Transitional cell carcinoma is the most common type of tumor in the renal pelvis and ureter. Its etiology, pathology, clinical manifestations, and treatment principles are similar to those of bladder tumors. In China, the incidence of transitional cell carcinoma in the renal pelvis is higher than reported in other countries. Among renal tumors, renal pelvis carcinoma generally accounts for less than 10%, but according to statistics from the Third National Urology Academic Conference in China, it accounts for 24%. The likelihood of tumors occurring in urothelial organs varies, with bladder tumors being the most common and other organs less so. Upper urinary tract urothelial tumors are more frequently reported in China than abroad. The carcinogens affecting urothelial organs are the same, and urothelial tumors have a tendency to occur in multiple organs, often developing in the direction of urine flow. Statistics from the First Clinical Hospital of Beijing Medical University show that 92% of cases follow the direction of urine flow, while only 8% occur against it. Literature reports that 30–50% of upper urinary tract tumors later develop into bladder cancer, whereas bladder cancer leads to upper urinary tract tumors in only 2–3% of cases. The bladder, being the largest organ in the urinary system with prolonged urine retention, activates hydrolytic enzymes that convert substances into carcinogens, resulting in a much higher likelihood of tumor development compared to other organs. In bladder cancer resection specimens, 10% show carcinoma in situ at the distal end of the ureter. Thus, it can be hypothesized that if bladder cancer patients survive longer, more cases of upper urinary tract carcinoma may be detected.

Chemically carcinogenic substances related to bladder cancer will be discussed in detail in the next section.

Balkan nephropathy is an interstitial nephritis and a common disease cause of renal pelvis urethra cancer, exhibiting distinct regional characteristics in areas such as Yugoslavia, Romania, Bulgaria, and Greece, with even village-to-village boundaries. It progresses slowly, leads to renal function decline, and affects both genders similarly, with bilateral occurrence in 10% of cases. Investigations into environmental, occupational, and genetic factors have been conducted, but the cause remains unclear. Due to the susceptibility to renal function injury, superficial and multifocal nature, treatment should aim to preserve renal tissue as much as possible.

Analgesics can cause renal pelvis cancer, and recent studies suggest that acetaninophen (Tylenol) metabolites possess carcinogenic properties. Carcinogenesis from analgesics typically requires cumulative consumption exceeding 5 kg, equivalent to the carcinogenic risk of smoking 15 cigarettes daily for 20 years.

Chronic irritation, such as inflammation caused by urinary stones, can lead to renal pelvis cancer, with the majority being squamous cell carcinoma. Over 50% of squamous cell carcinoma patients have a history of stones.

Familial clustering has been observed. McCullough reported a case of a father and his two sons developing multiple upper urinary tract tumors, while Gitte documented three brothers with multiple tumors, initially presenting with bladder tumors. Familial clustering may be associated with viral infections, metabolic abnormalities, and exposure to carcinogens.

The pathological staging is similar to bladder tumors.

The National Cancer Association UICC Jewett

T _is 0 Carcinoma in situ

T _a 0 Papillary carcinoma of the mucous membrane

T ₁ A Infiltration of the lamina propria

T ₂ B ₁ Infiltration of the superficial muscle layer

T _3a B ₂ Infiltration of the deep muscle layer

T _3b C Infiltration of perivesical fat

T ₄ D Infiltration of adjacent organs

The degree of tumor cell differentiation is often the same as the stage, determining the treatment method and its prognosis.

Renal pelvis and urethral cancers metastasize to nearby similar adjacent lymph nodes due to their diffuse and indistinct lymphatic drainage, with an uncertain range. They can also metastasize to bones, kidneys, adrenal glands, pancreas, spleen, liver, lungs, etc.

bubble_chart Clinical Manifestations

The male-to-female ratio is 2:1, with 80% of cases occurring between the ages of 40 and 70, and an average age of 55. Hematuria is the most common initial symptom, visible to the naked eye, intermittent, and painless. If blood clots pass through the ureter, they may cause renal colicky pain, with worm-like blood streaks. Sometimes, patients present with dull pain in the lumbar region.

Most patients show no obvious positive signs, but about 7% exhibit cachexia, which is indicative of advanced-stage cases. In 5–15% of cases, an enlarged kidney may be palpable, possibly accompanied by costovertebral angle tenderness. Reports indicate that 10–15% of patients have no clinical symptoms and are only incidentally discovered during examinations for other diseases.

Renal pelvis and urethral cancer have a tendency for multi-organ involvement and may present with bladder irritation symptoms, such as those seen in bladder tumors. Local spread may lead to varicocele, retroperitoneal psoas sign, and other manifestations. Squamous cell carcinoma often presents with symptoms resembling stones or infections.

1. Excretory urography: Filling defects may be observed and should be differentiated from uric acid stones and matrix stones. Sometimes the defects may be caused by blood clots. Kidney excess parenchymal tumors and cysts can both present with filling defects in the renal pelvis and calyces, and sometimes B-ultrasound and CT are required for definitive diagnosis. Small filling defects in the renal pelvis may be caused by kidney stirred pulse and its branches. Tumors can lead to non-visualization of the ureter, especially in cases of ureteral tumors. Statistics show that when renal pelvic carcinoma is not visualized, one-third are high-stage (invasive) carcinomas. When urethra cancer causes non-visualization, 60–80% are invasive. Hydronephrosis accounts for 35%, and among cases with ureteral filling defects, 20% are found to have hydronephrosis. In 85% of cases with normal urography, the tumors are low-stage.

When excretory urography is unsatisfactory, retrograde urography or other examinations should be performed.

2. Retrograde urography: Its importance lies in: ① Providing clearer imaging, especially when excretory urography is unsatisfactory; ② Possibly observing bleeding from the ureteral orifice on the affected side or protrusion of a lower ureteral tumor into the ureteral orifice; ③ Directly collecting urine from the affected side for tumor cytology or brush biopsy; ④ Bladder cystoscopy to rule out bladder tumors.

During retrograde urography, excessive contrast agent in the renal pelvis may obscure small filling defects. For ureteral imaging, the entire ureter must be filled to confirm the diagnosis. Bulb-tip ureterography, where the ureteral catheter tip resembles an olive or acorn, is inserted into the ureteral orifice under fluoroscopy, and contrast is injected. The tumor may be pushed upward, with the lower ureter dilated like a "goblet." In cases of stones, the lower ureter does not dilate. Invasive tumors have an irregular surface, and edema associated with urinary stones may lead to misdiagnosis. Occasionally, urinary stones may coexist with tumors. Ureteral polyps often present as smooth, elongated filling defects, sometimes with branches.

Ureteral tumors may cause the catheter to bend or form loops. If the catheter passes through the tumor, clear urine may be found above the tumor, while hematuria flows alongside the catheter.

Care must be taken to avoid introducing air bubbles during imaging to prevent misdiagnosis.

3. Brush biopsy: When clinical suspicion of a tumor exists but cytology is negative, brush biopsy can be performed after intravenous contrast injection at the suspected site. A small brush is passed through an F5 catheter, and tissue may adhere to the brush bristles. After removing the brush, small tissue fragments may be present in the ureteral catheter outflow. Repeated flushing with a small amount of saline can collect the fluid for examination. The ureteral catheter should be left in place overnight before removal.

4. Ultrasound examination: Can differentiate between stones and soft tissue lesions, but distinguishing tumors from necrotic papillae, blood clots, or matrix stones is difficult. Ultrasound is unreliable for diagnosing ureteral lesions.

5. CT: Can differentiate between transitional cell carcinoma in the renal pelvis and calyces and kidney cancer. Renal pelvic carcinoma presents as: ① A solid mass in the renal pelvis or globular calyces, with displacement and compression of the renal sinus fat; ② Minimal enhancement after contrast injection; ③ A curved line of contrast around the tumor; ④ Enhanced kidney excess parenchyma (when the tumor is large and affects drainage); ⑤ Preservation of renal contour.

6. Kidney stirred pulse angiography: Can detect thinning or obstruction of intrarenal stirred pulse vessels, often indicating infiltration. Tumors larger than 3 cm may show bleeding.

7. Ureteroscopy and pyeloscopy: May be used for diagnosis and treatment. Pyeloscopy may cause tumor seeding, and its practical value remains inconclusive.

8. Magnetic resonance imaging (MRI): Can differentiate between kidney cancer and renal pelvic carcinoma and is also useful for diagnosing ureteral lesions without requiring contrast agents (suitable for patients with contrast allergies). The diagnostic accuracy may improve with the development of contrast agents.

9. Cytology: Well-differentiated, low-stage tumors have an 80% false-negative rate, while poorly differentiated tumors show 60% positivity or high suspicion.

bubble_chart Treatment Measures

Renal urethra cancer has a 50-year history of performing nephroureterectomy, including the bladder wall segment. If the entire length of the ureter is not removed, the possibility of tumor occurrence in the ureter is as high as 84%. Among 17 cases of renal pelvis cancer with residual ureter, 7 cases (41.2%) developed tumors at the residual end within three years, with half occurring within one year. Some believe it is due to renal pelvis cancer seeding into the ureter, but in reality, it is because of the multifocal nature of the tumor, with carcinogenic effects based on seeding.

Recent understanding, with advances in the knowledge of tumor biological characteristics, indicates that surgery for renal ureteral tumors cannot be one-size-fits-all. For low-stage, low-grade renal urethra cancer, partial nephroureterectomy and radical surgery yield similar outcomes. However, high-stage, high-grade cancers require radical surgery; otherwise, cure is unlikely, especially in cases with positive cytology. Some advocate partial resection for localized high-stage, high-grade cancer, but ultimately, 90% of these patients die from cancer, compared to only 30% for those who undergo radical surgery. Ureterectomy must include the bladder wall segment; otherwise, 60% may develop bladder cancer. Should radical surgery include lymph node dissection? Generally, the answer is no, as few patients with lymph node metastasis survive beyond one year.

For solitary kidneys or bilateral tumors, if they are low-stage, low-grade with negative urine cytology, efforts should be made to preserve as much renal tissue as possible. For high-stage, high-grade cases, radical surgery under dialysis is recommended. Sometimes, for cytology-negative, low-grade tumors, percutaneous pyeloscopy with tumor resection is performed. Partial ureterectomy with kidney preservation accounts for about 20% of ureteral tumor cases.

The 5-year survival rate for non-invasive renal pelvis cancer is 40–59%, while for invasive, poorly differentiated cases, it is 10–25%. Peking University Health Science Center reports a 5-year survival rate of 60.3% after renal pelvis cancer surgery.

As mentioned earlier, renal pelvis and ureteral tumors are prone to organ recurrence, necessitating close follow-up. Some recommend urine cytology every 6 months and bladder cystoscopy for 2 years.

When treating renal ureteral tumors, it is crucial to differentiate them from ureteral polyps. Ureteral polyps are benign urothelial-covered mesenchymal tissues with long stalks, possibly branching, appearing smooth, and cytologically positive. The tissue contains mixed vascular and fibrous components; those rich in vessels are called "hemangiomas," while those with more fibrous tissue are termed "fibromas." Polyps are more common in young people.