TUMORS OF THE URETER

Tumors of the ureter are uncommon, accounting for less than 1% of all
genitourinary malignant lesions. They are seen twice as often in men as in women,
and most patients are in the sixth or seventh decade of life at the time of diagnosis.
Although there is no predilection to side, the lesion most commonly occurs in the
lower ureter (70% of cases).
Etiology
The origin of these tumors is believed to be similar to that of other urothelial
tumors. Schmauz aid Cole (1974) have shown that the relative risks for developing
ureteral carcinoma are increased in cigarette smokers, coffee drinkers, and leather
workers. Only at high-level exposure are the carcinogens apt to be active, since their
transit time through the ureter is so rapid.
Pathogenesis & Pathology
Most tumors arising primarily within the intact ureter are transitional cell
carcinomas (93%); only5K are squamous cell carcinomas. However, squamous cell
carcinomas are seen more frequently when malignant disease develops in the stump
of the ureter following nephrectomy for nonmalignant disease. Primary
adenocarcinoma of the ureter is rare. When adenocarcinoma is found in the ureter, it
is probably metastasis from the gastrointestinal tract, uterine cervix, lung, or prostate.
From 56 to 80% of ureteral tumors are papillary is opposed to solid. About
50% of the tumors are of iniei-mediate grade (II), and only 10% are of low grade, UK
degree of anaplasia closely parallels the extent of invasion and is important in
determining the prognosis,
Ureteral carcinomas spread to invade neighboring structures and organs (intestines,
psoas muscle, iliac vessels); through the lymphatic to invade the pelvic, para-aortic,
inguinal, and supraclavicular lymph nodes; and through the vascular to the lungs,
bones, and liver. Distant metastases are usually observed within 2 years in all patients
with regional lymph node metastases.

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Tumor Staging
The staging system is based on surgical findings and is a modification of that
suggested by Batata el. al.
A. Symptoms: The most common symptom is hematuria, which occurs in 59-99% of
patients and is intermittent and sometimes quite profuse, pain is observed in 20-50%
of patients. Passage of clots down the ureter causes acute and severe pain. Symptoms
of bladder irritation (frequency, urgency, and dysuria) are reported in 10-52% of
patients. Less frequently, as a result of metastatic disease, patients may complain of
leg edema, pain from nerve root involvement, or constitutional symptoms. The tumor
is silent in 12-26% of-patients and is discovered on excretory urograms.
B. Signs: Physical findings are usually absent. A palpable mass, caused by ureteral
obstruction and the resulting hydronephrosis, is present in 7-50% of patients. If renal
infection has supervened, the renal mass may be tender. Supraclavicular adenopathy
or hepatomegaly may be felt if metastasis has occurred.
C. Laboratory Findings: Anemia may be found if bleeding is prolonged or severe.
Gross or microscopic hematuria is usually present. Evidence of infection may be seen
on urinalysis. If metastasis has occurred, the results of liver profile studies or the
alkaline phosphatase level may be abnormal.
D. X-Ray Findings: The excretory urogram usually shows abnormal findings in all
patients with carcinoma of the ureter. The 2 most common urographic findings are an
intraluminal filling defect and hydronephrosis, with or without hydroureter. In many
of patients, the kidney on the affected side is nonfunctioning and fails to visualize.
Angiography is of little value because of the avascular nature of most such of tumors.
E. UItrasonography and CT Scanning: these procedures help to establish diagnosis.
F. Instrumental Examination: If the patient is bleeding, cystoscopy should be
performed immediately in order to locate the source of the blood, during cystoscopy,
the ureteral tumor is seen in 6-18% of patients. In these clients, biopsy confirms the
diagnosis, catheterization, performed to collect urine for cytological examination and
to better define ureteral lesion through retrograde ureterograms, is usually helpful in
diagnosis. In retrograde studies, several signs have been considered diagnostic for

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ureteral tumors: (1) the Chevassu-Mock sign, ie, increased ureteral bleeding
following manipulation at the site of the rumor; (2) Marion's sign, ie, drainage of
clear urine after the ureteral catheter passes above the tumor; and (3) Bergman's sign,
ie, coiling of the ureteral catheter in the distal area below the tumor. Usually,
however, the occluding-tip ureteropyelogram remains the best method for
demonstrating the nature and extent of the lesion.
G. Cytologic Examination: Urine should be collected either as a freshly voided
specimen or through the retrograde catheter from the affected side prior to injecting
the contrast medium. Unfortunately, cytologic studies, including those using
retrograde dull urine collections, have significant (30%) false-negative results in
patients with ureteral carcinoma. However, when the retrograde brushing technique
de-veloped by Gill, Lu, and Bibbo (1978) is used, the material obtained and
examined histologically and cytologically usually confirms the diagnosis of ureteral
and is discovered on excretory urograms or cured by means of a Dormia stone basket
(Kiriyama, Hironaka, and Fukuda, 1976).
Differential Diagnosis
Ureteral calculus may cause the same symptoms and signs as ureteral tumor if the
calculus is radiolucent. The urogram in each instance shows a negative (black)
shadow in the ureter and a dilated tract above it. Stone is suggested if a grating
feeling is noted as a catheter is passed by it. Ultrasonography (Arger et al. 1979) or
CT scanning should differentiate nonopaque stone from tumor. The correct diagnosis
may be possible only at surgery. Ureteral stenosis, often secondary to compression by
masses of lymph nodes involved by cancer (eg, cervical), can mimic ureteral tumor.
CT scanning may reveal the involved nodes. A blood clot from a renal stone, a
sloughed papilla, a renal adenocarcinoma, or a pelvic tumor also shows as a negative
shadow within the ureter. The urograms should provide the differentiation. Air
bubbles introduced through a ureteral catheter may be a source of confusion.
Treatment
A. Specific Measures: In the absence of demonstrable metastases,
nephroureterectomy with resection of the periureteral bladder wall and adjacent

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vesical mucosa remains standard therapy. However, in patients with-noninvasive
low-grade tumors of the lower ureter, distal ureterectomy with reimplantation may be
considered (Johnson and Babaian, 1979). Partial ureterectomy for lesions located
elsewhere in the ureter (middle- or upper-third) carries with it a high risk of tumor
developing later below the line of resection therefore, local resection should be
avoided. Resection of a tumor through a ureterotomy should be performed only for
fibrous ureteral polyps (these are usually diagnosed by x-ray findings of a long,
narrow, and generally smooth-filling ureteral defect without evidence of obstruction
or renal damage).
Postoperative irradiation of the ureteral bed (4500 rads in 5 weeks) has been used
successfully to reduce local recurrence in a small number of patients with high-grade
invasive tumors of the distal ureter (Babaian, Johnson, and Chan, 1980).
Radiotherapy has been well tolerated and has caused no long-term complications.
Results of combination therapy for invasive tumors of the distal ureter, consisting of
preoperative irradiation (5000 rads given in 25 fractions over 5 weeks) followed
within 4-6 weeks by nephroureterectomy and excision of a bladder cuff, have
likewise been encouraging, but further experience is still required.
B. Palliative Measures: If metastases are present, surgery is seldom justified unless it
is required to relieve pain caused by obstruction or to control intractable bleeding.
Radiotherapy, 6000 rads given in 30 fractions over 6 weeks, usually controls the local
tumor. Chemotherapy is restricted to treating known metastatic lesions (lungs, liver,
bones, etc); the drug programs parallel those in current use for patients with
metastases from bladder cancer.
C. Follow-Up Care: The patient should be followed closely during the first several
years to exclude local recurrences, visceral metastases, or late bladder tumors.
Subsequent metastatic disease may be expected in approximately 40% of patients. In
addition, the development of vesical malignant disease in more than 40% of patients
requires that endoscopy be an integral part of the follow-up examinations. (See also
the section on follow-up care for tumors of the renal pelvis, above.)

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 Prognosis
The prognosis for patients with ureteral carcinoma tends to be better than for patients
with carcinoma of the renal pelvis (5-year survival rates of 67% and 53%,
respectively), but the prognosis varies widely according to the grade of tumor and
stage of disease. Patients presenting with metastatic disease usually die in less than 3
years.

References:
1. Donald R. Smith, M.D. General Urology, 11-th edition, 1984.
2. O.F.Vozianov, O.V.Lyulko. Urinology.- Kyiv: Vischa shkola, 1993.
3. Urinology edited by N.A.Lopatkin, Moscow, 1982.
4. Scientific Foundations of Urology. Third Edition 1990. Edited by Geoffrey D.
Chisholm and William R. Fair, MD. Heinemann Medical Books, Oxford.
5. Levi F, La-Vecchia C, Randimbison L, Franceschi S: Incidence of infiltrating
cancer following superficial bladder carcinoma. Int J Cancer 1993:55:419-421.
6. Kiemeney LA, Witjes JA, Verbeek AL, Heijbroek RP, Debruyne FM: The clinical
epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological
Group. Br J Cancer 1993:67:806-812.
7. Silverman DT, Levin LI, Hoover RN, Hartge P: Occupational risks of bladder
cancer in the United States. J Natl Cancer Inst 1989:81:1472-1483.
8. Silverman DT, Morrison AS, Devesa SS: Epidemiology of bladder cancer; in
Fraumeni JF, Schottenfeld D (eds): Cancer Epidemiology and Prevention. New York,
Oxford University Press, 1996, pp 1156-1179.
9. La Vecchia C, Negri E: Nutrition and bladder cancer. Cancer Causes Control
1996:7:95-100.
10. Viscoli CM, Lachs MS, Horwitz RI: Bladder cancer and coffee drinking: A
summary of case-control research. Lancet 1993:341:1432-1437.

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11. King WD, Marrett LD: Case-control study of bladder cancer and chlorination by-
products in treated water (Ontario, Canada). Cancer Causes Control 1996;7:596-604.
12. Bates MN, Smith AH, Cantor KP: Case-control study of bladder cancer and
arsenic in drinking water. Am J Epidemiol 1995;141:523-530.
13. Kaldor JM, Day NE, Kittelmann B, Pettersson F, Langmark F, Pedersen D, Prior
R Neal F, Karjalainen S, Bell J: Bladder tumours following chemotherapy and
radiotherapy for ovarian cancer: A case-control study. Int J Cancer 1995;63: 1-6.
14. Bartsch H, Malveille C, Friesen M, Kadlubar FF, Vineis P: Black (air-cured) and
blond (flue-cured) tobacco cancer risk.IV: Molecular dosimetry studies implicate
aromatic amines as bladder carcinogens. Eur J Cancer 1993;29A: 1199-1207.
15. Chinegwundoh FI, Kaisary AV: Polymorphism and smoking in bladder
carcinogenesis. Br J Urol 1996;77:672-675.
Cancer Inst 1994;86:712-716.
16. Abdel-Rahman SZ, Anwar WA, Abdel-Aal WE, Mostafa HM, Au WW: GSTM1
and GSTT1 genes are potential risk modifiers for bladder cancer. Cancer Detect Prev
1998;22: 129-138.
17. Carpenter AA: Clinical experience with transitional cell carcinoma of the bladder
with special reference to smoking. J Urol 1989;141:527-528.
18. Pacchioni D, Martone T, Ghisolfi G, Bussolati G, Tizzani A, Casetta G, Vineis P:
Tobacco smoke, recurrences, and p53/bcl-2 expression in bladder cancer.
Carcinogenesis 1997:18:1659-1661.
19. Wakai K, Ohno Y, Obata K, Aoki K: Prognostic significance of selected lifestyle
factors in urinary bladder cancer. Jpn J Cancer Res 1991;84:1223-1229.
20. Fleming CM, Kaisary A, Wilkinson GR, Smith P, Branch RA: The ability to 4-
hydroxyIate debrisoquine is related to recurrence of bladder cancer.
Pharmacogenetics 1992; 2:128-134.