Scott G. Hubosky, MD
BASICS
DESCRIPTION
• Radiographic diagnosis of a radiolucent entity occupying the confines of the upper urinary tract including the intrarenal collecting system or ureter, as seen against contrast within the intraluminal space
• The finding itself is nonspecific but may represent malignant or benign processes
• Ureteroscopic evaluation is the gold standard to establish definitive diagnosis
EPIDEMIOLOGY
Incidence
• Difficult to define given the nonspecific nature of the radiographic finding
– Upper tract urothelial carcinoma (UTUC)
Estimated 5,900–7,300 new cases in USA in 2014 (1)[C]
Prevalence
• Nephrolithiasis
– Reported prevalence of kidney stones in USA between 1976 and 1994 was 13% in men and 7% in women (2)[C]
RISK FACTORS
• For UTUC
– History of smoking
– History of urothelial carcinoma of the bladder
– Gene carrier or family history of Lynch syndrome (hereditary nonpolyposis colorectal cancer)
• For nephrolithiasis
– Previous stone history
– Chronic dehydration
– Dietary factors
Elevated sodium intake
Purine gluttony
• For sloughed papilla
– NSAID overuse
– Sickle cell disease or trait
– History of diabetes
• For fungus ball
– Immunosuppression
Genetics
N/A
PATHOPHYSIOLOGY
Depends on underlying etiology
ASSOCIATED CONDITIONS
• Hematuria
– Gross
– Microscopic
• Flank pain
GENERAL PREVENTION
• Depends on underlying etiology
– UTUC
Smoking cessation/avoidance
– Nephrolithiasis
Adequate hydration
Diet and lifestyle modification to prevent future stone formation
DIAGNOSIS
HISTORY
• Flank pain or renal colic
• Hematuria
– Gross
– Microscopic
• Pre-existing malignancy
• History or urinary diversion
• Prior urinary tract manipulation (stent, stone treatment, etc.)
PHYSICAL EXAM
• Costovertebral angle tenderness
• Patient may by asymptomatic
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis
• Urine cytology may suggest malignancy
• Urine culture including fungal cultures
• Serum creatinine/BUN
Imaging
• Filling defects are found in imaging modalities which utilize contrast that fills the intrarenal collecting system
– Intravenous injection of contrast
CT urogram
MR urogram
IVP
Invasive arteriograms (cardiac catheterization, aortogram, etc.)
– Intraluminal administration of contrast
Retrograde pyelogram
Antegrade nephrostogram
Cystogram (if reflux present)
Diagnostic Procedures/Surgery
Ureteroscopic evaluation is required to obtain definitive diagnosis and provides for direct visual inspection with relatively low morbidity (3)[C]
Pathologic Findings
Depends on underlying etiology
DIFFERENTIAL DIAGNOSIS
• Malignant lesions
– UTUC
– Rare primary cancers of the upper urothelial surface
Squamous cell carcinoma (often associated with chronic untreated infected staghorn calculi)
Adenocarcinoma
Inverted papilloma (about 15% have malignant components)
Sarcoma
Leiomyosarcoma
Angiosarcoma
Small cell carcinoma
– Metastatic carcinoma
Melanoma
Renal cell carcinoma
• Benign lesions
– Air: Iatrogenic, infectious, fistula
– Blood clot
– Fibroepithelial polyp
– Fungus ball
– Hemangioma
– Inflammatory lesions: Granuloma, malakoplakia, TB
– Inverted papilloma
– Calculus (usually radiolucent)
– Benign tumors (rare): Leiomyoma, neurofibroma, cholesteatoma
– Extrinsic compression of the ureter
– Mucous (urinary diversion patients)
– Protein matrix
– Ureteritis or pyelitis cystica
– Vascular impression
– Fibroepithelial polyp
– Papilla
Prominent papilla (ectopic or end on; normal anatomic variant)
Sloughed papilla (may cause obstruction or hematuria)
– Foreign body
Stent fragment (retained)
Staple/clip (more likely with urinary diversion)
TREATMENT
GENERAL MEASURES
• If any doubt exists about the etiology of the filling defect then diagnostic ureteroscopy is indicated
• Prominent papilla may appear as filling defects in the very peripheral aspect of renal calyces in an “end on” position
MEDICATION
First Line
• For stones composed purely of uric acid manifesting as filling defects, alkalization of the urine can be attempted and if pH of 6.5 or greater is achieved then uric acids may dissolve over time
– Potassium citrate
– Sodium bicarbonate
Second Line
N/A
SURGERY/OTHER PROCEDURES
• UTUC
– For low-grade UTUC which can be reached ureteroscopically and completely ablated, 5-yr survival is equal to radical nephroureterectomy (4)[C]
After complete ablation, local recurrence can be seen in up to 75% of patients if followed for at least 5 yr.
Progression of low-grade to high-grade disease occurs in about 15% of cases
These points should be stressed to patients when counseling on the management of UTUC
– For high-grade UTUC or very large-volume low-grade UTUC, radical extirpative surgery is considered the gold standard for cancer control
Nephroureterectomy (open or laparoscopic)
Segmental ureterectomy
• Nephrolithiasis
– Ureteroscopy with laser lithotripsy
– ESWL with or without retrograde pyelogram to assist with localization or with ultrasound guidance
– PCNL
• Sloughed papilla
– Ureteroscopy confirms diagnosis
Papilla can be removed primarily with ureteroscopic grasper or basket
Coagulation with cautery or laser will achieve hemostasis
Avoid overuse of NSAIDs
• Fibroepithelial polyp
– Can be removed with ureteroscopy using laser or grasper
• Fungus ball
– Can be removed with ureteroscopy or percutaneous approach
– Antifungals
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• UTUC
– Neoadjuvant chemotherapy is currently under investigation for suspected high-stage disease with preliminary data suggesting down staging on pathologic specimens
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Depends on underlying etiology
– Prognosis usually excellent for benign conditions
– UTUC (prognosis depends on pathologic staging) (5)[C]. TNM pathologic staging and prognosis is as follows:
pTo, pTa, and pTis have 93% and 89% cancer-specific survival at 5 and 10 yr
pT1 has 91% and 85% cancer-specific survival at 5 and 10 yr
pT2 has 75% and 70% cancer-specific survival at 5 and 10 yr
pT3 has 54% and 45% cancer-specific survival at 5 and 10 yr
pT4 has 12% and 6% cancer-specific survival at 5 and 10 yr
COMPLICATIONS
N/A
FOLLOW-UP
Patient Monitoring
• UTUC
– For those undergoing ureteroscopic conservative treatment, regular surveillance including cystoscopy and ureteroscopy is required given high chance of local recurrence
– Cross-sectional imaging (CT or MRI) is recommended to check for locally advancing disease
– For those undergoing radical nephroureterectomy (NU), surveillance cystoscopy and cross-sectional imaging are also needed on a regular basis
• Nephrolithiasis
– Renal ultrasound, serum electrolyte testing
– For patients at high risk for stone recurrence, 24-hr urine electrolyte evaluation
Patient Resources
N/A
REFERENCES
1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.
2. Stamatelou KK, Francis ME, Jones CA, et al. Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int. 2003;63:1817.
3. Conlin MJ. Diagnostic ureteroscopy. In: Smith AD, et al. Smith’s Textbook of Endourology. 3rd ed. Chichester: Wiley and Blackwell, 2012.
4. Grasso M, Fishman AI, Cohen J, et al. Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: A 15-year comprehensive review of 160 consecutive patients. BJU Int. 2012;110:1618–1626.
5. Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: A series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115:1224–1233.
ADDITIONAL READING
• Hubosky SG, Boman BM, Charles S, et al. Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). BJU Int.2013;112(6):813–819. doi: 10.1111/bju.12008
• Matin SF, Margulis V, Kamat A, et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract urothelial cell carcinoma. Cancer. 2010;116:3127–3134.
• Stower MJ, MacIver AG, Gingell JC, et al. Inverted papilloma of the ureter with malignant change. BJU. 1990;65:13.
• Xu AD, Ng CS, Kamat A, et al. Significance of upper urinary tract urothelial thickening and filling defect seen on MDCT urography in patients with a history of urothelial neoplasms. Am J Roentgenol. 2010;195:959–965.
See Also (Topic, Algorithm, Media)
• Fibroepithelial Polyp, Genitourinary
• Filling Defect, Upper Urinary Tract (Renal Pelvis and Ureter) Image 
• Fungal Infections, Genitourinary
• Reference Tables: TNM: Renal Pelvis and Ureter Cancer
• Ureter and Renal Pelvic Tumors, General Considerations
• Ureter and Renal Pelvis, Squamous Cell Carcinoma
• Ureter and Renal Pelvis, Urothelial Carcinoma
• Urolithiasis, Ureteral
CODES
ICD9
• 189.1 Malignant neoplasm of renal pelvis
• 189.2 Malignant neoplasm of ureter
• 793.5 Nonspecific (abnormal) findings on radiological and other examination of genitourinary organs
ICD10
• C65.9 Malignant neoplasm of unspecified renal pelvis
• C66.9 Malignant neoplasm of unspecified ureter
• R93.4 Abnormal findings on diagnostic imaging of urinary organs
CLINICAL/SURGICAL PEARLS
• Up to 40% of patients with an upper tract urothelial carcinoma will develop urothelial carcinoma of the bladder.
• Ureteroscopy can be both diagnostic and therapeutic.