: A 58 year old man developed an AVM mimicking a vascular tumour within his left brachioradialis muscle 10 years after a nephrectomy for RCC. Ultrasound and magnetic resonance imaging did not reveal any suspicious features of the vascular lesion.The lesion was successfully removed surgically, and was later proven histopathologically to be metastatic RCC. Further imaging showed widespread metastatic disease, and the patient survived only 15 months after receiving tyrosine kinase inhibitor therapy.

    Discussion: This case report aims to highlight a few important points: RCC metastases may be hypervascular, mimicking an AVM. A long disease free interval does not necessarily exclude recurrence or metastasis, as in this case, therefore long term surveillance is recommended. A high index of suspicion must be maintained to avoid delay in treatment, and biopsy of any suspicious lesion for histological examination is mandatory, albeit after many years of cancer remission. Whole body imaging with computed tomography or positron emission tomography computed tomography may detect clinically occult recurrence or metastases, and is important to guide further treatment.

    Matched MeSH terms: Carcinoma, Renal Cell
  19. Mohtarrudin N, Ghazali R, Md Roduan MR
    Malays J Pathol, 2018 Dec;40(3):313-318.
    PMID: 30580362
    INTRODUCTION: Cyclooxygenase-2 (COX-2) promotes carcinogenesis by inducing proliferation and angiogenesis while decreasing apoptosis and immunosuppressive activity. It is overexpressed in many malignancies including renal cell carcinoma (RCC). The aim of this study was to investigate COX-2 expression in clear cell RCC and its association with tumour grades and demographic parameters.

    MATERIALS AND METHODS: Thirty-six clear cell RCC cases were selected. There were 21 (58.3%) men and 15 (41.7%) women with median age of 56.6 years (range: 16-74 years). Chinese constituted 16 (44.4%) of the cases; Malays 14 (38.9%) cases and Indian 6 (16.7%) cases. There were 6 (16.7%) grade 1, 20 (55.6%) grade 2, 10 (27.8%) grade 3 and none was grade 4. The paraffin embedded tissues were cut at 4 μm thick and stained with COX-2 monoclonal antibody.

    RESULTS: Eighteen (50%) of the RCC cases were immunopositive, of which all showed strong positivity. The immunopositive cases showed cytoplasmic membrane positivity.

    CONCLUSION: There was no significant association between COX-2 expression with grade, age, sex and ethnicity (p=0.457, p=0.054, p=0.389 and p=0.568 respectively). Strong positivity of COX-2 suggest that COX-2 may play a role in cell proliferation and in carcinogenesis.

    Matched MeSH terms: Carcinoma, Renal Cell/metabolism*; Carcinoma, Renal Cell/pathology
  20. Scelo G, Muller DC, Riboli E, Johansson M, Cross AJ, Vineis P, et al.
    Clin Cancer Res, 2018 Nov 15;24(22):5594-5601.
    PMID: 30037816 DOI: 10.1158/1078-0432.CCR-18-1496
    Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis.Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival.Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44-2.03, P = 4.1 × 10-23], corresponding to an IRR of 63.3 (95% CI, 16.2-246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594-601. ©2018 AACR.
    Matched MeSH terms: Carcinoma, Renal Cell/blood; Carcinoma, Renal Cell/diagnosis
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