**3. Imaging studies for screening and diagnosing RCC in ESRD**

As mentioned above, ESRD patients are at greatly high risk for developing RCC. In addition, prognosis is better for asymptomatic patients than symptomatic ones among those with ESRDassociated RCC [30]. Since early intervention may prolong cancer free survival [13, 31], periodic imaging studies are considered to be important for detection of RCC in its early stage. Sarasin et al. [32] recommended evaluation strategies with either computed tomography (CT) or US every three years for all patients on dialysis and annually for those with ACDK. To date, screening for RCC is recommended for ESRD patients.

#### **3. 1. Ultrasonography (US)**

imaging (MRI) without the use of contrast material has been reported for the detection of RCC in patients with ACDK [14]. The principle treatment strategy for RCC in dialysis patients is radical nephrectomy (RN). Long-term dialysis patients are at high risk for cardiovascular events [4]. Therefore, less invasive surgery is preferable to avoid postoperative systemic complications. Pathologically, clear and papillary RCC had been considered as common histological types of renal cancer arising from acquired cystic disease (ACD) [15, 16]. Recently, a novel standard pathologic entity of ACD-associated RCC has been established [10, 17-19].

In this chapter, we overview the upated topics on RCCs in ESRD patients, particularly focusing

Patients with ESRD on dialysis have more than 100 times greater risk of RCC than age-matched healthy controls [20-22]. In a series of 831, 804 dialysis patients followed up for an average of 2. 5 years, 2, 053 (0. 25%) patients were diagnosed as having RCC, representing a 3. 6-fold increased risk over the general population [23]. Kojima et al. reported that in a cohort of 2, 624 patients 81. 8% developed ACDK during a median dialysis time of 11 years and that 1. 68% developed RCC [24]. The risk is considered to be progressively higher in patients with a longer duration of dialysis. According to some recent publications, a long duration of dialysis (> 10y) has a stronger association with ACD-associated RCC than other subtypes of RCC [25-27]. In a multicenter retrospective study by Neuzillet et al. , RCC developing in patients with ESRD has many favorable clinical, pathologic, and outcome features compared with RCC in patients

According to a multicenter retrospective study, more patients diagnosed as having RCC are young and asymptomatic in the ESRD group than the non-ESRD counterpart [28]. Denton et al. reported that of 260 patients who underwent ipsilateral native nephrectomy at the time of transplantation, 11 (4. 2%) diagnosed as RCC with short duration of hemodialysis, and age was significant risk factor of RCC [11]. In ESRD patients, modality of dialysis does not appear to associate with the incidence of RCC; the incidence of RCC is almost same in patients on hemodialysis and those on peritoneal dialysis. Savaji et al. reported the annual incidence of

As mentioned above, ESRD patients are at greatly high risk for developing RCC. In addition, prognosis is better for asymptomatic patients than symptomatic ones among those with ESRDassociated RCC [30]. Since early intervention may prolong cancer free survival [13, 31], periodic imaging studies are considered to be important for detection of RCC in its early stage. Sarasin et al. [32] recommended evaluation strategies with either computed tomography (CT) or US

RCC was estimated to be 130 per 100, 000 patients on peritoneal dialysis [29].

**3. Imaging studies for screening and diagnosing RCC in ESRD**

on screening and diagnosis, minimally invasive surgery, and pathology.

**2. Epidemiology of RCC in hemodialysis patients**

without ESRD.

144 Updates in Hemodialysis

Past studies evaluating the prevalence of RCC in patients with ACDK were based on US diagnosis. US is the most widely used screening tool for RCC in patients with ESRD. On USbased screening, RCC was identified in native kidneys in 3. 8% and 3. 9% of ESRD patients of pre- and post-transplantation, respectively [33, 34], which represents a 100-fold increase in prevalence compared to the general population. Gulanikar et al. [33] reported that sensitivity of US screening for the diagnosis of RCC was 36. 3% in ESRD patients.

Because ESRD kidney shows heterogeneous and hyperechoic parenchymal echo-texture and irregular parenchymal contour associated with uneven parenchymal atrophy and compensa‐ tory hypertrophy, it would be more difficult to detect RCC on US in ESRD kidneys than in non-ESRD kidneys. Compensatory hypertrophy sometimes produces a mass effect or compresses the pelvo-calyceal systems and thus closely mimics renal neoplasm [35]. US has disadvantage of operator-dependence and often fails to distinguish RCC from hemorrhagic cyst [13].

Among several diagnostic parameters of US, Kim et al. reported the possibility of usefulness of resistive index (RI), which is calculated as (peak systolic velocity – end-diastolic velocity) / peak-systolic velocity on renal Doppler sonography, in detection of RCC in ESRD kidneys. RCC arising in ESRD kidneys shows significantly lower RI values than the background renal parenchyma [36]. Speculated theoretical background is as follows; because tumor vessels generally lack smooth muscle layer, diastolic flow of the tumor vessels is higher than that of the normal vessels, resulting in lower RI values in tumor tissues compared to the nonneoplastic counterparts.

### **3. 2. Computed Tomography (CT)**

Contrast-enhanced computed tomography (CECT) is the most widely used modality for the detection of RCC associated with ACDK (Fig. 1). Takebayashi et al. [37] demonstrated that early enhanced helical CT could detect RCC better than delayed enhanced CT in ESRD patients with and without ACDK because the cortex of the ESRD kidneys shows minimal enhancement in the early phase, rendering higher differences in the attenuation values between the RCC and the atrophic parenchyma. However, as ESRD patients require life-long follow-up, screening with CECT may be burdensome in that it uses ionizing radiation and poses a risk for contrast-induced nephropathy.

#### *3. 2. 1. Bosniak renal cyst classification system*

Schwarz et al. [38] recommended a CT-based screening and management protocol in trans‐ plantrecipients, incorporating the BosniakRenal Cyst Classification System. The Bosniak renal cyst classification system was initially reported in 1986 based on CT scan findings [39]. The Bosniak system consists of four categories, ranging from simple to complex cysts. Fortytwo-59%ofcategoryIIIand90-100%ofcategoryIVlesionswereproventobemalignancy[40-42]. Figure 1

**Figure 1.** CT images of a 65-year-old man with ACD-associated RCC. a: Unenhancement CT shows multiple small cysts and a mass (arrow). b: At early enhancement phase, the mass (arrow) is slightly and heterogenously enhanced.

Category I. —Simple benign cysts showing homogeneous water content, and a sharp interface with adjacent renal parenchyma, without wall thickening, calcification, or enhancement.

Category II. — Cystic lesions with one or two thin (≤1 mm thick) septations or thin, fine calcification in their walls or septa and hyperdense benign cysts with all the features of category I cysts except for homogeneously high attenuation. A benign category II lesion must be 3 cm or less in diameter and have one quarter of its wall extending outside the kidney, without contrast enhancement.

Category IIF. — Minimally complicated cysts that need follow-up. This group is not well defined by Bosniak originally and consists of lesions that are not classified into category II. There are some suspicious features that deserve follow-up.

Category III. — True indeterminate cystic masses that need surgical evaluation but prove to be benign in many cases. They may show uniform wall thickening, a multilocular nature with multiple enhancing septa, thick or irregular peripheral calcification. Hyperdense lesions that do not fall into category II are classified in this group.

Category IV. —Lesions with uneven or contrast-enhanced thick wall, contrast-enhanced or large nodules in the wall, or clearly solid components in the cystic lesion.

#### **3. 3. Magnetic Resonance Imaging (MRI)**

Recently, MRI is one of topics in diagnosis of ESRD-related RCC. Some studies have reported the usefulness of diffusion-weighted MRI in differentiating RCC from benign cyst, without the use of contrast material [43-46]. Diffusion-weighted imaging (DWI) is a noninvasive functional modality using strong bipolar gradients to create a sensitivity of the signal to the thermally-induced Brownian motion of water molecules and in vivo measure‐ ment of molecular diffusion [47]. This imaging technique has been applied to the diagno‐ sis of cancer [48]. The apparent diffusion coefficient (ADC) is a quantitative parameter of the degree of diffusion, which is calculated from several DWI images of different *b* values. RCC showed a tendency toward higher signal intensities (SIs) with lower ADC values on DWI obtained at high *b* values than benign cysts (Fig. 2). Akita et al. [14] reported 10 RCCs containing viable parts in the pathologic specimens showed high signal areas on DWI (at high *b* values). Solitary RCC with no macroscopic degeneration was visualized as a homogenous high SI on DWI and as a homogenous iso SI on T2-weighted image (T2WI). They also reported that the mean ADC of ACD-associated RCCs was lower than the value of clear cell RCCs. Several researchers reported T1-weighted image (T1WI) is useful for discriminating between RCC and hemorrhagic cyst. Hemorrhagic cyst shows homogene‐ ous high SIs or fluid-iron levels on T1WI [13, 49]. Figure 2

**Figure 2.** MRI images of a 71-year-old man with ACD-associated RCC. a: Axial T2WI shows a heterogenous signal in‐ tensity mass (arrow). b: DWI shows heterogenous high signal intensity mass (arrow). c:ADC map demonstrates the tumor (arrow) with ADC value of 1. 00 ×10-3 mm2 /s.
