JOSE BENITO A. ABRAHAM, ABELARDO M. PRODIGALIDAD.
National Kidney and Transplant Institute Division of Urology, QC, Philippines

Keywords: Malignant Ureteral Obstruction, Metastatic Obstrucgtive Uropathy, Palliative Urinary Diversion

Purpose: To determine the clinical profile of patients with metastatic or malignant ureteral obstruction (MUO), the various urinary diversions used and the clinical outcome of the various therapeutic options administered.

Materials and Methods: The clinical records of all patients admitted at our institution from January 1989 until October 1996 with a primary diagnosis of malignancy and clinically documented metastatic ureteral obstruction were reviewed and the different clinical parameters are summarized.

Results: A total of 96 patients had metastatic malignant ureteral obstruction. 72 underwent urinary diversions in the form of retrograde stenting, percutaneous nephrostomy tube insertions with or without antegrade stenting and surgical diversions. The most common malignancy was cervical cancer (39%) and obstruction is bilateral in 44% of cases. The most successfully employed diversion was percutaneous nephrostomy (75%). To determine clinical outcome, patients were grouped into two: Group A--requiring dialysis treatment prior to diversion and Group B--non-dialyzable prior to diversion. Clinical improvement after urinary diversion was noted in 80% of cases as manifested by betterment of renal function and resolution of symptoms. Various causes of death were mostly related to metastatic disease. Others included sepsis and pulmonary congestion. Complications of urinary diversions were seen in 31% of cases and these were appropriately managed.

Conclusions: Various malignancies lead to obstructive uropathy. When appropriately applied in these patients with advanced disease, urinary diversions are useful in improving renal function and avoiding the complications of uraemia.

Malignant ureteral obstruction continues to be a pressing problem to the urologist and is in fact, one of the few significant urologic emergencies. Indeed, both the problem of uraemia and the debilitating effects of progressively advanced malignancy pose a threat to the suffering patient. Throughout the past decade, there has been a remarkable improvement in the endoscopic and percutaneous techniques used to relieve ureteral obstruction and these techniques have been applied for palliation in patients with advanced malignancy. Many reports agree with this concept and to date, the improvement in the patients’ quality of life after diversion is a documented fact.^{2, 4, 5, 6, 8, 10, 11,12, 14, 17, 18,,19, 20,22, 24,25}

These diversions are commonly in the form of retrograde ureteral stenting, percutaneous drainage with or without antegrade ureteral stenting and open diversions.

Newer techniques had been proposed in recent times. Pauer¹⁶ in 1992, Fleuckiger⁷ in 1993 and VanSonnenberg²² in 1994 proposed the use of expandable metallic wallstents. Recent reports have also been made of extracorporeal²¹ and subcutaneous techniques^{1, 13, 15}. These innovations aim to eliminate the need for a nephrostomy tube and an external appliance. The use of medical management such as corticosteroid therapy was also discussed by Hamdy⁹ and Walsh²³. When these have been proven effective in more patients, they will definitely add to further improve the patients’ quality of life.

Indeed, relief of urinary tract obstruction can be achieved safely with rapid restoration and salvage of renal function.

The objectives of this paper are to determine the clinical profile of patients with metastatic malignant ureteral obstruction, the various urinary diversions employed and the clinical outcome of the various therapeutic options administered.

The clinical records of all patients admitted from January 1989 up to October 1996 with a primary diagnosis of malignancy and coexistent obstructive uropathy were retrieved using the hospital computer database. A total of 101 charts were initially reviewed. Of these, only 96 patients with proven malignancy and clinically proven metastatic ureteral obstruction were included in the study. Five patients were excluded from the study because the coexistent obstructive uropathy was unrelated to their malignancy: three patients (2-bronchogenic cancer, 1-cervical cancer) had urinary stone disease, one case of prostatic cancer had a diabetic neuropathic bladder with secondary vesicoureteral reflux, and one patient with cervical cancer had left hydronephrosis due to a ureteropelvic junction stenosis.

The different types and incidence of malignancy, laterality of ureteral obstruction, various urinary diversions used and the therapeutic outcome of each were summarized and tabulated. In evaluating for clinical improvement after urinary diversion, two groups of patients were identified: those requiring dialysis support prior to diversion (Group A) and those who had a normal creatinine or were azotemic but had no indications for dialysis support (Group B). Clinical improvement of patients in Group A meant being weaned from dialysis after diversion while those in Group B meant improvement or resolution of their symptoms, decrease in baseline creatinine or increase in urine output. The causes of death of the patients who died after diversion were also noted. Finally, the complications encountered are summarized.

A total of 96 patients had metastatic malignant ureteral obstruction. The mean age was 58, (Range of 23-88), with a male: female ratio of 1:2. The primary malignancies were histopathologically proven with biopsy or previous resection of the tumor. Upper tract urinary obstruction was documented via ultrasound, computerized tomography or intravenous pyelogram. The metastatic nature of the ureteral obstruction was ascertained with clinical evidence of tumor compression, retroperitoneal lymph node enlargement or cystoscopic confirmation of tumor involvement of the ureteral orifices. This diagnosis was also confirmed with the clinical assessment of the attending urologists.

Pathology. Of the 96 cases of malignancy, the most common pathology was cervical carcinoma in 38 (39%), followed by bladder cancer in 16 (16%), colo-rectal in 14 (14.5%), prostate in 12 (12.5%), uterine in 4 (4.1%), breast and testes, 3 each (3.1%), lymphoma and gastric, 2 each (2.08%), fallopian tube adenocarcinoma and ovarian, 1 each (1.04%) (table 1). The most common presenting symptoms were anuria or oliguria, flank pains dyspnea, and leg edema and body malaise. The mean admitting creatinine levels was 10.42 mg/dl. Thirty-five (36%) of these patients’ malignancies were diagnosed for the first time simultaneous with the obstructive uropathy during their admission. Sixty one (63%) cases of malignancy were formerly diagnosed months or years earlier and had previously undergone a biopsy or resection of the primary tumor before the occurrence of upper tract dilatation or renal failure. Sixty-six (68%) and thirty (31%) had bilateral and unilateral obstruction, respectively.

Urinary diversions. Of the 96 patients, only a total of 72 underwent urinary diversion (table 2). A preliminary cystoscopy and attempted retrograde pyelography and stenting was done in all but eight patients who underwent an outright percutaneous nephrostomy tube insertion. Retrograde insertion of double-J stents was successful in 11 (15.3%). Five were inserted bilaterally and six unilaterally. Percutaneous nephrostomy tube insertion was subsequently attempted where retrograde stenting failed. This was successfully done in 54 patients (75%), thirty-two (44%) inserted bilaterally and twenty-two (30.5%) unilaterally. Percutaneous nephrostomy with antegrade stenting was successful in 1 (1.38%). Surgical diversions included ureteral exploration with intra-operative double-J stent insertion in one (1.3-%) patient with breast cancer. Open nephrostomy tube insertion was done in one (1.3-%) case of cervical cancer because of a solitary kidney. Ileal conduit was performed in one (1.3-%) case of bladder cancer that was treated with palliative cystectomy and one (1.3-%) cervical cancer. Ureterosigmoidostomy was done after a palliative cystectomy in 2 cases (2.7%) of bladder cancer. The reason for these cases was persistent troublesome bleeding which necessitated transfusions.

Twenty-six patients were not diverted because of the following reasons. Six patients died before any intervention could be administered and four refused treatment. Another six patients with prostatic cancer were treated with hormonal therapy and therefore did not undergo diversion; and ten patients were unfit for the procedures either because of deranged bleeding parameters or poor cardio-pulmonary condition.

Patients undergoing urinary diversions. Two groups of patients were identified: Group A-- those requiring dialysis support prior to diversion and Group B-- those who had normal creatinine levels or azotemic but had no indications for dialysis. A total of 27 patients belonged to Group A. Dialysis treatment was undertaken because of symptoms of uraemia, pulmonary congestion, hyperkalemia, or encephalopathy. Eight underwent emergency acute peritoneal dialysis and nineteen were subjected to hemodialysis. A total of 45 patients belonged to Group B. Of these, 6 (13%) had normal creatinine levels and 39 (86%) were azotemic. Presenting symptoms were similar to Group A and included flank pains, recent-onset oliguria, abdominal pain and edema but there were no positive indications for dialysis. Clinical improvement was manifested by good urine output from the nephrostomy tubes, decreasing creatinine levels and over-all subjective relief of symptoms (e.g. loss of flank pains).

Clinical outcome after urinary diversion. Twenty patients (75%) in Group A were weaned from dialysis after diversion, five (18.5%) remained dialysis-dependent and two (7.4) died of various causes (table 3). Thirty-eight cases in Group B (84%) showed clinical improvement and one (2.2%) showed progressive deterioration of renal function. Six (13.3%) died of various causes (table 4). When combining the two groups and comparing their outcome, a total of 58 patients (81%) had clinical improvement compared to only 6 patients (8%) who manifested no clinical improvement and 8 patients (11%) who died of various causes (table 5).

Various causes of death. Five patients (6.9%) who underwent diversion died of multiple organ failure secondary to complications of metastatic disease to the liver, lungs, mediastinum and intra-abdominal carcinomatosis. Two died of septicemia and one died of pulmonary congestion (table 6).

Complications of urinary diversions. Diversion complications are outlined in table 7. Of those who underwent percutaneous nephrostomy (n=55), dislodgment occurred in 14.5% and had to be replaced, urosepsis in 9%, urine leak from the nephrostomy in 7.2% and clogging in 5.4%. Among those who underwent retrograde stenting (n=11), reinsertion failed in two (18%) patients with cervical cancer requiring conversion to the percutaneous route. Of those who underwent surgical diversions (n=6), urosepsis occurred in one patient who underwent ureterosigmoidostomy, and prolonged ileus in one patient who underwent ileal conduit. The over-all complication rate was 33% for all cases.

Numerous authors had studied obstructive uropathy secondary to metastatic cancer. In diverse retrospective studies conducted at different institutions, the most common primary tumor sites arise mainly from the pelvic organs, particularly cervical carcinoma, bladder, prostate and rectum. Early obstruction is easily explained by extrinsic compression of the ureters by the tumor or by enlarged retroperitoneal lymph nodes. This could also be attributed to contiguous organ invasion involving the ureteral orifices. The laterality of obstruction is also related to this pathogenesis. Most of the pelvic tumors gave rise to bilateral obstruction whereas those primary tumors coming from distant sites mostly result to only unilateral obstruction.

The most common malignancies associated with upper urinary tract obstruction in this study are consistent with existing review of literature. Zadra²⁵ studied 98 patients with malignant obstructive uropathy and found pelvic malignancies to comprise 72.4%. Breast cancer was also mentioned as the most common nonpelvic tumor causing ureteral obstruction. Lau¹² and Teenan²⁰ both studied pelvic malignant disease and noted similar findings. In this study, breast cancer was likewise, the most common non-pelvic tumor together with testicular cancer, followed by lymphoma and gastric carcinoma. The testicular malignancy mentioned here is that of embryonal cell carcinoma and seminomatous carcinoma. Surprisingly, only one each of fallopian tube adenocarcinoma and ovarian cancer were reported.

All but eight patients in this study underwent a preliminary cystoscopy with the intention to document the obstruction with a retrograde pyelography followed by an attempt to bypass the obstruction. In only 11 cases (15.2%) were retrograde stenting successful. The cystoscopic findings of these patients included: non-identifiable and displaced ureteral orifices and tumor-invaded orifices. Percutaneous nephrostomy was attempted following failure of retrograde stenting and was successful in 55 (76%). In this institute, this procedure has been safely performed under ultrasonographic and fluoroscopic guidance, under local or general anesthesia. As a whole, this procedure has been widely used because of improved percutaneous techniques and better imaging. It is therefore associated with very few significant immediate complications and negligible mortality rate.^{2, 5, 18, 19, 24} The percutaneous route could also be used to insert a stent antegradely. This was attempted and successful in only one patient. Harding and Williams¹⁰ presented a very good clinical experience with antegrade ureteral stenting involving 34 successful percutaneous antegrade stent placements from 37 attempts, performed on 25 selected patients with a history of malignant disease, in whom retrograde ureteric stenting was difficult or impossible. This technique, whenever possible, is definitely more superior to percutaneous nephrostomy where care of the tube is often bothersome to the patient.

Surgical urinary diversion in the form of open DJ insertion or open nephrostomy is now seldom indicated because of improved percutaneous techniques. Open DJ insertion was done in one case of breast carcinoma after ureteral exploration for stone disease. No stone was identified and the lysis of periureteral adhesions was done. This was later attributed to metastatic disease. Open nephrostomy was done in a solitary kidney in order to avoid the possible complications of the percutaneous route, which included failure to attain an access and bleeding. Other operative diversions done such as the ileal conduit and ureterosigmoidostomy are procedures, which were necessary in order to obviate troublesome hematuria. Palliative diversion is still best done via the non-operative techniques because they are simpler, safer and entail less preparation on the part of the patients.

In this study, significant clinical improvement was seen in 81% of cases after diversion. Six percent were unimproved and 11 percent died. This finding ratifies other studies, which included smaller number of subjects. Pedersen¹⁸ noted clinical improvement in 14 out of 21 patients with ureteral occlusions secondary to advanced gynecologic malignancy. The study of Hippolite¹¹ of 41 patients underscored the improvement of renal function with percutaneous nephrostomy tubes in advanced malignancy. At the same time, he emphasized on its superiority compared to intraureteral stents in terms of lower complication rates. These confirm the concept that urinary diversion secondary to metastatic disease could easily be obviated with rapid restoration of renal function and evasion of the complications of uraemia.

Whether percutaneous nephrostomy is more superior to double-J stenting cannot be accurately determined based on our data. A more ideal design for this is a prospective randomized study with similar stage for each malignancy. Although percutaneous nephrostomies were more successful than retrograde stenting in our group, we still suggest routine cystoscopy with planned retrograde pyelography in all patients as an initial step in confirming the suspicion of the malignant nature of the obstruction. Biopsy of suspicious lesions could then be done to document tumor invasion into the bladder or ureteral orifices.

No study have yet been written stating that retrograde pyelography could be removed as part of the initial armamentarium of the urologist prior to percutaneous access.

Non-surgical means to palliate malignant ureteral obstruction have been proposed. Preliminary reports claim that early use of corticosteroids in the acute phase of bilateral ureteral obstruction and renal failure has avoided the need for nephrostomies.^{3, 9, 23}

Eleven percent of patients died despite successful urinary diversion and dialysis support. These were mostly secondary to far-advanced metastatic disease, followed by septicemia and pulmonary congestion. Whether this group of patients is best left undiverted remains to be seen. Many authors are skeptical in diverting patients with malignant ureteral obstruction because no clinical criteria exist to say which group of patients will benefit from the intervention and the reported mean survival rates of patients with advanced malignancy are low. Lau¹² studied 77 patients undergoing percutaneous nephrostomies and their survival. He classified the patients according to the nature of their obstructing lesions and the potential for further treatment. He suggested that palliative diversion be carried out only after a reasonable expectation of prolonged survival is judged to be feasible. Watkinson²⁴ proposed a protocol for selection of patients with advanced abdominopelvic malignancy most likely to benefit from nephrostomy. The results suggest that a strict selection criterion should be applied. No worthwhile benefit could be obtained from nephrostomy in the absence of adjunctive or definitive treatment for the malignancy.

The complications reported in our institute are very similar to the ones reported in literature. Dislodgment, kinking, blockade and infection form nephrostomy tubes and failed reinsertion of double-J have all been reported but the complication rate in our clinical experience is low compared to that of other authors (table 7). Lau¹² reported a complication rate as high as 24.5% for percutaneous nephrostomy and 18.5% for retrograde stenting. Desportes⁵ reported complications such as ineffective drainage (12.5%) and infection (10.5%). Urosepsis and prolonged ileus encountered after palliative cystectomy with ileal conduit or ureterosigmoidostomy are common complications encountered in prolonged intraabdominal surgery.

In summary, we report a large number of cases of malignant or metastatic ureteral obstruction, their pathology, the various clinical diversions used and their clinical outcome. We believe that palliative diversion can be safely and effectively performed in this group of patients. When appropriately applied in these patients with advanced disease, urinary diversions are useful in improving renal function and avoiding the complications of uraemia.

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