AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Problem

Upper tract urothelial tumors of the renal pelvis and ureters are relatively rare. Tumors of the renal pelvis account for approximately 10% of all renal tumors and approximately 5% of all urothelial tumors. Ureteral tumors are even more uncommon, occurring with one quarter the incidence of renal pelvis tumors. Transitional cell carcinoma (TCC) accounts for more than 90% of upper tract urothelial tumors.

Frequency

• The mean age of occurrence is 65 years.
• Incidence of TCC increases with age. Moreover, tumors rarely are found at autopsy.
• Upper tract urothelial tumors occur more frequently in men, with a male-to-female ratio of 3:1.
• Upper tract urothelial tumors occur more frequently in white people as compared to black people, with a white-to-black ratio of 2:1.
• An association exists between upper tract TCC and Balkan nephropathy. Balkan nephropathy is a degenerative interstitial nephritis of unknown etiology that confers a 100- to 200-times greater increase in the incidence of upper tract TCC in individuals from rural Balkan areas relative to that observed in individuals residing in neighboring communities. Tumors generally are low grade, multiple, and bilateral compared with TCC of other etiologies.

Etiology

Tobacco smoking is the factor most strongly associated with upper tract TCC and confers a greater than 3-fold increase in risk. Estimates point to smoking as the cause of 70% of upper tract tumors in men and 40% in women.

Drinking coffee causes a slight increase in risk of upper tract TCC. This tends to be observed in people who consume more than 7 cups of coffee per day.

Analgesic abuse also is a risk factor for urothelial malignancy. It is independent and synergistic with renal papillary necrosis. Long-term exposure to analgesics induces a nephropathy that is associated with an incidence of upper tract TCC as high as 70%. The pathognomonic finding for analgesic abuse, called capillarosclerosis, is found in 15% of patients with upper tract tumors.

Occupational exposure to agents utilized in the petrochemical, plastic, and tar industries has been linked to increased risk of TCC.

Chronic infections, irritation, and calculi also may predispose a patient to develop squamous cell carcinoma and, less commonly, adenocarcinoma of the upper urinary tract.

Cyclophosphamide has been linked to the development of urothelial tumors. More specifically, a breakdown metabolite called acrolein is thought to be the causative agent. When implicated, the associated tumors tend to be high grade.

Finally, heredity may play a part in the development of TCC. An association exists with Lynch syndrome II, a syndrome that includes the early onset of proximal colonic nonpolyposis tumors, numerous synchronous and metachronous colon tumors, and extracolonic tumors.

Pathophysiology

Upper tract tumor types

TCC is the most common histology observed, accounting for greater than 90% of upper tract urothelial tumors. TCCs are strongly associated with smoking.

Squamous cell carcinoma comprises 1-7% of upper tract urothelial tumors. Squamous cell carcinoma frequently is associated with infected staghorn calculi that have been present for a long duration. Affected patients frequently present with moderately to poorly differentiated tumors and advanced disease.

Adenocarcinoma is observed in less than 1% of upper tract tumors. Patients with adenocarcinoma of the upper tracts also may have associated calculi and long-term obstruction, suggesting an etiologic origin for these processes.

Inverted papilloma is an unusual lesion. This generally is considered a benign histologic lesion, but it may harbor foci of malignant change.

Patterns of spread

Transitional tumors spread conventionally in a cephalad to caudad direction. For instance, studies have shown a high rate of recurrence in the distal ureteral stump in patients treated with nephrectomy and incomplete ureterectomy. Conversely, TCC rarely recurs proximal to the level of resection of a ureteral lesion. Approximately 30-75% of patients with upper tract urothelial tumors develop bladder tumors at some point in their cancer course.

Lymphatic extension is another pattern observed with TCC. The most common locations for spread, depending on the site of the primary tumor, are paraaortic, paracaval, ipsilateral common iliac, and the pelvic lymph nodes.

Hematogenous seeding also occurs, with common sites for metastases including the liver, lung, and bone.

Distribution of upper tract transitional cell carcinoma

• Renal pelvis - 58%
• Ureter - 35% (73% of which are located in the distal ureter)
• Both renal pelvis and ureter - 7%
• Bilateral involvement - 2-5%

Clinical

• Gross or microscopic hematuria (75%) is the most common clinical presentation.
• Flank pain (18%) results from gradual obstruction/distention of the collecting system or acute colic from obstruction by a blood clot.
• Dysuria (6%): Some patients may complain of irritative lower urinary tract symptomatology such as burning with urination.
• Weight loss, anorexia, flank mass, or bone pain are symptoms of advanced disease that are manifest in a minority of patients.

INDICATIONS

Section 3 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

• Nephroureterectomy with excision of the bladder cuff is indicated in patients with renal pelvis TCC, regionally extensive disease, and high-grade or high-stage lesions.
• Benefits associated with laparoscopic nephroureterectomy include decreased patient analgesic requirements, shorter hospitalization, and improved cosmetic results. Short-term follow-up has shown that laparoscopic nephroureterectomy appears to offer equivalent cancer control to that of the open procedure.
• Segmental ureterectomy coupled with ureteral reimplantation can be used for lower-grade superficial urothelial tumors located in the distal ureter.
• Renal-sparing surgery, including segmental ureterectomy and endoscopic therapy, typically is used in patients with small, lower-grade superficial lesions. Additionally, patients who would be at risk for dialysis after nephroureterectomy and those who are medically unfit for radical surgery are generally treated with minimally invasive and renal-sparing techniques.

RELEVANT ANATOMY

Section 4 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Renal pelvis

The renal pelvis is the portion of the urinary collecting system formed by the confluence of 2 or 3 major calices.

Ureter

The ureter is a 20- to 30-cm tubular structure lying on the psoas muscle. It follows an S-shaped curve, passing medially to the sacroiliac joint and then coursing laterally near the ischial spine before passing medially to penetrate the base of the bladder. It passes through a submucosal tunnel to empty into the bladder.

Histology

The renal pelvis and ureter are lined by a transitional epithelium. The next layer is the lamina propria. External to the lamina propria is smooth muscle arranged in a spiral and longitudinal manner. The outermost adventitia is composed of fibrous connective tissue.

CONTRAINDICATIONS

Section 5 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Relative contraindications that must be addressed prior to surgical treatment include the presence of active infection, uncorrected bleeding disorders, renal insufficiency, severe comorbidities, and advanced age. In the presence of advanced metastatic disease, surgical treatment generally is not warranted and medical management (ie, chemotherapy) should be employed.

WORKUP

Section 6 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Lab Studies

• Urinalysis - To confirm hematuria and to rule out a coexistent urinary tract infection
• Basic metabolic panel - To check serum creatinine (assess renal function) and electrolytes
• Activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR) - To check baseline coagulation status

Imaging Studies

• Excretory urography
• • This test commonly is referred to as an intravenous pyelogram (IVP). IVP and cystoscopy comprise the standard workup for a patient who presents with microscopic or gross hematuria. IVP is used to evaluate the upper urothelial tract, and cystoscopy evaluates the lower urinary system (ie, bladder).
  • Approximately 50-75% of patients have a radiolucent filling defect that is characteristically irregular and in continuity with the wall of the collecting system (see Image 1).
  • Approximately 10-30% of patients have a tumor that causes obstruction or nonvisualization of the collecting system.
• CT scan
• • A noncontrast CT scan can be performed, followed by a contrast study. A CT urogram with digital reconstruction has replaced the IVP at some institutions. Plain films, which demonstrate drainage and anatomy, can also be performed after the CT scan.
  • TCCs usually are present as an irregular filling defect. They tend to be hypovascular when compared to the rest of the kidney and demonstrate minimal increased density (enhancement) following intravenous contrast injection (see Image 2 and Image 3).
  • CT scan has limited value in staging TCC because stage Ta and T2 cannot be differentiated. CT scan, however, is helpful in demonstrating peripelvic or periureteral tumor extension, thereby assisting with staging of aggressive disease.
• Similar to CT scan, MRI also is of limited use in staging early TCC; however, it may be of greater usefulness in more advanced disease.

Other Tests

• Cytopathology
• • Voided urine samples obtained for cytopathology lack sensitivity, especially for low-grade tumors for which cytology is read as normal in as many as 80% of patients.
  • Sensitivity increases for higher-grade tumors, which tend to shed more tumor cells. Cytology is accurate in diagnosing 83% of patients with grade IV disease.
  • Selective washings of both the upper tracts and the bladder can be accomplished to aid in tumor localization. Cytology plays a role in urothelial tumor surveillance in conjunction with cystoscopy/ureteroscopy.

Diagnostic Procedures

• Cystoscopy
• • Cystoscopy is a procedure whereby a small fiberoptic scope is inserted through the urethra in order to visualize the bladder. This ambulatory/clinic procedure usually is well tolerated by both women and men. A 16F flexible cystoscope typically is used in men, whereas women can undergo either rigid or flexible cystoscopic examination.
  • This procedure is mandatory to rule out coexistent bladder lesions.
  • It is also essential for postoperative surveillance to monitor for bladder tumor development.
• Retrograde urography
• • Retrograde urography is a procedure whereby contrast is injected into the ureteral orifice with the aid of a cystoscope (see Image 4). This can be performed with fluoroscopic guidance or with standard x-ray film plates.
  • This procedure allows better visualization of the collecting system than excretory urography by increasing the distention of the urinary collecting system. Retrograde pyelography is preferable in patients with azotemia and/or contrast allergy.
  • Overall, this technique is more than 75% accurate in establishing the diagnosis of urothelial cancer.
• Ureteropyeloscopy
• • Since the advent of rigid and flexible ureteroscopes, this procedure is used increasingly for the diagnosis of upper tract urothelial tumors.
  • Biopsy forceps or cytology brushings can be used to collect tissue.
  • This procedure has 86% accuracy in diagnosing renal pelvis tumors and 90% accuracy in diagnosing ureteral tumors.
  • The complication rate associated with ureteropyeloscopy is approximately 7%. Several complications associated with this procedure include perforation, complete disruption, and ureteral stricture.
• Percutaneous nephroscopy is not indicated for diagnosis because of the theoretical risk of tumor cell implantation in the retroperitoneum and nephrostomy tube tract.

Staging

The distribution of tumor stages and grades differs from study to study. The majority of tumors are low-grade low-stage TCCs. In one study, almost 60% of tumors were grade I or II, and 70% of tumors were stage Tis/Ta through T2. Stage I disease was found in 96% of patients with grade I upper tract TCC.¹

Grading (I-IV): Pathological assignments range from grade 1 for well-differentiated tumors to grade 4 for poorly differentiated tumors.

Staging: Stages are based on the depth of tumor invasion and are classified using the tumor, node, metastases (TNM) system.

• Tis - Carcinoma in situ
• Ta - Superficial/papillary
• T1 - Lamina propria invasion
• T2 - Muscularis propria invasion
• T3 - Peripelvic/periureteral/renal invasion
• T4 - Contiguous organ involvement
• N0 - Negative nodes
• N1 - Metastasis in single node less than 2 cm in diameter
• N2 - Metastasis in single node 2-5 cm in diameter or metastasis to multiple nodes less than 5 cm in diameter
• N3 - Metastasis in lymph node greater than 5 cm in diameter
• M0 - No distant metastasis
• M1 - Distant metastasis

TREATMENT

Section 7 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Medical therapy

Medical treatment of superficial upper tract urothelial tumors involves the topical instillation of the chemotherapeutic agents mitomycin C, thiotepa, or bacille Calmette-Guérin (BCG). These agents can be administered either percutaneously, through a ureteral catheter, or intravesically in patients with vesicoureteral reflux. Topical instillation therapy is most appropriate for patients with multiple superficial disease, carcinoma in situ, bilateral disease and/or limited renal function. The safety of these agents as adjuvant therapy has been well studied; however, their efficacy in decreasing recurrence rates, delaying tumor progression, and improving survival rates has not been firmly established. Furthermore, the administration of these agents often requires hospitalization and skilled nursing to prevent hyperperfusion and systemic absorption.

• Superficial (Ta, T1), grades 1-3, and carcinoma in situ
• • Adjuvant topical treatments include the retrograde or percutaneous instillation of mitomycin, thiotepa, doxorubicin (Adriamycin), and BCG.
  • Efficacy of these agents in treating upper-tract urothelial carcinoma is not well established because of the small retrospective studies with heterogeneous patients and tumor characteristics.
  • BCG is an attenuated form of Mycobacterium tuberculosis, and its use carries a small but significant risk of BCG sepsis. To prevent systemic side effects, BCG should not be administered in the presence of hematuria. Recurrence rates in the literature following percutaneous retrograde administration of BCG have ranged from 12.5-28.5% after a follow-up period of between 4 and 59 months.
  • Keeley and Bagley reported on the use of mitomycin administered via a retrograde catheter in 19 patients.² They noted a 54% recurrence rate at a mean follow-up of 30 months. No patient had disease progression.
  • See reported on the efficacy and safety of Adriamycin as adjuvant therapy in 12 patients.³ Of the 10 patients evaluated, 50% had disease-free upper tracts at 4-53 months. In this series, Adriamycin was given via continuous infusion to improve dwell time and efficacy. No treatment-related toxicities were observed.
  • Bropirimine has also been used as an oral agent with limited success.
  • Prospective randomized studies are needed to determine the efficacy and optimal use of these agents as adjuvant therapy for superficial upper-tract TCC.
• Muscle invasive (T2) and locally advanced (T3-T4) disease
• • Chemotherapy
  • • MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) has been standard treatment. However, the survival advantage is modest, and optimal dosing is often limited because of severe toxicity.
    • Gemcitabine with cisplatin (GC) has shown similar response rates, time to progression, and survival as those of MVAC but with less toxicity. Gemcitabine with cisplatin is now considered first-line therapy.
  • Adjuvant and neoadjuvant chemotherapy
  • • Neoadjuvant combination chemotherapy (gemcitabine, paclitaxel, carboplatin) is under phase II investigation in patients with advanced urothelial tumors.
    • The efficacy of neoadjuvant chemotherapy for lower-tract urothelial carcinoma may apply to upper-tract disease; however, randomized studies have not been performed.
  • Radiation
  • • In contrast to lower-tract disease, radiation generally plays a palliative role in controlling pain and hemorrhage associated with advanced upper-tract urothelial carcinoma.
    • Shipley et al recently reported on the use of adjuvant radiotherapy after resection of T3 or T4 and/or node-positive upper-tract TCC. In this retrospective analysis of 31 patients treated from 1970-1997, radiation with the concurrent use of cisplatin chemotherapy improved 5-year survival rates.
    • Prospective studies are needed to better define the role of radiation therapy in the multimodal management of upper-tract TCC.
• Metastatic and node-positive disease
• • Chemotherapy
  • • MVAC has been the standard treatment; however, the survival advantage is minimal to moderate, and optimal dosing is often limited because of severe toxicity.
    • Gemcitabine with cisplatin has shown similar response rates, time to progression, and survival as those of MVAC but with less toxicity. Gemcitabine with cisplatin is now considered first-line therapy.
    • Sorafenib, an antiangiogenesis molecule and inhibitor of multiple kinases, including Ras kinase, is being evaluated in phase II clinical trials in patients with advanced or metastatic TCC of the bladder, ureter, or renal pelvis. The drugs are effective in advanced renal and other cancers. Members of the Ras kinase superfamily are commonly mutated in TCC and important in proliferation.

Surgical therapy

Nephroureterectomy with excision of the bladder cuff is considered the standard therapy. This surgical procedure is indicated in patients with renal pelvis TCC, regionally extensive disease, and high-grade or high-stage lesions.

Segmental ureterectomy coupled with ureteral reimplantation is indicated for patients with ureteral tumors located in the distal ureter, generally of lower grade and stage. Unfortunately, because of the multifocal nature of TCC, the ipsilateral recurrence rate is 25% after segmental ureterectomy.

Renal-sparing surgery, including segmental ureterectomy and endoscopic therapy, maintains a vital role in the management of upper-tract urothelial tumors. Typically, patients with small, low-grade superficial lesions are the best candidates for this approach. Some investigators use this approach more frequently in patients with a solitary kidney, bilateral disease, compromised renal function, or greater baseline operative risk.

• Open radical nephroureterectomy
• • Nephroureterectomy is the criterion standard operation for large, high-grade (grade 3) tumors of the renal pelvis and proximal ureter that are organ-confined or locally advanced. Nephroureterectomy is also recommended for multifocal, recurrent, grade 1-2 tumors, which are found to be less amenable to ureteroscopic management.
  • This procedure involves removal of the kidney, ureter, and bladder cuff via a thoracoabdominal or flank approach with a separate lower quadrant Gibson incision.
  • Care is taken to excise the entire distal ureter and bladder cuff to prevent local recurrence.
  • Lymphadenectomy, which requires little additional operative time, is performed for staging purposes and potentially offers a therapeutic benefit.
• Laparoscopic nephroureterectomy
• • The indications and oncologic surgical principles for laparoscopic nephroureterectomy (LNU) are similar to those of the open approach.
  • Pure laparoscopic transperitoneal and retroperitoneal approaches, as well as hand-assisted laparoscopic approaches have been described. The optimal technique depends largely on surgeon experience.
  • Laparoscopic nephroureterectomy is the preferred approach of 73% of urologists surveyed for the treatment of large, high-grade renal pelvic/upper-ureteral TCC.
  • Optimal management of the bladder cuff remains controversial. Some investigators prefer hand-assisted laparoscopic en bloc excision of the distal ureter with closure of cystotomy defect.
  • Operative time is comparable with that of the standard open procedure.
  • Laparoscopic nephroureterectomy offers the benefits of minimally invasive surgery, including less blood loss, decreased narcotic analgesia requirements, shorter hospitalization, rapid return to normal activity, and improved cosmetic result.
• Distal ureterectomy: High-grade and/or large distal ureteral tumors are most commonly managed with distal ureterectomy with ureterovesical reimplant.
• Ureteroscopic treatment
• • Ureteroscopy offers a renal-preserving alternative to traditional nephroureterectomy and is used in patients with compromised renal function, bilateral upper-tract disease, or other medical contraindications to nephroureterectomy. Ureteroscopic ablation is now the preferred choice for low-grade upper-tract TCC.
  • Ureteroscopy allows biopsy and treatment of tumors along the entire upper urinary tract. Cold-cup biopsy forceps or flat-wire basket is used for tissue diagnosis and to determine tumor grade to plan for future intervention.
  • The use of Nd:YAG and Ho:YAG lasers, as well as small 2F-3F electrosurgical devices enable ureteroscopic resection, coagulation, and ablation of upper-tract tumors under direct vision.
  • The following are technical considerations for ureteroscopic treatment of upper-tract tumors:⁴
  • • Obtain adequate tissue during initial biopsy for accurate diagnosis and grade.
    • Minimize the risk of stricture with the use of laser rather than the more deeply penetrating electrosurgical devices when ablating ureteral tumors.
    • Drain the bladder with a small catheter or use a ureteral access sheath to improve flow and visibility, which can be limited by bleeding.
    • Facilitate resection by slowing the respiratory rate, which decreases movement and stabilizes the operative field during resection and ablation.
• Percutaneous treatment
• • Percutaneous therapy allows the use of larger scopes with improved maneuverability and visibility to ablate larger tumors in the renal pelvis and upper ureter. Percutaneous access may be used to administer topical therapeutic agents such as BCG, mitomycin, or Adriamycin. This approach is an acceptable alternative to nephroureterectomy in patients with low-to-moderate–grade grade disease. However, as with all organ-preserving strategies, vigilant follow-up surveillance is required.
  • Percutaneous techniques allow a renal-sparing approach, and are well suited for large-volume disease of the kidney, renal pelvis, and proximal ureter.
  • Percutaneous access to the diseased renal unit is established, followed by tract dilation to allow the passage of nephroscopes, laser fibers, biopsy forceps, and electrosurgical devices to completely resect and ablate tumors under direct vision.
  • This approach allows better visibility and passage of larger scopes and instruments to facilitate biopsy and treatment of larger and more bulky tumors than ureteroscopy allows.
  • Percutaneous access also allows for a deeper resection and more accurate staging than ureteroscopy for tumors of the renal pelvis and kidney.
  • Tumor seeding of the nephrostomy tract, although rare, has been reported and is associated with high-grade lesions.
  • Recurrence rates by grade are as follows: grade I, 18%; grade II, 33%; and grade III, 50%.

Follow-up

Follow-up is largely determined by tumor grade and stage. More frequent assessment is warranted for patients with higher-grade or higher-stage lesions. Surveillance ureteroscopy under local anesthesia in the clinic is feasible and well tolerated in selected patients. The high rate of recurrence mandates a strict postoperative surveillance for any renal-sparing treatment strategy that deals with upper-tract urothelial tumors.

A standard surveillance protocol consists of cystoscopy and selective urine cytology at 3-month intervals postoperatively for the first year and every 6 months during the second year. Excretory urography or retrograde ureteropyelography can be performed at 3- to 6-month intervals to evaluate the upper tract. Ureteroscopy is the most sensitive tool in detecting recurrence and is performed routinely at 3-month intervals initially, with the frequency increasing to 6 months after the first year. At 2-5 years, cystoscopy and ureteroscopy are continued at 6-month intervals.

• As mentioned above, ureteroscopy is the preferred surveillance tool in detecting recurrences after endoscopic ablation of upper-tract TCC.
• Ureteroscopy with biopsy and cytology has a sensitivity of 93.4% and specificity of 65.2%. In the same series, surveillance with retrograde pyelography had a sensitivity and specificity of 71.7% and 84.7%, respectively.
• Voided urine cytology and microscopic hematuria have a low sensitivity but reasonable specificity in detecting upper-tract recurrences.
• Upon any recurrence, the endoscopic cycle is restarted.
• The contralateral collecting system is studied radiographically once yearly with retrograde pyelography or IVP and cytology.
• Surveillance cystoscopy and imaging of the contralateral upper tract is also required to detect recurrences in patients treated with nephroureterectomy.
• Several novel markers in addition to urine cytology may be helpful in detecting recurrent urothelial carcinoma. A recent prospective study reported urinary fibrinogen/fibrin degradation products (FDPs), bladder tumor antigen (BTA), and urine cytology to have sensitivities of 100%, 50%, and 29%, respectively, in detecting upper-tract TCC. Specificity was 83%, 62%, and 59% for FDP, BTA, and cytology, respectively.⁵

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Bladder Cancer, Blood in the Urine, Intravenous Pyelogram, and Cystoscopy.

COMPLICATIONS

Section 8 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Complications related to nontreatment

• Disease progression
• Obstruction
• Bleeding
• Infection
• Metastasis
• Death
• See Image 5 and Image 6

Treatment-related complications

• Open nephroureterectomy: Surgery has potential risks, which include bleeding, infection, injury to surrounding bowel or viscera, and abdominal wall laxity resulting from neuropraxia. Open procedures have an increased incidence of postoperative pulmonary complications relative to laparoscopic approach.
• Laparoscopic nephroureterectomy: Bleeding, infection, injury to surrounding bowel or viscera, and port site hernia are several complications to fully discuss with patients during the informed consent process.
• Endoscopic surgery: Ureteral perforation, delayed ureteral stricture, extraluminal tumor spillage, or tumor propagation are several complications associated with endoscopic surgery. Also, a lack of reliability in staging tumors exists. Percutaneous surgery has a risk of immediate and delayed bleeding, a theoretical risk of tumor seeding, and a risk of pleural cavity violation, potentially resulting in hydrothorax that will necessitate chest tube drainage.
• Medical therapy: Instillation of topical chemotherapeutic agents is associated with collecting system scarring, obstruction, systemic absorption, sepsis, or toxic agranulocytosis resulting from heightened perfusion pressures. Medical therapy has a similar complication profile to that of nontreatment.

OUTCOME AND PROGNOSIS

Section 9 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Total nephroureterectomy (5-year survival by stage)

• Stage Tis, Ta, T1 - 91%
• Stage T2 - 43%
• Stage T3/T4 or N1/N2 - 23%
• Stage N3/M1 - 0%

On multivariate analysis, only stage and age were significant prognostic factors for survival. The type of surgical procedure (radical versus renal-sparing) approached significance. Most evidence suggests that for small, low-grade/low-stage tumors, equivalent results are achieved with either a renal-sparing procedure or nephroureterectomy. In one recent study of ureteroscopic management of 23 patients with mostly low-to-intermediate–grade upper tract tumors, all patients were alive without evidence of disease progression with a 35-month mean follow-up period.⁶ Evidence demonstrates that patients with grade III lesions cannot be cured with less than radical surgery.

FUTURE AND CONTROVERSIES

Section 10 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

• Laparoscopic nephroureterectomy (with or without hand assist) will play an increasing role as the procedure of choice for renal pelvis or high-grade tumors.
• Urologists will utilize endoscopic ablative procedures with increasing frequency for low-grade low-stage disease and in patients for whom renal-sparing therapy is indicated.
• New agents for topical instillation therapy of upper tract urothelial tumors are being developed.
• One area of great research interest and possible clinical applicability is that of diagnostic and prognostic markers for TCC. These are being developed for bladder cancer and may be useful in detecting upper-tract cancers. In one recent study, survivin, a protein apoptosis inhibitor, was measured in the urine of patients with TCC of the bladder. Urinary survivin levels were highly sensitive and specific in this small study.⁷ The bladder tumor–associated analytes (BTA) test, CYFRA 21-1, and NMP22 may have a role in patients at risk for recurrent bladder cancer. Fluorescence in situ hybridization (FISH) may be one of the more useful tests for detecting urinary tract cancer, as it has a greater sensitivity for lower-grade tumors than cytology and other tests. Ureteral cancer has been detected with this assay during evaluation for hematuria.⁸

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Media file 1:  Intravenous pyelogram (IVP) demonstrating an upper calyx filling defect characteristic of transitional cell carcinoma (TCC). Blunting of the involved calyx is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  X-RAY

Media file 2:  CT scan demonstrating right renal pelvis transitional cell carcinoma (TCC). Contrast in the renal pelvis is displaced by the tumor. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  CT

Media file 3:  CT scan demonstrating left distal ureteral transitional cell carcinoma (TCC). The left ureter is dilated and a medial filling defect is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  CT

Media file 4:  Left retrograde ureterogram demonstrating the classic "goblet" sign of ureteral transitional cell carcinoma (TCC). Ureteral dilation distally and proximally to the tumor is present. The narrowed wall of the ureter is irregular. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  X-RAY

Media file 5:  CT scan demonstrating bulky right renal pelvis transitional cell carcinoma (TCC) replacing the majority of the renal parenchyma. A pericaval lymph node metastasis is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  CT

Media file 6:  CT scan demonstrating metastatic transitional cell carcinoma (TCC) of the right adrenal gland. A heterogeneous adrenal mass is noted adjacent to the spine. The superior portion of the right kidney is observed. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
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Media type:  CT

Media file 7:  Treatment algorithm for managing upper-tract transitional cell carcinoma (TCC).
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Media type:  Graph

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

1. Hall MC, Womack S, Sagalowsky AI. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. Oct 1998;52(4):594-601. [Medline].
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Article Last Updated: Nov 26, 2007