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Diagnosis and Management of a De Novo Urothelial Carcinoma in a Kidney Allograft: A Case Report
Diagnosis and Management of a De Novo Urothelial Carcinoma in a Kidney Allograft: A Case Report } , Gergely Kiss, Ádám Z. Farkas*, Szilárd Török, János Balázs Kovács, László Piros, Gyula Végso Dávid Korda, András Bibok, Erika Hartmann, Ákos P. Deák, and Attila Doros Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
ABSTRACT Introduction. Following renal transplantation, the incidence of malignancies is 3e5 times higher than that of healthy individuals. Among other type of cancers, the risk of urological tumors is also elevated. However, only a few cases of de novo transitional cell carcinomas occurring in renal allografts have been reported. Case report. A 63-year-old tertiary transplanted male patient was urgently hospitalized for a painless macroscopic hematuria. Ultrasonography revealed pyelectasis and a hematoma in the renal pelvis. A percutaneous nephrostomy tube was inserted. An anterograde pyelography was performed later, where a filling defect was still observable in the location of the previously reported hypoechoic mass. Contrast-enhanced ultrasonography showed enhancement of the lesion. An ultrasound-guided percutaneous biopsy was performed. The histologic evaluation revealed a high-grade transitional cell carcinoma. A whole-body staging computed tomography scan did not show signs of metastatic disease. The renal allograft was surgically removed. No disease progression was observed during the 21-month follow-up period. Conclusions. Painless hematuria and asymptomatic hydronephrosis occurring after kidney transplantation should raise the possibility of urothelial carcinoma in the kidney graft. Contrast-enhanced ultrasound should be considered as a first-line diagnostic modality because it is easily accessible and does not raise concerns about nephrotoxicity or radiation burden.
T
HE OVERALL incidence of malignancies had been reported to be 3e5 times higher in renal transplant recipients compared to the general population [1]. The main reason for this higher incidence is the permanent immunosuppressive therapy required, especially when induction is administered at the time of transplantation [2]. The most frequent types of malignancies are lymphoproliferative disorders and skin cancers [3e6], followed by urological tumors [7e9]. The majority of de novo urological tumors are renal cell carcinomas arising from the patients’ native kidneys [10]; however, an increased risk of urothelial cancers has also been reported [11]. In this article we report a de novo transitional cell carcinoma (TCC) in a kidney graft, which has an extremely low prevalence and only a few cases have been reported previously [12e14]. ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 1281e1285 (2019)
CASE REPORT Almost 9 years after undergoing a cadaveric kidney transplantation (KT), a tertiary transplanted patient was urgently hospitalized in our department for a painless macroscopic hematuria and elevated serum creatinine level. His medical history consisted of an IgAnephropathy discovered at the age of 18 years. He received his first cadaveric KT in 1986. This kidney graft was removed following a month-long febrile state due to a severe cytomegalovirus
*Address correspondence to Ádám Z. Farkas, Semmelweis University, Department of Transplantation and Surgery, 1082 Budapest, Baross utca 23-25, Hungary. Tel: þ36 1 2676000; Fax: þ36 1 3172166. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.04.011
1281
1282 infection. His second cadaveric transplantation was performed in 1990 in Vienna. The patient had chronic allograft injury and underwent a graftectomy 12 years later. He was driven back to regular kidney replacement therapy; however, preparations for a further KT were already decided and carried out in accordance with the patient’s wishes. He received a third cadaveric graft in 2008 (1 HLA-A, 1 HLA-B, 1 HLA-DR antigen match), followed by daclizumab induction therapy. The patient received tacrolimus (4.5 mg), mycophenolic acid (2 500 mg) and prednisolone (5 mg) as maintenance immunosuppression. Following his admittance in 2017, a Doppler ultrasonography of the kidney graft was performed that revealed pyelectasis and a hypoechoic mass (reported as a hematoma, Fig 1A) that partially filled the renal pelvis. As the pyelectasis was found to be progressing in the following days, a percutaneous nephrostomy tube was implanted in the patient, through which hematuria was still detectable. A month later the percutaneous nephrostomy tube’s position and the patient’s urine flow was examined using anterograde pyelography. As a filling defect of a similar size was reported at the site of the previously described lesion (Fig 1B), a contrastenhanced ultrasonography (CEUS) was performed to better characterize the intrarenal mass (Figs 2 and, 3). Following an intensive contrast agent uptake in the arterial phase, the mass showed an early washout, suggesting malignancy. The subsequent core biopsy of the graft indicated a high-grade transitional cell carcinoma. The staging computed tomography (CT) scan showed no lymph node propagation or metastases. The graft was surgically removed (Fig 4), the patient is now on regular dialysis, and the follow-up examinations showed no disease progression by the end of 2018.
DISCUSSION
Following KT, urothelial cancer may appear in the kidney graft, but this condition seems to be extremely rare [11]. These tumors are usually diagnosed in the bladder, ureter/urethra, or in the native kidneys. In men the most frequent location is the native kidneys, while in women TCCs occur more often in the ureter [11,15,16]. Among kidney transplant patients, the prevalence of urothelial tumors is reported to be higher in women (except for bladder cancer). Chinese people are more often affected, which is believed to be associated with the consumption
FARKAS, TÖRÖK, KOVÁCS ET AL
of a traditional herb (in tea form) that contains aristolochic acid [13,16e18]. Following exposure, heterozygous mutations of HRAS (proto-oncogene activation) and deletion or replacement mutations of the TP53 gene (disruption of an anti-oncogenic function) were reported, probably due to aristolochic acid-DNA adduct formation [18]. Human polyoma virus and papilloma viruses 16 and 18 are also associated with TCC in kidney transplant patients [19,20]. The chronic use of Cyclophosphamide should be avoided, as it is also known to increase the risk of TCC [21]. The most common initial symptom of a TCC is painless gross hematuria. Microscopic hematuria, pyuria/urological infection, renal failure due to obstruction, and asymptomatic, accidentally recognized hydronephrosis are also reported [7,11,15,16]. Due to the possible asymptomatic presentation, ultrasonographic follow-up of kidney transplanted patients is required. Following the recognition of a mass in the renal pelvis or bladder, a CT and/or magnetic resonance imaging (MRI) scan is usually performed with the administration of contrast material, even though such substances are known to be nephrotoxic and may lead to graft damage [22e25]. Moreover, a CT scan imposes a radiation burden, and an MRI may entail compatibility issues due to implanted metal objects. CEUS seems to be a good diagnostic alternative. This modality also applies a contrast agent that contains sulfur-hexafluoride gas and phospholipid powder and is administered intravenously. After reconstitution in saline, microbubbles are formed that resonate in the vasculature during ultrasonography, leading to signal generation [26]. Thus, it is possible to carry out a dynamic investigation of the vascularization, circulation, and contrast agent uptake of a lesion or organ. The specificity and sensitivity of CEUS are close to that of contrast-enhanced CT or MRI, with a better cost-benefit ratio. It is easily accessible, does not require radiation, enables immediate diagnosis, and, most importantly, the CEUS contrast agent is not nephrotoxic with the doses used in clinical practice [26].
Fig 1. Ultrasonographic imaging and anterograde pyelography of the kidney graft in the right pelvic area. In the B-mode ultrasonographic picture, (A) pyelectasis and a hypoechogenic mass (white arrowheads) were reported. During an anterograde pyelography, (B) the contrast agent showed dilated calyces and a filling defect in the caudal part of the renal pelvis (white arrowheads). Note the partially obstructed urine flow.
DE NOVO UROTHELIAL CARCINOMA
1283
Fig 2. Contrast-enhanced ultrasonography (CEUS) of the graft (arterial phase). (A) The intrapelvic hypoechogenic mass is visible (white arrowheads). (B) CEUS during the arterial phase revealed an intensive contrast agent uptake in the same location (white arrow).
In conclusion, asymptomatic hydronephrosis or gross painless hematuria signifies the possibility of a TCC in the graft. CEUS is a good alternative to CT or MRI scans with a
similar diagnostic success rate without the associated nephrotoxicity or radiation burden. Early diagnosis is essential for rapid surgical treatment and better survival
Fig 3. CEUS of the graft (venous phase). (A) The intrapelvic hypoechogenic mass is visible (white arrowheads). (B) CEUS during the venous phase revealed an early washout of the contrast agent in the same location (right panel, white arrow).
1284
FARKAS, TÖRÖK, KOVÁCS ET AL
Fig 4. The surgically removed graft with the tumor mass in the renal pelvis. Following the diagnosis using CEUS, histology suggested a high-grade transitional cell carcinoma in the graft so the kidney was surgically removed. The tumor is visible in the renal pelvis, indicated with black arrowheads. Histology and immunochemistry confirmed that it was a transitional cell carcinoma.
rates, for which CEUS offers the possibility of easy access and rapid diagnosis. ACKNOWLEDGMENT Ádám Z. Farkas and Dávid Korda recieved a scholarship (EFOP3.6.3-VEKOP-16-2017-00009 scholarship) as financial support.
REFERENCES [1] Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004;15:1582e8. [2] Rama I, Grinyo JM. Malignancy after renal transplantation: the role of immunosuppression. Nat Rev Nephrol 2010;6:511e9. [3] Penn I. Primary kidney tumors before and after renal transplantation. Transplantation 1995;59:480e5. [4] Nemes B, Toronyi É, Rajczy K, et al. De novo malignant melanoma occured in renal allograft: DNA typing to determine the origin of the tumour. Interv Med Appl Sci 2010;2:31e6. [5] Vegso G, Toth A, Toronyi E, Perner F, Mathe Z. Changes in tumor characteristics in kidney transplanted patients over the last 40 years. Transplant Proc 2015;47:2198e200. [6] Fekecs T, Kadar Z, Battyani Z, et al. Incidence of nonmelanoma skin cancer after human organ transplantation: singlecenter experience in Hungary. Transplant Proc 2010;42:2333e5. [7] Besarani D, Cranston D. Urological malignancy after renal transplantation. BJU Int 2007;100:502e5. [8] Kozma V, Végs} o G, Deák PÁ, et al. Radiofrequency ablation of an intercalyceal neoplasm in a transplanted kidney using percutaneous nephrostomy for coolingdsafety and early result. Interv Med Appl Sci 2010;2:37e41. [9] Vegso G, Toth M, Hidvegi M, et al. Malignancies after renal transplantation during 33 years at a single center. Pathol Oncol Res 2007;13:63e9. [10] Frasca GM, Sandrini S, Cosmai L, et al. Renal cancer in kidney transplanted patients. J Nephrol 2015;28:659e68.
[11] Cox J, Colli JL. Urothelial cancers after renal transplantation. Int Urol Nephrol 2011;43:681e6. [12] Mokos I, Pasini J, Stern-Padovan R, Mrsic S, Ries S. Conservative surgical treatment of low-grade urothelial carcinoma in the renal allograft recipient: a case report. Transplant Proc 2006;38: 1363e5. [13] Gokce MI, Kocaay AF, Akturk S, Tuzuner A. Urothelial carcinoma of the allograft kidney developed in a renal transplant patient. Turk J Urol 2016;42:213e5. [14] Vervloessem I, Oyen R, Vanrenterghem Y, et al. Transitional cell carcinoma in a renal allograft. Eur Radiol 1998;8:936e8. [15] Chiang YJ, Yang PS, Wang HH, et al. Urothelial cancer after renal transplantation: an update. Transplant Proc 2012;44: 744e5. [16] Li XB, Xing NZ, Wang Y, Hu XP, Yin H, Zhang XD. Transitional cell carcinoma in renal transplant recipients: a single center experience. Int J Urol 2008;15:53e7. [17] Liu GM, Fang Q, Ma HS, Sun G, Wang XC. Distinguishing characteristics of urothelial carcinoma in kidney transplant recipients between China and Western countries. Transplant Proc 2013;45:2197e202. [18] Xiao J, Zhu X, Hao GY, et al. Association between urothelial carcinoma after kidney transplantation and aristolochic acid exposure: the potential role of aristolochic acid in HRas and TP53 gene mutations. Transplant Proc 2011;43:3751e4. [19] Luo HL, Chen YT, Huang SC, et al. Human polyomavirus is associated with earlier onset of upper urinary tract urothelial carcinoma in patients after kidney transplantation. Transplant Proc 2017;49:1064e7. [20] Xiao J, Zhu X, Hao GY, et al. Association between urothelial carcinoma after renal transplantation and infection by human papillomavirus types 16 and 18. Transplant Proc 2011;43: 1638e40. [21] Shiga Y, Suzuki K, Tsutsumi M, Ishikawa S. Transitional cell carcinoma of the renal pelvis in a patient with cyclophosphamide therapy for malignant lymphoma: a case report and literature review. Hinyokika Kiyo 2002;48:301e5. [22] Buhaescu I, Izzedine H. Gadolinium-induced nephrotoxicity. Int J Clin Pract 2008;62:1113e8.
DE NOVO UROTHELIAL CARCINOMA [23] Perazella MA. Gadolinium-contrast toxicity in patients with kidney disease: nephrotoxicity and nephrogenic systemic fibrosis. Curr Drug Saf 2008;3:67e75. [24] Barrett BJ. Contrast nephrotoxicity. J Am Soc Nephrol 1994;5:125e37. [25] Granata A, Zanoli L, Insalaco M, et al. Contrast-enhanced ultrasound (CEUS) in nephrology: has the time come for its widespread use? Clin Exp Nephrol 2015;19:606e15.
1285 [26] Westwood M, Joore M, Grutters J, et al. Contrastenhanced ultrasound using SonoVue(R) (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and costeffectiveness analysis. Health Technol Assess 2013;17: 1e243.
ABSTRACT Introduction. Following renal transplantation, the incidence of malignancies is 3e5 times higher than that of healthy individuals. Among other type of cancers, the risk of urological tumors is also elevated. However, only a few cases of de novo transitional cell carcinomas occurring in renal allografts have been reported. Case report. A 63-year-old tertiary transplanted male patient was urgently hospitalized for a painless macroscopic hematuria. Ultrasonography revealed pyelectasis and a hematoma in the renal pelvis. A percutaneous nephrostomy tube was inserted. An anterograde pyelography was performed later, where a filling defect was still observable in the location of the previously reported hypoechoic mass. Contrast-enhanced ultrasonography showed enhancement of the lesion. An ultrasound-guided percutaneous biopsy was performed. The histologic evaluation revealed a high-grade transitional cell carcinoma. A whole-body staging computed tomography scan did not show signs of metastatic disease. The renal allograft was surgically removed. No disease progression was observed during the 21-month follow-up period. Conclusions. Painless hematuria and asymptomatic hydronephrosis occurring after kidney transplantation should raise the possibility of urothelial carcinoma in the kidney graft. Contrast-enhanced ultrasound should be considered as a first-line diagnostic modality because it is easily accessible and does not raise concerns about nephrotoxicity or radiation burden.
T
HE OVERALL incidence of malignancies had been reported to be 3e5 times higher in renal transplant recipients compared to the general population [1]. The main reason for this higher incidence is the permanent immunosuppressive therapy required, especially when induction is administered at the time of transplantation [2]. The most frequent types of malignancies are lymphoproliferative disorders and skin cancers [3e6], followed by urological tumors [7e9]. The majority of de novo urological tumors are renal cell carcinomas arising from the patients’ native kidneys [10]; however, an increased risk of urothelial cancers has also been reported [11]. In this article we report a de novo transitional cell carcinoma (TCC) in a kidney graft, which has an extremely low prevalence and only a few cases have been reported previously [12e14]. ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 1281e1285 (2019)
CASE REPORT Almost 9 years after undergoing a cadaveric kidney transplantation (KT), a tertiary transplanted patient was urgently hospitalized in our department for a painless macroscopic hematuria and elevated serum creatinine level. His medical history consisted of an IgAnephropathy discovered at the age of 18 years. He received his first cadaveric KT in 1986. This kidney graft was removed following a month-long febrile state due to a severe cytomegalovirus
*Address correspondence to Ádám Z. Farkas, Semmelweis University, Department of Transplantation and Surgery, 1082 Budapest, Baross utca 23-25, Hungary. Tel: þ36 1 2676000; Fax: þ36 1 3172166. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.04.011
1281
1282 infection. His second cadaveric transplantation was performed in 1990 in Vienna. The patient had chronic allograft injury and underwent a graftectomy 12 years later. He was driven back to regular kidney replacement therapy; however, preparations for a further KT were already decided and carried out in accordance with the patient’s wishes. He received a third cadaveric graft in 2008 (1 HLA-A, 1 HLA-B, 1 HLA-DR antigen match), followed by daclizumab induction therapy. The patient received tacrolimus (4.5 mg), mycophenolic acid (2 500 mg) and prednisolone (5 mg) as maintenance immunosuppression. Following his admittance in 2017, a Doppler ultrasonography of the kidney graft was performed that revealed pyelectasis and a hypoechoic mass (reported as a hematoma, Fig 1A) that partially filled the renal pelvis. As the pyelectasis was found to be progressing in the following days, a percutaneous nephrostomy tube was implanted in the patient, through which hematuria was still detectable. A month later the percutaneous nephrostomy tube’s position and the patient’s urine flow was examined using anterograde pyelography. As a filling defect of a similar size was reported at the site of the previously described lesion (Fig 1B), a contrastenhanced ultrasonography (CEUS) was performed to better characterize the intrarenal mass (Figs 2 and, 3). Following an intensive contrast agent uptake in the arterial phase, the mass showed an early washout, suggesting malignancy. The subsequent core biopsy of the graft indicated a high-grade transitional cell carcinoma. The staging computed tomography (CT) scan showed no lymph node propagation or metastases. The graft was surgically removed (Fig 4), the patient is now on regular dialysis, and the follow-up examinations showed no disease progression by the end of 2018.
DISCUSSION
Following KT, urothelial cancer may appear in the kidney graft, but this condition seems to be extremely rare [11]. These tumors are usually diagnosed in the bladder, ureter/urethra, or in the native kidneys. In men the most frequent location is the native kidneys, while in women TCCs occur more often in the ureter [11,15,16]. Among kidney transplant patients, the prevalence of urothelial tumors is reported to be higher in women (except for bladder cancer). Chinese people are more often affected, which is believed to be associated with the consumption
FARKAS, TÖRÖK, KOVÁCS ET AL
of a traditional herb (in tea form) that contains aristolochic acid [13,16e18]. Following exposure, heterozygous mutations of HRAS (proto-oncogene activation) and deletion or replacement mutations of the TP53 gene (disruption of an anti-oncogenic function) were reported, probably due to aristolochic acid-DNA adduct formation [18]. Human polyoma virus and papilloma viruses 16 and 18 are also associated with TCC in kidney transplant patients [19,20]. The chronic use of Cyclophosphamide should be avoided, as it is also known to increase the risk of TCC [21]. The most common initial symptom of a TCC is painless gross hematuria. Microscopic hematuria, pyuria/urological infection, renal failure due to obstruction, and asymptomatic, accidentally recognized hydronephrosis are also reported [7,11,15,16]. Due to the possible asymptomatic presentation, ultrasonographic follow-up of kidney transplanted patients is required. Following the recognition of a mass in the renal pelvis or bladder, a CT and/or magnetic resonance imaging (MRI) scan is usually performed with the administration of contrast material, even though such substances are known to be nephrotoxic and may lead to graft damage [22e25]. Moreover, a CT scan imposes a radiation burden, and an MRI may entail compatibility issues due to implanted metal objects. CEUS seems to be a good diagnostic alternative. This modality also applies a contrast agent that contains sulfur-hexafluoride gas and phospholipid powder and is administered intravenously. After reconstitution in saline, microbubbles are formed that resonate in the vasculature during ultrasonography, leading to signal generation [26]. Thus, it is possible to carry out a dynamic investigation of the vascularization, circulation, and contrast agent uptake of a lesion or organ. The specificity and sensitivity of CEUS are close to that of contrast-enhanced CT or MRI, with a better cost-benefit ratio. It is easily accessible, does not require radiation, enables immediate diagnosis, and, most importantly, the CEUS contrast agent is not nephrotoxic with the doses used in clinical practice [26].
Fig 1. Ultrasonographic imaging and anterograde pyelography of the kidney graft in the right pelvic area. In the B-mode ultrasonographic picture, (A) pyelectasis and a hypoechogenic mass (white arrowheads) were reported. During an anterograde pyelography, (B) the contrast agent showed dilated calyces and a filling defect in the caudal part of the renal pelvis (white arrowheads). Note the partially obstructed urine flow.
DE NOVO UROTHELIAL CARCINOMA
1283
Fig 2. Contrast-enhanced ultrasonography (CEUS) of the graft (arterial phase). (A) The intrapelvic hypoechogenic mass is visible (white arrowheads). (B) CEUS during the arterial phase revealed an intensive contrast agent uptake in the same location (white arrow).
In conclusion, asymptomatic hydronephrosis or gross painless hematuria signifies the possibility of a TCC in the graft. CEUS is a good alternative to CT or MRI scans with a
similar diagnostic success rate without the associated nephrotoxicity or radiation burden. Early diagnosis is essential for rapid surgical treatment and better survival
Fig 3. CEUS of the graft (venous phase). (A) The intrapelvic hypoechogenic mass is visible (white arrowheads). (B) CEUS during the venous phase revealed an early washout of the contrast agent in the same location (right panel, white arrow).
1284
FARKAS, TÖRÖK, KOVÁCS ET AL
Fig 4. The surgically removed graft with the tumor mass in the renal pelvis. Following the diagnosis using CEUS, histology suggested a high-grade transitional cell carcinoma in the graft so the kidney was surgically removed. The tumor is visible in the renal pelvis, indicated with black arrowheads. Histology and immunochemistry confirmed that it was a transitional cell carcinoma.
rates, for which CEUS offers the possibility of easy access and rapid diagnosis. ACKNOWLEDGMENT Ádám Z. Farkas and Dávid Korda recieved a scholarship (EFOP3.6.3-VEKOP-16-2017-00009 scholarship) as financial support.
REFERENCES [1] Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004;15:1582e8. [2] Rama I, Grinyo JM. Malignancy after renal transplantation: the role of immunosuppression. Nat Rev Nephrol 2010;6:511e9. [3] Penn I. Primary kidney tumors before and after renal transplantation. Transplantation 1995;59:480e5. [4] Nemes B, Toronyi É, Rajczy K, et al. De novo malignant melanoma occured in renal allograft: DNA typing to determine the origin of the tumour. Interv Med Appl Sci 2010;2:31e6. [5] Vegso G, Toth A, Toronyi E, Perner F, Mathe Z. Changes in tumor characteristics in kidney transplanted patients over the last 40 years. Transplant Proc 2015;47:2198e200. [6] Fekecs T, Kadar Z, Battyani Z, et al. Incidence of nonmelanoma skin cancer after human organ transplantation: singlecenter experience in Hungary. Transplant Proc 2010;42:2333e5. [7] Besarani D, Cranston D. Urological malignancy after renal transplantation. BJU Int 2007;100:502e5. [8] Kozma V, Végs} o G, Deák PÁ, et al. Radiofrequency ablation of an intercalyceal neoplasm in a transplanted kidney using percutaneous nephrostomy for coolingdsafety and early result. Interv Med Appl Sci 2010;2:37e41. [9] Vegso G, Toth M, Hidvegi M, et al. Malignancies after renal transplantation during 33 years at a single center. Pathol Oncol Res 2007;13:63e9. [10] Frasca GM, Sandrini S, Cosmai L, et al. Renal cancer in kidney transplanted patients. J Nephrol 2015;28:659e68.
[11] Cox J, Colli JL. Urothelial cancers after renal transplantation. Int Urol Nephrol 2011;43:681e6. [12] Mokos I, Pasini J, Stern-Padovan R, Mrsic S, Ries S. Conservative surgical treatment of low-grade urothelial carcinoma in the renal allograft recipient: a case report. Transplant Proc 2006;38: 1363e5. [13] Gokce MI, Kocaay AF, Akturk S, Tuzuner A. Urothelial carcinoma of the allograft kidney developed in a renal transplant patient. Turk J Urol 2016;42:213e5. [14] Vervloessem I, Oyen R, Vanrenterghem Y, et al. Transitional cell carcinoma in a renal allograft. Eur Radiol 1998;8:936e8. [15] Chiang YJ, Yang PS, Wang HH, et al. Urothelial cancer after renal transplantation: an update. Transplant Proc 2012;44: 744e5. [16] Li XB, Xing NZ, Wang Y, Hu XP, Yin H, Zhang XD. Transitional cell carcinoma in renal transplant recipients: a single center experience. Int J Urol 2008;15:53e7. [17] Liu GM, Fang Q, Ma HS, Sun G, Wang XC. Distinguishing characteristics of urothelial carcinoma in kidney transplant recipients between China and Western countries. Transplant Proc 2013;45:2197e202. [18] Xiao J, Zhu X, Hao GY, et al. Association between urothelial carcinoma after kidney transplantation and aristolochic acid exposure: the potential role of aristolochic acid in HRas and TP53 gene mutations. Transplant Proc 2011;43:3751e4. [19] Luo HL, Chen YT, Huang SC, et al. Human polyomavirus is associated with earlier onset of upper urinary tract urothelial carcinoma in patients after kidney transplantation. Transplant Proc 2017;49:1064e7. [20] Xiao J, Zhu X, Hao GY, et al. Association between urothelial carcinoma after renal transplantation and infection by human papillomavirus types 16 and 18. Transplant Proc 2011;43: 1638e40. [21] Shiga Y, Suzuki K, Tsutsumi M, Ishikawa S. Transitional cell carcinoma of the renal pelvis in a patient with cyclophosphamide therapy for malignant lymphoma: a case report and literature review. Hinyokika Kiyo 2002;48:301e5. [22] Buhaescu I, Izzedine H. Gadolinium-induced nephrotoxicity. Int J Clin Pract 2008;62:1113e8.
DE NOVO UROTHELIAL CARCINOMA [23] Perazella MA. Gadolinium-contrast toxicity in patients with kidney disease: nephrotoxicity and nephrogenic systemic fibrosis. Curr Drug Saf 2008;3:67e75. [24] Barrett BJ. Contrast nephrotoxicity. J Am Soc Nephrol 1994;5:125e37. [25] Granata A, Zanoli L, Insalaco M, et al. Contrast-enhanced ultrasound (CEUS) in nephrology: has the time come for its widespread use? Clin Exp Nephrol 2015;19:606e15.
1285 [26] Westwood M, Joore M, Grutters J, et al. Contrastenhanced ultrasound using SonoVue(R) (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and costeffectiveness analysis. Health Technol Assess 2013;17: 1e243.