Which of the following is NOT a recognised risk factor for the development of renal carcinoma?
Answer B
Hypertension and the use of anti-hypertensive medications are associated with an increased risk of RCC. Studies have shown a clear dose-response relationship between elevated blood pressure and an increased risk of RCC. The independent contributions of hypertension and the use of antihypertensive medications have been difficult to separate, as most studies are based on a diagnosis of hypertension which is inevitably associated with treatment with antihypertensive drugs. Better control of blood pressure may lower RCC risk.
Whilst diabetes mellitus (DM) type 2 has been shown to be associated with an increased risk of several cancers, no significant increased risk has been demonstrated between DM and RCC [1]. Obesity has been established as a risk factor for RCC in a number of studies. A meta-analysis [2], demonstrated that the risk of RCC increased with elevated body mass index (BMI), with summary risk estimates (per 5 kg/m2 increase in BMI) of 1.24 in men and 1.34 in women. It has been proposed that the increased risk of RCC in obese patients may be due to increased exposure to oestrogens and androgens.
Cigarette smoking is a well-established risk factor for RCC. A meta-analysis of 24 studies showed that a history of smoking increases the risk of RCC compared to never smoking. Though the association between smoking and RCC is relatively weak, a dose-response relationship has been shown. Acquired renal cystic disease (ARCD) arises predominantly in patients with end-stage renal disease treated with haemodialysis. The incidence of RCC in ARCD is up to six times higher than in the general population. The risk of developing RCC does not appear to decrease after renal transplantation.
A 67-year-old man is noted to have an incidental small renal mass in his left kidney whilst undergoing investigation for rectal bleeding. An upper pole tumour is noted to be entirely endophytic and 38 mm in maximal dimension. The tumour lies anteriorly within the upper pole and is in contact with the collecting system though does not cross the inter-polar lines. What would be the R.E.N.A.L. nephrometry score of this tumour?
The R.E.N.A.L nephrometry scoring system was introduced by Kutikov et al. [3] as a standardised scoring system to characterise renal tumour anatomy and complexity in a reproducible, quantifiable manner. The aim of the scoring system was to allow meaningful comparisons of renal masses in clinical practice and in the urological literature. Tumours are evaluated using a 3-point scale on the basis of the following:
The above tumours would be scored as; R = 1, E = 3, N = 3, a, L = 1, giving a nephrometry score of 8a.
R.E.N.A.L nephrometry scores have been used to develop a nomogram that helps to predict the likelihood of malignant and high-grade pathology of an enhancing renal mass. Increasing tumour complexity as determined by nephrometry score is associated with an increased likelihood of major complications. Two alternative scoring systems have also been developed (PADUA and C-index) with the intention of providing a standardised descriptive system for renal masses based on radiologic findings.
Von Hippel–Lindau disease is associated with mutations on which gene locus?
Answer B Von Hippel–Lindau (VHL) disease is the most common hereditary renal cancer syndrome with an incidence of 1 in 35,000 live births. VHL disease arises as a result of mutations in the Von Hippel–Lindau tumour suppressor (VHL) gene located at 3p25. Germ line mutations are present in nearly 100% of affected individuals with subsequent inactivation of the wild-type copy of the VHL gene leading to the clinical manifestation of VHL disease; clear cell renal cell carcinoma, CNS or retinal haemangioblastoma, pheochromocytoma and pancreatic cysts. RCCs are seen in up to 50% of VHL patients are often multiple and bilateral. Metastatic RCC is the most common cause of mortality in VHL patients.
The VHL protein acts as an E3 ubiquitin ligase and targets the alpha sub-unit of hypoxia inducible factor (HIF) for ubiquitin-mediated degradation. The inactivating mutations of both alleles of the VHL gene seen in VHL disease results in the constitutive over expression of HIF and its downstream targets VEGF, PDGF, TGF-a, erythropoietin, GLUT-1 and CA9, which in turn are key drivers of the oncogenic.
The fumarate hydratase gene is located at locus 1q42 and is associated with hereditary leiomyomatosis and RCC. 7q31 represents the locus for the c-met oncogene linked to hereditary papillary RCC. Tuberose sclerosis has been shown to arise as a result of mutations in the hamartin gene located at 9q34, whilst 17p11 is the locus for the folliculin gene which results in Birt– Hogg–Dubé syndrome.
Which one of the following statements regarding active surveillance of T1a small renal masses is CORRECT?
Answer C
Active surveillance has traditionally been reserved for the treatment of T1 small renal masses in elderly patients with multiple co-morbidities or those who decline surgery. The current guidelines for the treatment of T1 renal cancer from the American Urological Association (AUA) and the European Association of Urology (EAU) both propose partial nephrectomy as the gold standard treatment option in the surgically fit patient.
A number of studies have shown that on average benign oncocytomas grow at the same rate as RCC.
Metastatic progression rates for T1a SRMs managed with AS are reported to be between 1% and 2%. Kunkle et al performed a meta-analysis of oncologic outcomes for over 6,000 SRMs and concluded that no statistically significant differences were detected in the incidence of metastatic progression regardless of whether lesions were excised, ablated or observed [6]. A meta-analysis of active surveillance for SRMs revealed a mean growth rate of 0.28 cm/year at a mean follow up of 34 months. Data from a pooled analysis by Smaldone et al demonstrated that T1a tumours have a growth rate of 0.31 cm/year [7]. Jewett et al. noted an annual growth rate of 0.13 cm/year for T1a masses in the prospective Canadian Small Renal Mass Trial.
Numerous studies have previously demonstrated a degree of variability in growth rates of T1 renal masses. Studies have demonstrated that 23%–36% of T1 SRMs have zero or negative growth rates. The pooled analysis of 880 patients with SRMs by Smaldone et al observed that metastatic progression was not observed in any patient who had negative or zero growth on follow-up, which is of great importance when counselling patients being managed with AS.
Which one of the following statements regarding locally advanced renal cell cancer is CORRECT?
The TNM 2017 staging classifies T3b as tumour grossly extending into the inferior vena cava below the diaphragm. The 5-year cancer-specific survival rates for T3b renal cell cancer is 40%. The ipsilateral adrenal gland should be removed when there is evidence on CT imaging of direct invasion of the adrenal gland by the renal cell cancer or a metastasis is present in the adrenal gland that appears solitary. Tumour thrombus invading the IVC wall portends a worse prognosis (T3c staging in 2017 classification) than tumour thrombus in the IVC lumen below the diaphragm (T3b staging in 2010 classification). Radical Excision of regional para-aortic lymph nodes has not been shown to significantly improve cancer specific survival.
Click to expand