|Ahead of print publication
Differentiating renal pelvic cancer from renal cell carcinoma with 18-fluorodeoxyglucose positron emission tomography-computed tomography
Murat Dursun1, Emin Ozbek2, Alper Otunctemur3, Huseyin Besiroglu3
1 Department of Urology, Bahcelievler State Hospital, Istanbul, Turkey
2 Department of Urology, Istanbul Training and Research Hospital, Istanbul, Turkey
3 Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
Department of Urology, Bahcelievler State Hospital, 34180, Kocasinan Merkez, Bahcelievler, Istanbul
Source of Support: None, Conflict of Interest: None
Background: The differential diagnosis of pelvis renalis cancer (PRC) from renal cell cancer (RCC) is difficult. Because of that, in this study, we compared the standardized uptake value (SUV) with positron emission tomography-computed tomography (PET-CT) of the RCC and PRC.
Methods: Twenty-one patients (12 males, 9 females; age range: 33–74 years; mean age ± standard deviation [SD]: 57.14 ± 17.6) with suspected primary renal cell cancer as Group 1 and 8 patients (6 male, 2 female; age range, 61–81; mean age ± SD, 71.5 ± 5.65) with suspected renal pelvis cancer as Group 2 detected by conventional imaging techniques (CT, magnetic resonance [MR] imaging, ultrasound, intravenous urogram, CT urography, MR urography) underwent fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT imaging between August 2010 and October 2012.
Results: Mean age is 57.14 (33–74) years in Group 1 and 71.5 (61–81) years in Group 2, respectively. The mean maximum SUV (SUVmax) value was 4.6 ± 2.1 in RCC group and 16.6 ± 6.9 in PRC group. At the 18-FDG PET/CT scanning, SUVmax value higher in patients with PRC than in the patients with RCC. It was statistically different (P < 0.001).
Conclusion: We suggested that PET/CT can be used for the differential diagnosis of renal pelvis tumor and RCC. However, further studies with larger patient number are needed to confirm our suggestion. To clarify the mechanisms of underlying these differences, molecular advanced molecular studies are needed.
Keywords: 18-fluorodeoxyglucose positron emission tomography, renal cell carcinoma, maximum standardized uptake value
|How to cite this URL:|
Dursun M, Ozbek E, Otunctemur A, Besiroglu H. Differentiating renal pelvic cancer from renal cell carcinoma with 18-fluorodeoxyglucose positron emission tomography-computed tomography. J Can Res Ther [Epub ahead of print] [cited 2020 Sep 18]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=257456
| > Introduction|| |
Kidney cancer among adults includes malignant tumors arising from the renal parenchyma and renal pelvis. Renal parenchyma cancer is the predominant kidney cancer, mainly of the adenocarcinoma cell type (renal cell cancer). Renal cell cancer (RCC) accounts for 3% of all adult cancers and 90%–95% of neoplasms of the kidney. It is a highly heterogeneous disease with many distinct histologic subtypes., Clear cell RCC, arising from the proximal tubular epithelial cells, is the most common sporadic subtype constituting 70%–80% of RCC, followed by papillary (10%–15%) and chromophobe (5%) RCC. As we know, renal cell cancer incidence rates increased. The increase can be partly explained by improved detection by the use of ultrasound (US) and computed tomography (CT), but it may also be due to an increasing prevalence of risk factors., Established lifestyle-related risk factors for RCC are obesity, hypertension, and smoking, and these risk factors have been estimated to account for up to 50% of the cases.,
Compared to renal cell cancer, incidence rates for renal pelvis cancer are much lower. Renal pelvis cancers are mostly of the transitional cell type. Urothelial cancers of the renal pelvis and collecting system constitute approximately 10%–15% of all renal tumors: 90% are transitional cell carcinoma (TCC), 9% are squamous cell carcinoma, and 1% are mucinous adenocarcinoma., Patients usually present with gross or microscopic hematuria, dull flank pain, or acute renal colic due to obstruction. Synchronous bladder cancer occurs in 2%–4% of patients with upper tract tumors; this is the reason for a full urothelial screening. The diagnosis of upper urinary tract (UUT) urothelial carcinomas (UTUCs) is difficult. Historically, the presence of a filling defect on ureteropyelography and a positive cytology result established the diagnosis. The development of both better imaging techniques, including computed tomography urogram or magnetic resonance urogram, and endoscopic instruments, such as flexible and digital ureteroscopes, improved the ability to identify and characterize malignancies., Ureteroscopic evaluation with biopsy is currently the gold standard for both visualizing and diagnosing UTUCs. However, this technique is invasive, and we need an imaging method for the diagnosis of UUT urothelial cancer. Although CT urography is actually the gold standard imaging of UTUCs, magnetic resonance imaging (MRI) is becoming increasingly used for the study of renal and UUT tumors. In the literature, we did not see any information about the positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (18F-FDG) to determine the renal pelvis cancer, but we think that 18F-FDG may be important imaging modality. According to this, we evaluated the patients who have renal parenchyma and renal pelvis cancer. We performed 18F-FDG PET/CT for imaging preoperatively. We compared the standardized uptake value (SUV) of the renal cell and renal pelvis cancer.
| > Methods|| |
Twenty-one patients (12 males, 9 females; age range: 33–74 years; mean age ± standard deviation [SD]: 57.14 ± 17.6) with suspected primary renal cell cancer as Group 1 and 8 patients (6 males, 2 females; age range: 61–81; mean age ± SD: 71.5 ± 5.65) with suspected renal pelvis cancer as Group 2 detected by conventional imaging techniques (CT, MRI, US, intravenous urogram, CT urography, and magnetic resonance urography) underwent 18F-FDG PET/CT imaging between August 2010 and October 2012. The patients were divided into two groups as previous imaging.
Diabetic patients were excluded from the study. Furthermore, the patients who had lymph node metastases and distant metastases with diagnosis by imaging previously were excluded from the study. All patients underwent nephrectomy, nephroureterectomy, or surgical resection of the renal lesions, and final diagnoses were based on histopathology. The study was approved by the Ethical Committee of Okmeydani Training and Research Hospital.
PET/CT studies were carried out using an integrated PET/CT scanner, which consisted of a full-ring HI-REZ LSO PET and a six-slice CT (Siemens Biograph 6; Siemens, Chicago, Illinois, USA). Patients were instructed to fast for at least 6 h before 18F-FDG injection. Blood glucose levels were measured before the study, and 18F-FDG injections were administered only when the blood glucose levels were below 140 mg/dl. The patients were injected with 18F-FDG (370–555 MBq) according to body weight. The initial whole-body imaging commenced 55 ± 5 min after injection of 18F–FDG, and patients received diuretics (furosemide, 10 mg intravenously [iv]) 30 min before imaging in an attempt to limit physiological activity from the renal collecting system. The patients were instructed to void before imaging. According to our nuclear medicine department protocol, they did not use iv contrast agent in routine practice. The CT portion of the study was carried out without an intravenous contrast medium, just for defining anatomical landmarks and making attenuation correction on PET images. CT was acquired first with the following parameters: 50 mAs, 140 kV, and 5-mm section thickness. Whole-body CT was performed in a craniocaudal direction. PET images were acquired in a three-dimensional mode, from the base of the skull to the mid-thigh, with five-to-seven bed positions of 3 min each, and PET data were collected in a caudocranial direction. The CT data were matched and fused with the PET data.
All 18-FDG PET/CT scans were interpreted by an experienced radiologist in conjunction with an experienced nuclear medicine physician who was both aware of the suspicion of renal lesions with the imaging findings of the patients. Two physicians had access to other imaging studies which were determined before contrast-enhanced CT or MRI. The 18-FDG PET portion and the CT portion of PET/CT were jointly interpreted using a dedicated image fusion workstation. SUVs were obtained after drawing a region of interest with a diameter of 1 cm on the consequent four-to-eight PET scan slices at the site of the renal lesions. The slice with a maximal FDG uptake in the region of interest was chosen for measurements of maximum SUV (SUVmax). The SUVmax was calculated using the following formula: SUV = cdc/(d/w), where cdc is the decay-corrected tracer tissue concentration (in Bq/g); d, the injected dose (in Bq); and w, the patient's body weight (in g).
For the comparison of the SUVs from the tumors, the Mann–Whitney U-test was used, and P < 0.05 was considered to indicate a statistically significant difference.
| > Results|| |
Mean age is 57.14 (33–74) and 71.5 (61–81) years, in Group 1 and 2, respectively. The patients in Group 2 were older than patients in Group 1. Twelve patients were male and 9 patients were female in Group 1 and also 6 males and 2 females in Group 2. Fifteen (71%) patients had clear cell, 4 (19%) patients had papillary, and 2 (10%) patients had chromophobe RCC in Group 1. Furthermore, there was no significant difference between SUVmax values of the RCC subgroups. The mean SUVmax value was 4.6 ± 2.1 in RCC group and 16.6 ± 6.9 in renal pelvis tumor group. The median SUVmax value was 3.98 ± 1.9 in Group 1 and 14.2 ± 5.8 in Group 2. At the 18-FDG PET/CT scanning, SUVmax value was higher in patients with pelvis renalis cancer (PRC) than in the patients with renal RCC. It was statistically different (P < 0.001). On the other hand, we found no statistical difference between tumor size. However, mean tumor size was higher in Group 2 (5.55 ± 2.41 in RCC group and 6.93 ± 3.19 in PRC group). PET/CT imaging was shown in [Figure 1] and [Figure 2] in patients with renal pelvis tumor and RCC, respectively. All patients' previously diagnosis confirmed with histopathologic result after surgery.
|Figure 1: Axial slices of the positron emission tomography and computed tomography components of the fluorodeoxyglucose positron emission tomography and computed tomography scan (patient no: 23) showing a renal pelvis tumor with intense abnormal fluorodeoxyglucose uptake (maximum standardized uptake value: 12.7)|
Click here to view
|Figure 2: Axial slices of positron emission tomography and computed tomography images of the fluorodeoxyglucose positron emission tomography and computed tomography scan showing relatively low abnormal fluorodeoxyglucose uptake in a patient with RCC (maximum standardized uptake value: 4.2)|
Click here to view
| > Discussion|| |
Increased rates of respiration, glucose uptake, and glucose metabolism in malignant tumors have been documented since the early observations by Warenburg that are among the most characteristic biochemical markers of the transformed phenotype. With the availability of sensitive PET scanners and 2-FDG for measuring regional tissue glucose metabolism, enhanced tumoral glucose consumption has gained considerable clinical interest, forming one important pathophysiological mechanism for detecting and staging a multitude of human malignant tumors and controlling cytoreductive therapy for them by PET., As a result of these developments, PET-CT has been used in the diagnosis and follow-up of renal cell cancer. Only a few studies have applied FDG-PET to renal cell carcinoma. Miyauchi et al. and Hoh et al. demonstrated that FDG-PET was not useful for diagnosing all cases of renal cell carcinoma. However, Bachor et al. evaluated 29 patients with solid renal masses. FDG-PET had a sensitivity of 77% (20/26) in histologically confirmed cases of RCC, with three false-positive results. Furthermore, Kang et al. found that on the clinical use of PET in the detection of RCC, FDG PET exhibited a sensitivity of 60% and specificity of 100% for primary RCC. Although the increasing specificity rate for RCC, there is no information about using for renal pelvis tumor. Hence, in this study, we evaluated the applicability of PET/CT scanning for renal pelvis tumor and the role for differential diagnosis in RCC and renal pelvis tumor. Moreover, we have seen that SUVmax value was higher in the patients with renal pelvis tumor. Although no information in the literature about using PET/CT for UTUCs, there were some reports about the using PET/CT for bladder urothelial cancer. In this context, we thought that PET/CT may be a useful diagnostic method for UTUCs and evaluated the diagnostic value of PET/CT for UTUCs.
Multidetector computed tomographic urography (MDCTU) is the gold standard for exploration of the UUT and has replaced intravenous excretory urography., The detection rate of UTUCs is satisfactory for this type of imaging: 96% sensitivity and 99% specificity for polypoid lesions between 5 and 10 mm. MRI urography is indicated in patients who cannot be subjected to an MDCTU. The detection rate of MRI is 75% after contrast injection for tumors <2 cm. More invasive methods such as ureteroscopy is a better approach to diagnose UUT-urothelial cell carcinomas., A flexible ureteroscope can explore the ureter macroscopically and reach renal cavities in 95% of cases, and it can assess the aspect of the tumor, obtain tumor biopsy, and determine tumor grade in 90% of cases with a low false-negative rate. In this study, we found higher SUVmax values with 18-FDG PET/CT in patients with renal pelvis tumor. Moreover, we suggested that PET/CT may use the differential diagnosis of UTUCs.
In literature, there is no study explaining the mechanism of high SUVmax value of renal pelvis cancer in 18-FDG PET/CT than that of in renal cell carcinoma. This can be explained by higher uptake of 18-FDG by renal pelvic TCC than renal cell carcinoma. Classically, it is well known that renal cell carcinoma originates from proximal renal tubular epithelial cell, whereas renal pelvis cancers from urinary transitional cell epithelial cells.
Differences in the metabolic activities of PRC and RCC cells may explain the difference in SUVmax values. 18-FDG transported into cells with different types of glucose transporter proteins (GLUTs). GLUT1 expression in RCC and urothelial cancer of the bladder has been reported in previous studies. Despite the increased expression of hypoxia-inducible factor-1 (HIF-1) in RCC, in TCC, the role of HIF-1 is not so important. Different expression of HIF-1 in RCC and TCCs may explain this difference in SUVmax values.,,
We think that there are differences in GLUT expressions in renal pelvic cancers and RCC. Another possible molecular mechanism explaining these differences is overexpression of p-glycoprotein (p-GP), encoded by multidrug resistance 1 gene and p-GP in RCC. p-GP is an energy-dependent efflux pump, which is present in RCC cells and pump drugs and contrast substances outside of the cells. Similarly, 18-FDG may be released outside of the cancer cells, and as a result of this in 18-FDG PET/CT imagine, SUVmax values may be found low in RCC than TCC of the renal pelvis. Further molecular studies are needed to confirm our suggestions.
The number of patients with PRC is only 8 and this is seen as one of the limitations of our study. Also, lack of reliable anatomic landmarks due to plain CT with low dose is the other limitation. Other limitation of our study is that RCC is a heterogeneous disease by itself as far as the SUVmax is concerned. In a previous study, Nakaigawa et al reported that SUVmax may range from undetectable to very high in renal cell cancer disease. In our study, the patients with PRC are delayed for diagnosis. Because of that, the tumor sizes are large in this group. As we know, the detection rate of UTUCs is satisfactory for this type of imaging: 96% sensitivity and 99% specificity for polypoid lesions between 5 and 10 mm. But, PET-CT can be useful in differentiating patients with small tumors in kidney.
| > Conclusion|| |
Our findings suggest that FDG PET/CT can be used for differentiating renal pelvis tumour and RCC. However, this is a preliminary study and studies with larger patient numbers are needed to validate our findings with further molecular studies to clarify the mechanisms underlying these differences.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer. Nat Rev Urol 2010;7:245-57.
Eble J, Sauter G, Epstein J, Sesterhenn I. Pathology and genetics. Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press; 2001.
Lopez-Beltran A, Scarpelli M, Montironi R, Kirkali Z. 2004 WHO classification of the renal tumors of the adults. Eur Urol 2006;49:798-805.
Curti BD. Renal cell carcinoma. JAMA 2004;292:97-100.
Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr. Rising incidence of renal cell cancer in the United States. JAMA 1999;281:1628-31.
Weikert S, Ljungberg B. Contemporary epidemiology of renal cell carcinoma: Perspectives of primary prevention. World J Urol 2010;28:247-52.
Benichou J, Chow WH, McLaughlin JK, Mandel JS, Fraumeni JF Jr. Population attributable risk of renal cell cancer in minnesota. Am J Epidemiol 1998;148:424-30.
Guinan P, Vogelzang NJ, Randazzo R, Sener S, Chmiel J, Fremgen A, et al.
Renal pelvic cancer: A review of 611 patients treated in Illinois 1975-1985. Cancer incidence and end results committee. Urology 1992;40:393-9.
Bree RL, Schultz SR, Hayes R. Large infiltrating renal transitional cell carcinomas: CT and ultrasound features. J Comput Assist Tomogr 1990;14:381-5.
Vikram R, Sandler CM, Ng CS. Imaging and staging of transitional cell carcinoma: Part 2, upper urinary tract. AJR Am J Roentgenol 2009;192:1488-93.
Kirkali Z, Tuzel E. Transitional cell carcinoma of the ureter and renal pelvis. Crit Rev Oncol Hematol 2003;47:155-69.
Vashistha V, Shabsigh A, Zynger DL. Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma. Arch Pathol Lab Med 2013;137:400-7.
Sufana Iancu A, Colin P, Puech P, Villers A, Ouzzane A, Fantoni JC, et al.
Significance of ADC value for detection and characterization of urothelial carcinoma of upper urinary tract using diffusion-weighted MRI. World J Urol 2013;31:13-9.
Warenburg O. The Metabolism of Tumors. New York: Richard R. Smith Inc.; 1931.
Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991;32:623-48.
Wahl RL. Positron emission tomography: Applications in oncology. In: Murray IC, Ell PJ, editors. Nuclear Medicine in Clinical Diagnosis and Treatment. Vol. 2. Edinburgh: Churchill Livingstone; 1994. p. 801-20.
Miyauchi T, Brown RS, Grossman HB, Wojno K, Wahl RL. Correlation between visualization of primary renal cancer by FDG-PET and histopathological findings. J Nucl Med 1996;37 (Suppl):64.
Hoh CK, Figlin RA, Bdildegron A. Evaluation of renal cell carcinoma with whole body FDG-PET [abstract]. J Nucl Med l996:37:l4IP.
Bachor R, Kotzerke J, Gottfried HW, Brändle E, Reske SN, Hautmann R, et al.
Positron emission tomography in diagnosis of renal cell carcinoma. Urologe A 1996;35:146-50.
Kang DE, White RL Jr., Zuger JH, Sasser HC, Teigland CM. Clinical use of fluorodeoxyglucose F 18 positron emission tomography for detection of renal cell carcinoma. J Urol 2004;171:1806-9.
Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, et al.
EAU guidelines on renal cell carcinoma: The 2010 update. Eur Urol 2010;58:398-406.
Dillman JR, Caoili EM, Cohan RH, Ellis JH, Francis IR, Schipper MJ, et al.
Detection of upper tract urothelial neoplasms: Sensitivity of axial, coronal reformatted, and curved-planar reformatted image-types utilizing 16-row multi-detector CT urography. Abdom Imaging 2008;33:707-16.
Wang LJ, Wong YC, Chuang CK, Huang CC, Pang ST. Diagnostic accuracy of transitional cell carcinoma on multidetector computerized tomography urography in patients with gross hematuria. J Urol 2009;181:524-31.
Takahashi N, Glockner JF, Hartman RP, King BF, Leibovich BC, Stanley DW, et al.
Gadolinium enhanced magnetic resonance urography for upper urinary tract malignancy. J Urol 2010;183:1330-65.
Takahashi N, Kawashima A, Glockner JF, Hartman RP, Leibovich BC, Brau AC, et al.
Small (<2-cm) upper-tract urothelial carcinoma: Evaluation with gadolinium-enhanced three-dimensional spoiled gradient-recalled echo MR urography. Radiology 2008;247:451-7.
Lee KS, Zeikus E, DeWolf WC, Rofsky NM, Pedrosa I. MR urography versus retrograde pyelography/ureteroscopy for the exclusion of upper urinary tract malignancy. Clin Radiol 2010;65:185-92.
Ishikawa S, Abe T, Shinohara N, Harabayashi T, Sazawa A, Maruyama S, et al.
Impact of diagnostic ureteroscopy on intravesical recurrence and survival in patients with urothelial carcinoma of the upper urinary tract. J Urol 2010;184:883-7.
Tavora F, Fajardo DA, Lee TK, Lotan T, Miller JS, Miyamoto H, et al.
Small endoscopic biopsies of the ureter and renal pelvis: Pathologic pitfalls. Am J Surg Pathol 2009;33:1540-6.
Gupta R, Paner GP, Amin MB. Neoplasms of the upper urinary tract: A review with focus on urothelial carcinoma of the pelvicalyceal system and aspects related to its diagnosis and reporting. Adv Anat Pathol 2008;15:127-39.
Younes M, Juarez D, Lechago LV, Lerner SP. Glut 1 expression in transitional cell carcinoma of the urinary bladder is associated with poor patient survival. Anticancer Res 2001;21:575-8.
Zhou JT, Cai ZM, Li NC, Na YQ. Expression of hypoxia inducible factor-1alpha and glucose transporter protein 1 in renal and bladder cancers and the clinical significance thereof. Zhonghua Yi Xue Za Zhi 2006;86:1970-4.
Hao YX, He ZW, Zhu JH, Shen Q, Sun JZ, DU N, et al.
Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene. Chin Med J (Engl) 2012;125:2741-5.
Nakaigawa N, Kondo K, Tateishi U, Minamimoto R, Kaneta T, Namura K, et al.
FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: Max SUVmax predicts survival of patients with advanced renal cell carcinoma. BMC Cancer 2016;16:67.
[Figure 1], [Figure 2]