Latest Research News on Kidney Cancer : Jan 2022

Kidney cancer

In the USA, the incidence of kidney cancer has increased 43% since 1973. The risk of the disorder is higher in men than in women and increases with age. The von Hippel-Lindau tumour-suppressor gene is inactivated in over 75% of sporadic cases. Metastatic disease is present in 20–30% of patients at diagnosis. Early-stage kidney cancer is treated with a radical nephrectomy, but under certain circumstances a partial nephrectomy may be done. Tumour thrombus into the vena cava or right atrium requires thoracotomy and hypothermic circulatory arrest for successful removal of the tumour, but should not be done if extensive nodal or frank metastatic disease is present. Interleukin-2 is the systemic therapy of choice for metastatic disease at present, with long-term relapse-free survival of 5–8%. Several treatments including anti-angiogenesis drugs, cyclin-dependent kinase inhibitors, and differentiating agents are being actively investigated. Fluorouracil has a 10–15% response rate, and surgical excision of isolated metastases should always be considered. Therapy for metastatic renal cancer remains inadequate, but recent developments in basic and clinical research suggest future improvement.[1]

Epidemiology and risk factors for kidney cancer

After more than two decades of rising rates, in recent years the total kidney cancer incidence worldwide has shown signs of stabilizing, or even decreasing. In adults, kidney cancer consists of renal cell carcinoma (RCC), the predominant form, and renal transitional cell carcinoma (RTCC); these types primarily arise in the renal parenchyma and renal pelvis, respectively. Although temporal trends by kidney cancer type are not well established worldwide, incidence of RCC in the US has continued to rise, mainly for early-stage tumors, while that of RTCC has declined, and total kidney cancer mortality rates have leveled. Stabilization of kidney cancer mortality rates has also been reported in Europe. These trends are consistent with reports of increasing incidental diagnoses and a downward shift in tumor stage and size in clinical series. The changing prevalence of known risk factors for RCC, including cigarette smoking, obesity, and hypertension, is also likely to affect incidence trends, although their relative impact may differ between populations. Accumulating evidence suggests an etiologic role in RCC for physical activity, alcohol consumption, occupational exposure to trichloroethylene, and high parity among women, but further research is needed into the potential causal effects of these factors. Genetic factors and their interaction with environmental exposures are believed to influence risk of developing RCC, but a limited number of studies using candidate-gene approaches have not produced conclusive results. Large consortium efforts employing genome-wide scanning technology are underway, which hold promise for novel discoveries in renal carcinogenesis.[2]

The genetic basis of kidney cancer: a metabolic disease

Kidney cancer is not a single disease but comprises a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates hypoxia-inducible factor (HIF) levels in the cell. HGF–MET signaling affects the LKB1–AMPK energy sensing cascade. The FLCN–FNIP1–FNIP2 complex binds AMPK and, therefore, might interact with the cellular energy and nutrient sensing pathways AMPK–TSC1/2–mTOR and PI3K–Akt–mTOR. TSC1–TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit. FH and SDH have a central role in the mitochondrial tricarboxylic acid cycle, which is coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy or nutrient sensing, suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease.[3]

Histo-Epidemiology of Kidney Cancer in Cameroon: About 110 Cases

Objectives: To describe the epidemiological and histopathological aspects of kidney cancer in Cameroon.

Materials and Methods: This was a descriptive retrospective study on malignant tumors of the kidney examined in the anatomical pathology laboratories of five regions (Center, Littoral, West, South-west and North-west), over a period of 12 years (2004-2015). The studied parameters were: frequency, age, sex, histological type.

Results: A total of 110 cases of kidney cancer were collected, representing 8.55% of malignant urogenital tumors. The mean age of patients was 28.72±24.79 years (extremes: 4 months – 76 years). Females are relatively more affected than males (56 cases, 50.91%), with female-to-male ratio of 1.04:1. A total of 58 (52.73%) cases of renal cell carcinomas (RCC), 46 (41.82%) cases of nephroblastomas (NB) and 3 (2.73%) of soft tissue tumors were identified.

Conclusion: Kidney cancer is the third urogenital cancer in Cameroon characterized by a relative female predominance with renal cell carcinoma as the predominant histological type.[4]

Diagnosis of Urological Cancer by 1H NMR Based Metabonomics Urinalysis: A Pilot Study

Aims: The most prevalent urological malignancies are prostate cancer (PC), bladder cancer (BC) and renal cancer (RC). The diagnosis of each of these diseases is conducted, in most cases, invasively and each procedure may lead to complications. The method of metabonomic spectrometry by nuclear magnetic resonance of hydrogen (1H NMR) provides pathways of diagnostic information that can identify pathologies without invasive procedures. The possibility of using this method for the diagnosis of those cancers by a single sample of urine has not been described yet.

Study Design: Prospective, observational.

Place and Duration of the Study: Department of Urology and Department Fundamental Chemistry of Universidade Federal de Pernambuco (UFPE), between July of 2015 to February of 2016.

Methodology: A sample of 3 ml of urine was collected from 25 volunteers distributed into 4 groups: A control group (07 volunteers), a PC (08 volunteers), a BC (05 volunteers), and an RC (05 volunteers). All samples underwent 1H MRI to generate spectra.  A multivariate statistics analysis for the development of metabonomic models and comparison analysis groups was performed.

Results: These models showed a slight separation between the control group and each of the three groups of patients with oncological diseases. For the elaboration of the definitive models it was necessary to incorporate the volunteers of the BC and RC into one group (BC/RC). The metabonomic method when compared to control group, shown sensitivity of 90.9%, specificity of 100%, 100% PPV and NPV of 85.7% for CB/CR and sensitivity, specificity, PPV and NPV of 100% for the PC.

Conclusion: This pilot study demonstrates that the method is feasible with easy execution, showing simplicity besides being not invasive and allowing the diagnosis of oncological diseases with a single urine collection.[5]

[1] Vogelzang, N.J. and Stadler, W.M., 1998. Kidney cancer. The Lancet, 352(9141), pp.1691-1696.

[2] Chow, W.H., Dong, L.M. and Devesa, S.S., 2010. Epidemiology and risk factors for kidney cancer. Nature Reviews Urology, 7(5), pp.245-257.

[3] Linehan, W.M., Srinivasan, R. and Schmidt, L.S., 2010. The genetic basis of kidney cancer: a metabolic disease. Nature reviews urology, 7(5), pp.277-285.

[4] Engbang, J.P.N., Sala, B., Fonkwa, C., Ligan, Y., Djimeli, B.D., Simo, G., Moune, A., Fewou, A., Essame, J.L.O., Hasigov, A. and Ephiev, A., 2017. Histo-epidemiology of kidney cancer in Cameroon: about 110 cases. Journal of cancer and tumor international, pp.1-10.

[5] Araújo, L.C.N., Pinto, F.C.M., Costa, T.B.B.C., Silva, R.D., Lima, S.V.C. and Silva, R.O., 2017. Diagnosis of Urological Cancer by 1H NMR Based Metabonomics Urinalysis: A Pilot Study. Journal of Advances in Medicine and Medical Research, pp.1-8.

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