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Carcinoma of the Ureter
THE .JOURKAL OF UROLOGY
Vol. 08, No. 3, Septernb:r 1952 Printed in U.S.A. '
CARCINOMA OF THE URETER ALBERT A. CREECY
Despite the fact that since March 1948, sixteen papers relating to carcinoma of the ureter have been published in the Journal of Urology, additional data on this rare lesion seem warranted. W. vV. Scott, Long and O'Conor have emphasized the need for more information as regards treatment and results. Renner found 3 ureteral tumors in 13,854 autopsies; Jaffe and Mendillo reported only 2 cases in 90,000 routine hospital admissions; and Colston listed 2 cases of primary carcinoma of the ureter in a total of 22,000 urological cases. Long in 1948 brought the number of cases reported up to 201, since which time at least 15 additional cases have been added bringing the present number to 216. The group to be cited here consists of 7 cases of primary carcinoma of the ureter and 1 case of metastatic carcinoma of the ureter from a lesion in the prostate gland. The first patient in the group was seen in 1931 and the remaining seven have been seen since 1947. This is in comparative ratio with the fact that two-thirds of the cases of carcinoma of the ureter have been reported in the last decade and tempts one to wonder if the increase is entirely due to better diagnostic acumen, increasing longevity or possibly an increased exposure to exogenous carcinogens, as was hazarded by Davis in 1943. According to Hamm and LaValle, ureteral tumors occur most frequently in the sixth and seventh decade and the average age is 55 years. They predominate in men in the ratio of tvvo to one and the right ureter is involved more frequently than the left with 75 per cent of the lesions appearing in the lower third. In this series of 8 cases six occurred in men and two in women; 6 cases were in the eighth decade, one in the seventh and one in the sixth. Hematuria, pain and a mass in the flank or back were the most common symptoms occurring numerically in the order mentioned with the first two being present in almost all cases. Diagnosis is made from the history, physical examination, laboratory findings, cystoscopy, and pyelogram. At cystoscopy blood may be seen emerging from the orifice on the affected side and if a papillary projection is present, then the correct diagnosis is almost assured. Obstruction to the passage of a catheter in the very lowest part of the ureter may be encountered and if on injection of opaque medium under some pressure a film is obtained showing irregular dissemination then a tumor mass may be suspected. Vaginal examination in women and rectal examination in men will also be of value in diagnosing lesions in the terminal ureter. If the catheter meets a soft or mushy obstruction higher up this may help differentiate tumor from stone. A pyelo-ureterogram is most helpful giving the characteristic goblet-shaped obstruction or ring shadow, as Crance calls it, and hydro-ureter and hydronephrosis above with diminution in function. The most disturbing differential diagnosis to make is that of a small or nonopaque calculus, and in view of the radical surgery required for tumor of the ureter an error Presidential address read at annual meeting, Mid-Atlantic Section, American Urological Association, Old Point Comfort, Va., April 14, 1951.
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in this regard would be most distressing. Use of the wax bulb and study of smears by experienced pathologists using the Papanicolaou method should be of diagnostic aid. Ureteral tumors tend to multiplicity and recurrence, and these facts have stimulated many authors to advance explanations for this behavior. Von Brunn's description of the downward proliferation of the basal epithelial layer to form cell buds and nests has led Bothe to think that some carcinogen activating these areas may account for these characteristics. On the other hand, Fagerstrom questions Von Brunn's theory as to the mechanism of the formation of cell nests believing that they are abnormal patterns resulting from hyperplasia of the epithelium which in turn may be due to local irritation such as chronic infection or from noxious agents circulating in the body fluids. Gualtieri, Hayes and Segal accept Von Brunn's cell nests as the basic nuclei from which ureteral lesions develop and believe that it substantiates Ewing's hypothesis of the multicentric origin of these tumors. They believe that in addition to an abnormal urothelium, sensitization by general and local factors, a catalyst carcinogen, lytic enzyme action, numerous chemicobiological actions, growth directions and epithelial changes are also contributing factors in the developing of ureteral tumors. Kirwin believes an infectious agent in the form of a filterable virus may be the activating cause. Recurrence by lymphatic extension and by direct implantation must be recognized as potential factors. The presence of a carcinogen in the activation of ureteral lesions is accepted by many, and its most likely source would seem to be in the excretory product of the kidney. If this be true two facts remain to be explained: One is that the condition is usually unilateral indicating that only one kidney is excreting carcinogen; the other is that even after removal of a kidney with a large portion of ureter, tumor formation will recur in the stump. W.W. Scott, in reporting a case of recurring bladder papillomatosis arrested by nephro-ureterectomy and partial cystectomy for carcinoma of the ureter, offers as an explanation the possibility of a unilateral excretion of carcinogenic agent from one kidney due to alteration of the filtration tl11,eshold from some general systemic force or functional change. Once the diagnosis is made it seems generally agreed that the best treatment is complete nephro-ureterectomy removing a cuff of the bladder wall in a one stage operation. If the bladder wall around the orifice is not removed it should be desiccated after the method of Colston. If the patient's condition does not permit doing the operation in one stage, then the tumor-bearing portion shou.ld be removed first and the second part done as soon thereafter as possible. This adds increased possibility of recurrence as the stump of the ureter harbors a restless urothelium with chronic inflammation and lymphocytic infiltration which can become malignant and spread rapidly. The subject of benign tumors poses a difficult problem in diagnosis and treatment. A fortunate trend in urology has been conservation of renal tissue but when applied in lesions of the ureter it is attended with considerable hazard. Vest has presented a very valuable study in this regard on seventy odd cases of benign tumor of the ureter citing three of his own in which he elected to do conservative surgery. He states that treatment
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of ureteral tumors should be governed by the type of tumor with which one is dealing and this of course usually requires biopsy. His position has been questioned, but not justly so because he takes great care in stating his criteria for selecting cases, and if these are followed one can hardly make a mistake. Furthermore, he has emphasized that carcinoma of the ureter is a deadly serious disease and one in "Which early diagnosis with radical removal of the kidney, ureter and a portion of the bladder offers the only hope of cure and that it would be fatal to err on the side of conservatism when dealing with cases of questionable malignancy. In the cases he treated conservatively good function on the affected side was necessary, biopsy showed benign tumor and in all 3 cases reported there was impairment of total renal function and definite necessity for renal salvage. Edelstein and l\!Iarcus have also advocated conservative surgery in dealing with connective tissue tumors such as lipomas, fibromas, myomas, but in their report of 1 case which they state was a benign papilloma of the ureter they wisely elected to do nephro-ureterectomy and the patient was alive and well 15 months after surgery. A majority of tumors of the ureter are highly malignant and there is a growing trend to regard and classify the benign papilloma as an early papillary carcinoma. Because of its multiplicity, frequency of recurrence and tendency to malignant degeneration, some urologists and pathologists believe that a benign papilloma of the ureter is as rare as a benign skunk. The prognosis for survival over 2 years is poor according to Burford, Glenn and Burford. One reason for this is anatomical, due to the thin wall and rich blood and lymphatic supply of the ureter which favors early metastasis. Lowsley and Kirwin state that even in favorable cases the outlook is bad. Counseller, Cook and Seefeld reported 18 cases and of six treated by complete nephro-ureterectomy, four were dead within 3 years. The postoperative mortality is high being 24 per cent according to Stang and Hertzog, and about 25 per cent according to Long. One of the most encouraging reports is that of O'Conor who did complete nephro-ureterectomy in 8 cases and had six alive at 11, 9, 8, 7, 5, and 2 years after operation. Another lived IO years dying of a stroke and in the eighth case the patient died 3 years after operation of metastasis. The follow-up of cases along this line is constructive and answers a plea first made by W. W. Scott and later by Long for this type of report. CASE REPORTS
Case 1.-J. S. R., a white man, aged 71 years, was first seen in December 1931, with a history of hematuria of 2 weeks' duration without pain or frequency. Physical examination was negative except for early benign hypertrophy of the prostate. The urine was grossly bloody. Cystoscopy revealed no evidence of tumor in the bladder, and both ureteral meati appeared normal although a catheter could be introduced a short distance up the right side. A catheter passed normally to the left renal pelvis; the pyelogram on that side was normal whereas medium injected into the right catheter showed no dye in the right urinary tract but a diffuse irregular distribution of dye in the lower right ureter
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flowing back into the bladder. Excretory urography showed a normal left kidney. Thirty minutes after injection the right kidney pelvis and calyces were markedly dilated but the right ureter did not fill. The conclusion was that the case was one of benign hypertrophy of the prostate, and a tumor of the right ureter. Operation was refused. The patient returned May 1933, complaining of recurring attacks of right renal pain. He had passed very little blood until the last 2 weeks. Physical examination showed a well preserved man of 73 years of age. The lungs and heart were normal. The blood pressure was 155/80. No enlargement of liver or kidneys ·was present. Early hypertrophy of the prostate was noted. On rectal examination a hard, fixed tender mass was felt on the right side above the prostate. The blood count showed no anemia and the nonprotein nitrogen was normal. Again at cystoscopy the left kidney was normal but the right ureter was obstructed just above the orifice. A diagnosis of right hydronephrosis, due to tumor of the ureter was made and nephro-ureterectomy recommended. The right kidney and ureter were removed but the terminal ureter was fixed, the tumor mass invading the surrounding structures and could not be removed. The patient made a smooth recovery and the gross hematuria subsided. He was discharged in May 1933, and progressively went downhill dying of metastatic carcinoma August 1933, about 18 months after the first admission. Autopsy showed metastases to the liver, retroperitoneal lymph nodes and to the urinary bladder. The right ureter was absent to a point 4 cm. above the brim of the pelvis. It passed into a large tumor mass that measured 12 cm. in diameter. When the tumor mass was removed erosion of the ilium, sacrum and the last lumbar vertebra was noted and the common iliac artery was completely surrounded. Study of sections of the tumor showed it to be made up of atypical epithelial cells which appeared to be transitional squamous cell in type, as occurs in the ureter. They varied in size and shape and showed many mitotic figures (fig. 1).
Case 2.-The case of Mrs. B. M. aged 70 years is reported next because of some similarity to the preceding case. She was referred by Dr. vV . .J. Sturgis, .Jr . .January 11, 1950, and complained of pain in the left flank. She had also noticed blood in her urine but this was not profuse. She had some dysuria and frequency. On physical examination no masses could be palpated, although on pelvic examination some induration and tenderness were noted in the region of the left ureter. Cystoscopy disclosed that the bladder mucosa was normal. Emerging from the left ureteral orifice was a small blood clot forming a cast of the ureter. Catheters passed into the left ureteral orifice were obstructed at 2 cm. A Woodruff bulb catheter was then introduced and skiodan injected with some pressure. The dye did not enter the upper ureter but returned into the bladder and extravasated into an irregular mass in the lower ureter. Previous excretory urography and cystoscopy showed good function and a normal right kidney. A diagnosis of carcinoma of the left ureter was made and the patient was returned to Dr. W . .J. Sturgis, .Jr. who did a complete nephro-ureterectomy
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(fig. 2). Microscopic sections revealed a highly malignant, grade 4 transitional cell carcinoma of the ureter which tended to be invasive in character, (fig. 3).
Fm. 1
Fm. 2
In spite of this the patient has made a good recovery and is in good health lG months after operation.
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Both of these patients had carcinoma of the extreme lower ureter with similar symptoms and cystoscopic findings. One was seen in 1931, the other in 1950. The prompt diagnosis and the patient's acceptance of early surgical intervention in the second case has resulted in alleviation of pain and bleeding and with a reasonable hope of increasing her life expectancy. Case 3.-l\!Irs. E. H., aged 51 years, was admitted to the hospital September 18, 1949, with pain in the left flank and abdomen of 5 days' duration. She was treated at home by her family physician who gave opiates for relief and then sent her to the hospital. She had had some dysuria and frequency with hematuria once, but on admission to the hospital urinalysis was negative for blood and pus. Physical examination revealed a hypertension of 220/110 with a systolic
Fm. 3
murmur over the entire precordium. The abdomen was obese. She had pain on pressure over the left lower quadrant. No enlargement of either kidney was detected. On cystoscopy, the right ureter and kidney were entirely normal, but an obstruction was met in the left ureter at 15 cm. which could not be passed. Injection of dye through the catheter revealed a block in the left ureter giving a goblet shaped appearance with no dye in the pelvis. Excretory urography revealed good concentration with normal pelvis on the right side. There was marked hydronephrosis on the left but the ureter did not fill. A diagnosis of tumor of the ureter was made. At operation 5 days after admission the left kidney was exposed and the ureter traced down to the pelvic brim where a nodule was palpated. The ureter was mobilized well below this point, clamped and ligated. The kidney and ureter were removed in the usual manner. On opening the ureter after removal the tumor was sessile in appearance, seemed
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to be well circumscribed, and measured ½ cm. in diameter. The distal portion was not removed (fig. 4). The gross specimen consisted of a kidney 11 cm. from pole to pole. The pelvis and calyces were dilated. The attached ureter measured 14 cm. in length. A tumor mass was seen at the lower end which was whitish in color and firm in consistency. The ureter above was dilated and the ureter below was normal. Sections of the tumor mass showed it to be made of atypical cells of the transitional squamous type which varied in size and shape with many mitotic figures noted. The ureter above and below showed a marked infiltration of lymphocytes. Diagnosis: squamous cell carcinoma of the ureter. (According to :iVIelicow, infiltrating malignancies may present a squamous cell metaplasia.)
Fm. 4
The patient made an uneventful recovery and was discharged. Five months later she returned complaining of pain in the incision, left lower abdomen and radiating down the left thigh to the knee. She had lost weight. The blood pressure ,vas 150/100. The abdomen was still obese but a mass could be palpated in the left midquadrant which was quite tender. Urinalysis was negative and there was no evidence of metastasis in the lungs or osseous system. X-ray therapy was given and the mass regressed slightly but the patient's general appearance was one of beginning cachexia. She returned 6 weeks later obviously much weaker with the mass increasing in size. She died at home 8 months after the initial onset of symptoms. In this case the diagnosis was made early, treatment instituted promptly, and the lesion was quite small. However, it is believed that if a complete nephro-
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ureterectomy had been performed, the patient would have had a better chance for cure. This is particularly emphasized by the fact that recurrences are usually found in the remaining stump of the ureter or in the adjacent bladder tissue if not removed or desiccated, and as O'Conor has emphasized, these secondary lesions are often more extensive than the primary one. They also seem to develop a more malignant potential, invading adjacent tissues as though they were ideal culture media. Indeed, Bunge and Stein have found that transitional cell carcinoma of the ureter is a most favorable tumor to grow in vitro; they are study- , ing the biochemical dynamics of tumor growth in the belief that respiratory studies, the use of various hormones in the medium, the assimilation of radio isotopes and use of folic acid antagonists offer new possibilities in experimental work on cancer. Research in this field is most welcome and may add to our knowledge facts which will help support or disprove the studies on pathogenesis and etiology which have been so ably advanced by Bothe, Fagerstrom, Gualtieri, Hayes, Segal and Kirwin. This case is a good example of the necessity for doing a complete nephro-ureterectomy and an argument against conservative surgery, especially opening the ureter and taking a biopsy, as it is almost impossible to do so without danger of spilling or implanting some of these highly malignant cells before operation is completed.
Case 4.~Mr. R. T. W., aged 70 years, was admitted to the hospital March 7, 1950. The case is reported through the courtesy of Dr. W. J. Sturgis, Jr. One sister had died of carcinoma of the ureter. Two and a half years prior to admission the patient first had bloody urine unaccompanied by any other symptoms. Six weeks previous to admission a pain developed in the small of the back and 2 days later the patient noticed murky urine. The hematuria had apparently always been relieved by medicine given by his family physician. On physical examination the patient was a well preserved white man. The blood pressure was 190/100. The cardiac rhythm was abnormal with extrasystoles. The prostate was enlarged about 2 plus, but was neither hard nor nodular. Excretory urography revealed a nonfunctioning left kidney and a normal upper right urinary tract. Retrograde pyelography showed dilated minor calyces at the upper pole of the left kidney and a bulbous lower half left kidney with no calyx extending into it. At operation on March 15 a complete nephro-ureterectomy was done. The postoperative course was gradually downhill characterized primarily by abdominal distention which persisted despite efforts to decompress the gastro-intestinal tract by intubation. The nonprotein nitrogen was 88.8 three days prior to death, which occurred 11 days after operation. Examination of the specimen revealed a tumor at the ureteropelvic junction. Microscopic study of the sections disclosed carcinoma and showed much the same architecture as papilloma of the ureter with malignant changes. Final diagnosis: Papillary carcinoma, ureter, left. Case 5.~Mr. T. L., aged 70 years, was admitted to the hospital in May 1948, complaining of blood in the urine. The present episode started 1 week prior to
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admission. He had no pain. He had frequency about 4 times each night. He gave a history of hematuria 1 year previously. This disappeared following treatment by his family physician only to recur 6 months later. On physical examination patches of psoriasis were seen on his knees and elbows. Excretory urography showed that the left kidney was normal in function, drainage, and appearance. The right kidney function was impaired. On cystoscopic examination an obstruction was met in the right ureter at 9 cm. Retrograde pyelogram showed an irregular filling in the midportion of the right ureter suggestive of a spacetaking lesion. Dilatation of the proximal ureter and marked hydronephrosis of the right kidney were present. Urinalysis showed 2 plus albumin and 6 to 8 red blood cells. The nonprotein nitrogen was 65 before operation, and 67 on the day of death. The blood pressure was 220/110. Nephro-ureterectomy was done on June 3, 1948. The immediate postoperative result was good. The patient was allowed out of bed, but on the second postoperative day lapsed into coma and died suddenly. A necropsy was done. Examination of the surgical specimen revealed the upper 16 cm. of the ureter greatly distended. There was a firm, bulbous swelling in the distal 4 cm. On opening the ureter the upper portion was about 3 cm. in circumference. The swelling was due to multiple, soft, white polypoid masses with a broad, sessile, infiltrating base extending for about 4 cm. up the ureter. A projecting tongue extended down to a point of constriction. Section of the ureter revealed that the tumor extended into and infiltrated the mucosa. Microscopic section of the ureter adjacent to the tumor showed tremendous heaping of the transitional epithelium and as one approached the tumor it became definitely papillary in type but was composed of closely packed papillae. There was, however, no invasion of the muscularis. The stroma was scant and mitoses were rare. Perivascular round cell infiltration was also manifest in the surrounding fat. Diagnosis: Papillary carcinoma ureter, grade 2.
Case 6.-Mr. S. M., aged 64 years, was admitted to the hospital April 28, 1949 with a chief complaint of backache. He had had backache for several weeks and was unable to work. He had lost weight. No hematuria was present, but he had some frequency. Physical examination showed loss of weight. Bronchial rales were present throughout the chest. The heart was slightly enlarged to the left. The prostate was slightly enlarged and indurated. The blood pressure was 130/76. Cystoscopy revealed a small papilloma on the right lateral wall of the bladder just above the meatus. A catheter passed easily to the right kidney pelvis, but an obstruction was met in the midureter on the left. A retrograde pyelogram revealed a normal pelvis on the right but pyelogram of the left kidney showed hydronephrosis with a filling defect in the middle third of the left ureter. A papilloma of the bladder was destroyed by fulguration. Biopsy of the tumor revealed papillary fragments with little stroma and quite cellular. Few mitotic figures were seen. One week later a left nephro-ureterectomy was done. Pathological examination of the surgical specimen showed that the pelvis and calyces were distended and filled with thick purulent material. On opening the ureter
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the lower 3 cm. was occupied by a sessile tumor mass which had some papillary arrangement. Microscopic study showed a papillary tumor in the ureter with anaplastic cells containing large irregular nuclei, mitoses, cell atypism and marked invasion of the lymphatics in the wall of the ureter. Tumor tissue was even found in the adherent blood clot. Final diagnosis: Ureter, papillary carcinoma, grade 4. Prompt recurrence was to be anticipated. Four months after operation the patient died and autopsy showed metastases to the liver. Case 7.~Mr. W. L. T. was admitted to the hospital July 27, 1948 complaining of weakness in the left arm and left leg. A jacksonian type of epilepsy developed followed by confusion and headaches. It was believed that this patient had a brain tumor, but an operation was not performed due to his advanced age and poor condition. He gradually became comatose and died quietly 1 month after admission. Laboratory examination revealed a few red blood cells, granular casts and many pus cells in urinalyses while he was in the hospital. Necropsy revealed a squamous cell carcinoma of the lung with metastasis to the brain. An incidental finding at the post-mortem examination was a small papillary carcinoma of the right ureter. It was located at the distal third of the right ureter and measured approximately l½ by 1 cm. in diameter. Grossly, it appeared to have originated from the mucosa of the ureter. However, there was no obstruction or dilatation of the ureter proximal to this tumor. Microscopic examination showed atypical delicate papillary structure with a scant stroma, a narrow pedicle and no invasion of the stroma. No urograms were taken on this patient. Case 8.~E. C. K., aged 73 years, a white man, was admitted to the hospital on May 19, 1949 complaining of pain in the right kidney. He had suffered constant pain 1 week prior to admission. Had passed no stones or blood. Pain radiated across the lower abdomen. He had had nocturia 2 to 5 times for 3 years. On examination the blood pressure was 160/114. The patient had tenderness in the upper portion of the right ureter. The prostate gland was hard, fixed and nodular. An excretory urogram was unsatisfactory. A retrograde pyelogram showed the left ureter and kidney to be normal. On the right there was a moderate degree of calyectesis and hydronephrosis. There was moderate dilatation of the'proximal two-thirds of the right ureter with marked narrowing at the junction of the middle and distal thirds. It was thought that the patient had a stricture of the ureter with hydronephrosis of the right kidney. Gallbladder studies revealed cholecystitis and cholelithiasis. An x-ray revealed osteosclerosis of the bone in the region of the acetabulum and superior ramus in the pubis on the left. Similar changes were present in the ilium just above the acetabulum as well as in the left lumbosacral articulation. These changes were compatible with metastatic prostatic carcinoma. Laboratory findings: nonprotein nitrogen 27, serum acid phosphatase 6.2 units, cephalin flocculation 2 plus. Because of intractable renal colic, a right nephro-ureterectomy was done. Convalescence
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was uneventful. The patient was placed on stilbestrol 5 mg. daily. The surgical specimen consisted of a kidney 11 by 6 by 4 cm. with 12 cm. of ureter attached. The pelvis and ureter were slightly dilated. The distal end of the ureter showed some thickening of the wall and the lumen was narrowed at this point. Sections of the ureter showed infiltration of the surrounding tissue particularly the perivascular lymphatics with glandular tissue composed of small tubules with pale cuboidal cells resembling prostatic cells. There was no mitosis and very little cell atypism. The nuclei were large, vesicular and had a prominent nucleolus. The ureteral mucosa was intact in the specimen removed. Impression: Metastatic carcinoma of the ureter suggestive of primary carcinoma of the prostate. The patient was living 23 months after operation. He was still on stilbestrol therapy. True, metastatic carcinoma of the ureter is rare. Thirty-five cases were collected by Presman and Ehrlich in March 1948, to which they added 2 cases of their own. By true metastatic carcinoma is meant carcinoma that invades the ureter by the lymphatics and blood vessels from a lesion elsewhere in the body and has not invaded by direct extension from a lesion such as carcinoma of the renal pelvis or bladder. In one of the cases reported by Presman and Ehrlich, the primary lesion was in the lung and the other was in the stomach. Of the 37 cases reported, eight were from the prostate, eight from the stomach, four from generalized lymphoma, three from the cervix and two each from the bladder, breast, lung, colon, and ovary. Lazarus states that the criteria for true metastases to the ureter are the establishment of a primary lesion elsewhere, the cells in the primary lesion and the metastatic lesion must be similar and that these cells can be demonstrated microscopically in the perivascular lymphatics or blood vessels of the ureteral wall. In 1941, he reported 18 cases, seven of which originated in the prostate. It would seem that the case cited here is a true metastatic carcinoma of the ureter originating in the prostate, based on the clinical laboratory and x-ray findings in conjunction with the pathological description of cells resembling prostatic carcinoma invading the perivascular lymphatics SUMMARY
Eight additional cases of carcinoma of the ureter have been reported. Seven of these were primary carcinoma of the ureter, one of which was found at autopsy. The remaining case was metastatic from the prostate gland. Six of the cases of primary carcinoma came to operation, partial nephro-ureterectomy being done in three, all of whom died within 1 year. Three patients all 70 years of age or over had complete nephro-ureterectomy; one was alive and well 16 months after operation and 2 died postoperatively within 48 hours. The patient who had metastatic carcinoma from the prostate underwent partial nephroureterectomy and was alive 2 years after operation. From these facts it is evident that carcinoma of the ureter is being seen more commonly than in the past, that it is a very fatal disease and that the best hope for cure is complete nephro-ureterectomy despite the fact that the mortality rate, especially in the aged, is still high.
256 Blair Ave., Newport News, Va.
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REFERENCES BoTHE, A. E.: J. Urol., 53: 451, 1945. BUNGE, R. G. AND STEIN, R. J.: J. Urol., 64: 646, 1950. BURFORD, C. E., GLENN, J.E. AND BURFORD, E. H.: J. Urol., 60: 337, 1948. COLSTON, J. A. C.: Bull. Johns Hopkins Hosp., 56: 361, 1934. CouNSELLER, V. S., CooK, E. N. AND SEEFELD, P.H.: J. Urol., 51: 606, 1944. CRANCE, A. M. AND KNICKERBOCKER, H. J.: J. Urol., 64: 300, 1950. DAVIS, E.: J. Urol., 49: 14, 1943. EDELSTEIN, J.M. AND MARCUS, S. M.: J. Urol., 60: 409, 1948. EWING, J.: Neoplastic Diseases. Philadelphia: W. B. Saunders Co., 1928, 3 ed. FAGERSTROM, D. P.: J. Urol., 69: 333, 1948. GUALTIERI, T., HAYES, J. J. AND SEGAL, A. D.: J. Urol., 59: 1083, 1948. HAMM, F. C. AND LA VALLE, L. L.: J. Urol., 61: 493, 1949. JAFFE, S. A. AND MENDILLO, A. J.: Am. J. Surg., 62: 126, 1943. KIRWIN, T. J.: J. Urol., 49: 1, 1943. LAZARUS, J. A.: J. Urol., 45: 527, 1941. LONG, J. H.: J. Urol., 61: 23, 1949. LowsLEY, 0. S. AND KIRWIN, T. J.: Clinical Urology. Baltimore: Williams and Wilkins Co., 1944, 2nd ed. MELICOW, M. M.: J. Urol., 54: 186, 1945. O'CoNoR, V. J.: J. Urol., 61: 488, 1949. PRESMAN, D. AND EHRLICH, L.: J. Urol., 59: 312, 1948. RENNER, M. J.: Surg., Gynec. & Obst., 52: 793, 1931. SCOTT, W.W.: J. Urol., 50: 45, 1943. Also J. Urol., 65: 235, 1951. STANG, H. M. AND HERTZOG, A. J.: J. Urol., 45: 519, 1941. VEST, S. A.: J. Urol., 53: 97, 1945. VoN BRUNN, A.: Arch. f. mikr. Anat., 41: 294, 1893.
Vol. 08, No. 3, Septernb:r 1952 Printed in U.S.A. '
CARCINOMA OF THE URETER ALBERT A. CREECY
Despite the fact that since March 1948, sixteen papers relating to carcinoma of the ureter have been published in the Journal of Urology, additional data on this rare lesion seem warranted. W. vV. Scott, Long and O'Conor have emphasized the need for more information as regards treatment and results. Renner found 3 ureteral tumors in 13,854 autopsies; Jaffe and Mendillo reported only 2 cases in 90,000 routine hospital admissions; and Colston listed 2 cases of primary carcinoma of the ureter in a total of 22,000 urological cases. Long in 1948 brought the number of cases reported up to 201, since which time at least 15 additional cases have been added bringing the present number to 216. The group to be cited here consists of 7 cases of primary carcinoma of the ureter and 1 case of metastatic carcinoma of the ureter from a lesion in the prostate gland. The first patient in the group was seen in 1931 and the remaining seven have been seen since 1947. This is in comparative ratio with the fact that two-thirds of the cases of carcinoma of the ureter have been reported in the last decade and tempts one to wonder if the increase is entirely due to better diagnostic acumen, increasing longevity or possibly an increased exposure to exogenous carcinogens, as was hazarded by Davis in 1943. According to Hamm and LaValle, ureteral tumors occur most frequently in the sixth and seventh decade and the average age is 55 years. They predominate in men in the ratio of tvvo to one and the right ureter is involved more frequently than the left with 75 per cent of the lesions appearing in the lower third. In this series of 8 cases six occurred in men and two in women; 6 cases were in the eighth decade, one in the seventh and one in the sixth. Hematuria, pain and a mass in the flank or back were the most common symptoms occurring numerically in the order mentioned with the first two being present in almost all cases. Diagnosis is made from the history, physical examination, laboratory findings, cystoscopy, and pyelogram. At cystoscopy blood may be seen emerging from the orifice on the affected side and if a papillary projection is present, then the correct diagnosis is almost assured. Obstruction to the passage of a catheter in the very lowest part of the ureter may be encountered and if on injection of opaque medium under some pressure a film is obtained showing irregular dissemination then a tumor mass may be suspected. Vaginal examination in women and rectal examination in men will also be of value in diagnosing lesions in the terminal ureter. If the catheter meets a soft or mushy obstruction higher up this may help differentiate tumor from stone. A pyelo-ureterogram is most helpful giving the characteristic goblet-shaped obstruction or ring shadow, as Crance calls it, and hydro-ureter and hydronephrosis above with diminution in function. The most disturbing differential diagnosis to make is that of a small or nonopaque calculus, and in view of the radical surgery required for tumor of the ureter an error Presidential address read at annual meeting, Mid-Atlantic Section, American Urological Association, Old Point Comfort, Va., April 14, 1951.
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in this regard would be most distressing. Use of the wax bulb and study of smears by experienced pathologists using the Papanicolaou method should be of diagnostic aid. Ureteral tumors tend to multiplicity and recurrence, and these facts have stimulated many authors to advance explanations for this behavior. Von Brunn's description of the downward proliferation of the basal epithelial layer to form cell buds and nests has led Bothe to think that some carcinogen activating these areas may account for these characteristics. On the other hand, Fagerstrom questions Von Brunn's theory as to the mechanism of the formation of cell nests believing that they are abnormal patterns resulting from hyperplasia of the epithelium which in turn may be due to local irritation such as chronic infection or from noxious agents circulating in the body fluids. Gualtieri, Hayes and Segal accept Von Brunn's cell nests as the basic nuclei from which ureteral lesions develop and believe that it substantiates Ewing's hypothesis of the multicentric origin of these tumors. They believe that in addition to an abnormal urothelium, sensitization by general and local factors, a catalyst carcinogen, lytic enzyme action, numerous chemicobiological actions, growth directions and epithelial changes are also contributing factors in the developing of ureteral tumors. Kirwin believes an infectious agent in the form of a filterable virus may be the activating cause. Recurrence by lymphatic extension and by direct implantation must be recognized as potential factors. The presence of a carcinogen in the activation of ureteral lesions is accepted by many, and its most likely source would seem to be in the excretory product of the kidney. If this be true two facts remain to be explained: One is that the condition is usually unilateral indicating that only one kidney is excreting carcinogen; the other is that even after removal of a kidney with a large portion of ureter, tumor formation will recur in the stump. W.W. Scott, in reporting a case of recurring bladder papillomatosis arrested by nephro-ureterectomy and partial cystectomy for carcinoma of the ureter, offers as an explanation the possibility of a unilateral excretion of carcinogenic agent from one kidney due to alteration of the filtration tl11,eshold from some general systemic force or functional change. Once the diagnosis is made it seems generally agreed that the best treatment is complete nephro-ureterectomy removing a cuff of the bladder wall in a one stage operation. If the bladder wall around the orifice is not removed it should be desiccated after the method of Colston. If the patient's condition does not permit doing the operation in one stage, then the tumor-bearing portion shou.ld be removed first and the second part done as soon thereafter as possible. This adds increased possibility of recurrence as the stump of the ureter harbors a restless urothelium with chronic inflammation and lymphocytic infiltration which can become malignant and spread rapidly. The subject of benign tumors poses a difficult problem in diagnosis and treatment. A fortunate trend in urology has been conservation of renal tissue but when applied in lesions of the ureter it is attended with considerable hazard. Vest has presented a very valuable study in this regard on seventy odd cases of benign tumor of the ureter citing three of his own in which he elected to do conservative surgery. He states that treatment
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of ureteral tumors should be governed by the type of tumor with which one is dealing and this of course usually requires biopsy. His position has been questioned, but not justly so because he takes great care in stating his criteria for selecting cases, and if these are followed one can hardly make a mistake. Furthermore, he has emphasized that carcinoma of the ureter is a deadly serious disease and one in "Which early diagnosis with radical removal of the kidney, ureter and a portion of the bladder offers the only hope of cure and that it would be fatal to err on the side of conservatism when dealing with cases of questionable malignancy. In the cases he treated conservatively good function on the affected side was necessary, biopsy showed benign tumor and in all 3 cases reported there was impairment of total renal function and definite necessity for renal salvage. Edelstein and l\!Iarcus have also advocated conservative surgery in dealing with connective tissue tumors such as lipomas, fibromas, myomas, but in their report of 1 case which they state was a benign papilloma of the ureter they wisely elected to do nephro-ureterectomy and the patient was alive and well 15 months after surgery. A majority of tumors of the ureter are highly malignant and there is a growing trend to regard and classify the benign papilloma as an early papillary carcinoma. Because of its multiplicity, frequency of recurrence and tendency to malignant degeneration, some urologists and pathologists believe that a benign papilloma of the ureter is as rare as a benign skunk. The prognosis for survival over 2 years is poor according to Burford, Glenn and Burford. One reason for this is anatomical, due to the thin wall and rich blood and lymphatic supply of the ureter which favors early metastasis. Lowsley and Kirwin state that even in favorable cases the outlook is bad. Counseller, Cook and Seefeld reported 18 cases and of six treated by complete nephro-ureterectomy, four were dead within 3 years. The postoperative mortality is high being 24 per cent according to Stang and Hertzog, and about 25 per cent according to Long. One of the most encouraging reports is that of O'Conor who did complete nephro-ureterectomy in 8 cases and had six alive at 11, 9, 8, 7, 5, and 2 years after operation. Another lived IO years dying of a stroke and in the eighth case the patient died 3 years after operation of metastasis. The follow-up of cases along this line is constructive and answers a plea first made by W. W. Scott and later by Long for this type of report. CASE REPORTS
Case 1.-J. S. R., a white man, aged 71 years, was first seen in December 1931, with a history of hematuria of 2 weeks' duration without pain or frequency. Physical examination was negative except for early benign hypertrophy of the prostate. The urine was grossly bloody. Cystoscopy revealed no evidence of tumor in the bladder, and both ureteral meati appeared normal although a catheter could be introduced a short distance up the right side. A catheter passed normally to the left renal pelvis; the pyelogram on that side was normal whereas medium injected into the right catheter showed no dye in the right urinary tract but a diffuse irregular distribution of dye in the lower right ureter
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flowing back into the bladder. Excretory urography showed a normal left kidney. Thirty minutes after injection the right kidney pelvis and calyces were markedly dilated but the right ureter did not fill. The conclusion was that the case was one of benign hypertrophy of the prostate, and a tumor of the right ureter. Operation was refused. The patient returned May 1933, complaining of recurring attacks of right renal pain. He had passed very little blood until the last 2 weeks. Physical examination showed a well preserved man of 73 years of age. The lungs and heart were normal. The blood pressure was 155/80. No enlargement of liver or kidneys ·was present. Early hypertrophy of the prostate was noted. On rectal examination a hard, fixed tender mass was felt on the right side above the prostate. The blood count showed no anemia and the nonprotein nitrogen was normal. Again at cystoscopy the left kidney was normal but the right ureter was obstructed just above the orifice. A diagnosis of right hydronephrosis, due to tumor of the ureter was made and nephro-ureterectomy recommended. The right kidney and ureter were removed but the terminal ureter was fixed, the tumor mass invading the surrounding structures and could not be removed. The patient made a smooth recovery and the gross hematuria subsided. He was discharged in May 1933, and progressively went downhill dying of metastatic carcinoma August 1933, about 18 months after the first admission. Autopsy showed metastases to the liver, retroperitoneal lymph nodes and to the urinary bladder. The right ureter was absent to a point 4 cm. above the brim of the pelvis. It passed into a large tumor mass that measured 12 cm. in diameter. When the tumor mass was removed erosion of the ilium, sacrum and the last lumbar vertebra was noted and the common iliac artery was completely surrounded. Study of sections of the tumor showed it to be made up of atypical epithelial cells which appeared to be transitional squamous cell in type, as occurs in the ureter. They varied in size and shape and showed many mitotic figures (fig. 1).
Case 2.-The case of Mrs. B. M. aged 70 years is reported next because of some similarity to the preceding case. She was referred by Dr. vV . .J. Sturgis, .Jr . .January 11, 1950, and complained of pain in the left flank. She had also noticed blood in her urine but this was not profuse. She had some dysuria and frequency. On physical examination no masses could be palpated, although on pelvic examination some induration and tenderness were noted in the region of the left ureter. Cystoscopy disclosed that the bladder mucosa was normal. Emerging from the left ureteral orifice was a small blood clot forming a cast of the ureter. Catheters passed into the left ureteral orifice were obstructed at 2 cm. A Woodruff bulb catheter was then introduced and skiodan injected with some pressure. The dye did not enter the upper ureter but returned into the bladder and extravasated into an irregular mass in the lower ureter. Previous excretory urography and cystoscopy showed good function and a normal right kidney. A diagnosis of carcinoma of the left ureter was made and the patient was returned to Dr. W . .J. Sturgis, .Jr. who did a complete nephro-ureterectomy
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(fig. 2). Microscopic sections revealed a highly malignant, grade 4 transitional cell carcinoma of the ureter which tended to be invasive in character, (fig. 3).
Fm. 1
Fm. 2
In spite of this the patient has made a good recovery and is in good health lG months after operation.
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Both of these patients had carcinoma of the extreme lower ureter with similar symptoms and cystoscopic findings. One was seen in 1931, the other in 1950. The prompt diagnosis and the patient's acceptance of early surgical intervention in the second case has resulted in alleviation of pain and bleeding and with a reasonable hope of increasing her life expectancy. Case 3.-l\!Irs. E. H., aged 51 years, was admitted to the hospital September 18, 1949, with pain in the left flank and abdomen of 5 days' duration. She was treated at home by her family physician who gave opiates for relief and then sent her to the hospital. She had had some dysuria and frequency with hematuria once, but on admission to the hospital urinalysis was negative for blood and pus. Physical examination revealed a hypertension of 220/110 with a systolic
Fm. 3
murmur over the entire precordium. The abdomen was obese. She had pain on pressure over the left lower quadrant. No enlargement of either kidney was detected. On cystoscopy, the right ureter and kidney were entirely normal, but an obstruction was met in the left ureter at 15 cm. which could not be passed. Injection of dye through the catheter revealed a block in the left ureter giving a goblet shaped appearance with no dye in the pelvis. Excretory urography revealed good concentration with normal pelvis on the right side. There was marked hydronephrosis on the left but the ureter did not fill. A diagnosis of tumor of the ureter was made. At operation 5 days after admission the left kidney was exposed and the ureter traced down to the pelvic brim where a nodule was palpated. The ureter was mobilized well below this point, clamped and ligated. The kidney and ureter were removed in the usual manner. On opening the ureter after removal the tumor was sessile in appearance, seemed
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to be well circumscribed, and measured ½ cm. in diameter. The distal portion was not removed (fig. 4). The gross specimen consisted of a kidney 11 cm. from pole to pole. The pelvis and calyces were dilated. The attached ureter measured 14 cm. in length. A tumor mass was seen at the lower end which was whitish in color and firm in consistency. The ureter above was dilated and the ureter below was normal. Sections of the tumor mass showed it to be made of atypical cells of the transitional squamous type which varied in size and shape with many mitotic figures noted. The ureter above and below showed a marked infiltration of lymphocytes. Diagnosis: squamous cell carcinoma of the ureter. (According to :iVIelicow, infiltrating malignancies may present a squamous cell metaplasia.)
Fm. 4
The patient made an uneventful recovery and was discharged. Five months later she returned complaining of pain in the incision, left lower abdomen and radiating down the left thigh to the knee. She had lost weight. The blood pressure ,vas 150/100. The abdomen was still obese but a mass could be palpated in the left midquadrant which was quite tender. Urinalysis was negative and there was no evidence of metastasis in the lungs or osseous system. X-ray therapy was given and the mass regressed slightly but the patient's general appearance was one of beginning cachexia. She returned 6 weeks later obviously much weaker with the mass increasing in size. She died at home 8 months after the initial onset of symptoms. In this case the diagnosis was made early, treatment instituted promptly, and the lesion was quite small. However, it is believed that if a complete nephro-
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ureterectomy had been performed, the patient would have had a better chance for cure. This is particularly emphasized by the fact that recurrences are usually found in the remaining stump of the ureter or in the adjacent bladder tissue if not removed or desiccated, and as O'Conor has emphasized, these secondary lesions are often more extensive than the primary one. They also seem to develop a more malignant potential, invading adjacent tissues as though they were ideal culture media. Indeed, Bunge and Stein have found that transitional cell carcinoma of the ureter is a most favorable tumor to grow in vitro; they are study- , ing the biochemical dynamics of tumor growth in the belief that respiratory studies, the use of various hormones in the medium, the assimilation of radio isotopes and use of folic acid antagonists offer new possibilities in experimental work on cancer. Research in this field is most welcome and may add to our knowledge facts which will help support or disprove the studies on pathogenesis and etiology which have been so ably advanced by Bothe, Fagerstrom, Gualtieri, Hayes, Segal and Kirwin. This case is a good example of the necessity for doing a complete nephro-ureterectomy and an argument against conservative surgery, especially opening the ureter and taking a biopsy, as it is almost impossible to do so without danger of spilling or implanting some of these highly malignant cells before operation is completed.
Case 4.~Mr. R. T. W., aged 70 years, was admitted to the hospital March 7, 1950. The case is reported through the courtesy of Dr. W. J. Sturgis, Jr. One sister had died of carcinoma of the ureter. Two and a half years prior to admission the patient first had bloody urine unaccompanied by any other symptoms. Six weeks previous to admission a pain developed in the small of the back and 2 days later the patient noticed murky urine. The hematuria had apparently always been relieved by medicine given by his family physician. On physical examination the patient was a well preserved white man. The blood pressure was 190/100. The cardiac rhythm was abnormal with extrasystoles. The prostate was enlarged about 2 plus, but was neither hard nor nodular. Excretory urography revealed a nonfunctioning left kidney and a normal upper right urinary tract. Retrograde pyelography showed dilated minor calyces at the upper pole of the left kidney and a bulbous lower half left kidney with no calyx extending into it. At operation on March 15 a complete nephro-ureterectomy was done. The postoperative course was gradually downhill characterized primarily by abdominal distention which persisted despite efforts to decompress the gastro-intestinal tract by intubation. The nonprotein nitrogen was 88.8 three days prior to death, which occurred 11 days after operation. Examination of the specimen revealed a tumor at the ureteropelvic junction. Microscopic study of the sections disclosed carcinoma and showed much the same architecture as papilloma of the ureter with malignant changes. Final diagnosis: Papillary carcinoma, ureter, left. Case 5.~Mr. T. L., aged 70 years, was admitted to the hospital in May 1948, complaining of blood in the urine. The present episode started 1 week prior to
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admission. He had no pain. He had frequency about 4 times each night. He gave a history of hematuria 1 year previously. This disappeared following treatment by his family physician only to recur 6 months later. On physical examination patches of psoriasis were seen on his knees and elbows. Excretory urography showed that the left kidney was normal in function, drainage, and appearance. The right kidney function was impaired. On cystoscopic examination an obstruction was met in the right ureter at 9 cm. Retrograde pyelogram showed an irregular filling in the midportion of the right ureter suggestive of a spacetaking lesion. Dilatation of the proximal ureter and marked hydronephrosis of the right kidney were present. Urinalysis showed 2 plus albumin and 6 to 8 red blood cells. The nonprotein nitrogen was 65 before operation, and 67 on the day of death. The blood pressure was 220/110. Nephro-ureterectomy was done on June 3, 1948. The immediate postoperative result was good. The patient was allowed out of bed, but on the second postoperative day lapsed into coma and died suddenly. A necropsy was done. Examination of the surgical specimen revealed the upper 16 cm. of the ureter greatly distended. There was a firm, bulbous swelling in the distal 4 cm. On opening the ureter the upper portion was about 3 cm. in circumference. The swelling was due to multiple, soft, white polypoid masses with a broad, sessile, infiltrating base extending for about 4 cm. up the ureter. A projecting tongue extended down to a point of constriction. Section of the ureter revealed that the tumor extended into and infiltrated the mucosa. Microscopic section of the ureter adjacent to the tumor showed tremendous heaping of the transitional epithelium and as one approached the tumor it became definitely papillary in type but was composed of closely packed papillae. There was, however, no invasion of the muscularis. The stroma was scant and mitoses were rare. Perivascular round cell infiltration was also manifest in the surrounding fat. Diagnosis: Papillary carcinoma ureter, grade 2.
Case 6.-Mr. S. M., aged 64 years, was admitted to the hospital April 28, 1949 with a chief complaint of backache. He had had backache for several weeks and was unable to work. He had lost weight. No hematuria was present, but he had some frequency. Physical examination showed loss of weight. Bronchial rales were present throughout the chest. The heart was slightly enlarged to the left. The prostate was slightly enlarged and indurated. The blood pressure was 130/76. Cystoscopy revealed a small papilloma on the right lateral wall of the bladder just above the meatus. A catheter passed easily to the right kidney pelvis, but an obstruction was met in the midureter on the left. A retrograde pyelogram revealed a normal pelvis on the right but pyelogram of the left kidney showed hydronephrosis with a filling defect in the middle third of the left ureter. A papilloma of the bladder was destroyed by fulguration. Biopsy of the tumor revealed papillary fragments with little stroma and quite cellular. Few mitotic figures were seen. One week later a left nephro-ureterectomy was done. Pathological examination of the surgical specimen showed that the pelvis and calyces were distended and filled with thick purulent material. On opening the ureter
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the lower 3 cm. was occupied by a sessile tumor mass which had some papillary arrangement. Microscopic study showed a papillary tumor in the ureter with anaplastic cells containing large irregular nuclei, mitoses, cell atypism and marked invasion of the lymphatics in the wall of the ureter. Tumor tissue was even found in the adherent blood clot. Final diagnosis: Ureter, papillary carcinoma, grade 4. Prompt recurrence was to be anticipated. Four months after operation the patient died and autopsy showed metastases to the liver. Case 7.~Mr. W. L. T. was admitted to the hospital July 27, 1948 complaining of weakness in the left arm and left leg. A jacksonian type of epilepsy developed followed by confusion and headaches. It was believed that this patient had a brain tumor, but an operation was not performed due to his advanced age and poor condition. He gradually became comatose and died quietly 1 month after admission. Laboratory examination revealed a few red blood cells, granular casts and many pus cells in urinalyses while he was in the hospital. Necropsy revealed a squamous cell carcinoma of the lung with metastasis to the brain. An incidental finding at the post-mortem examination was a small papillary carcinoma of the right ureter. It was located at the distal third of the right ureter and measured approximately l½ by 1 cm. in diameter. Grossly, it appeared to have originated from the mucosa of the ureter. However, there was no obstruction or dilatation of the ureter proximal to this tumor. Microscopic examination showed atypical delicate papillary structure with a scant stroma, a narrow pedicle and no invasion of the stroma. No urograms were taken on this patient. Case 8.~E. C. K., aged 73 years, a white man, was admitted to the hospital on May 19, 1949 complaining of pain in the right kidney. He had suffered constant pain 1 week prior to admission. Had passed no stones or blood. Pain radiated across the lower abdomen. He had had nocturia 2 to 5 times for 3 years. On examination the blood pressure was 160/114. The patient had tenderness in the upper portion of the right ureter. The prostate gland was hard, fixed and nodular. An excretory urogram was unsatisfactory. A retrograde pyelogram showed the left ureter and kidney to be normal. On the right there was a moderate degree of calyectesis and hydronephrosis. There was moderate dilatation of the'proximal two-thirds of the right ureter with marked narrowing at the junction of the middle and distal thirds. It was thought that the patient had a stricture of the ureter with hydronephrosis of the right kidney. Gallbladder studies revealed cholecystitis and cholelithiasis. An x-ray revealed osteosclerosis of the bone in the region of the acetabulum and superior ramus in the pubis on the left. Similar changes were present in the ilium just above the acetabulum as well as in the left lumbosacral articulation. These changes were compatible with metastatic prostatic carcinoma. Laboratory findings: nonprotein nitrogen 27, serum acid phosphatase 6.2 units, cephalin flocculation 2 plus. Because of intractable renal colic, a right nephro-ureterectomy was done. Convalescence
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was uneventful. The patient was placed on stilbestrol 5 mg. daily. The surgical specimen consisted of a kidney 11 by 6 by 4 cm. with 12 cm. of ureter attached. The pelvis and ureter were slightly dilated. The distal end of the ureter showed some thickening of the wall and the lumen was narrowed at this point. Sections of the ureter showed infiltration of the surrounding tissue particularly the perivascular lymphatics with glandular tissue composed of small tubules with pale cuboidal cells resembling prostatic cells. There was no mitosis and very little cell atypism. The nuclei were large, vesicular and had a prominent nucleolus. The ureteral mucosa was intact in the specimen removed. Impression: Metastatic carcinoma of the ureter suggestive of primary carcinoma of the prostate. The patient was living 23 months after operation. He was still on stilbestrol therapy. True, metastatic carcinoma of the ureter is rare. Thirty-five cases were collected by Presman and Ehrlich in March 1948, to which they added 2 cases of their own. By true metastatic carcinoma is meant carcinoma that invades the ureter by the lymphatics and blood vessels from a lesion elsewhere in the body and has not invaded by direct extension from a lesion such as carcinoma of the renal pelvis or bladder. In one of the cases reported by Presman and Ehrlich, the primary lesion was in the lung and the other was in the stomach. Of the 37 cases reported, eight were from the prostate, eight from the stomach, four from generalized lymphoma, three from the cervix and two each from the bladder, breast, lung, colon, and ovary. Lazarus states that the criteria for true metastases to the ureter are the establishment of a primary lesion elsewhere, the cells in the primary lesion and the metastatic lesion must be similar and that these cells can be demonstrated microscopically in the perivascular lymphatics or blood vessels of the ureteral wall. In 1941, he reported 18 cases, seven of which originated in the prostate. It would seem that the case cited here is a true metastatic carcinoma of the ureter originating in the prostate, based on the clinical laboratory and x-ray findings in conjunction with the pathological description of cells resembling prostatic carcinoma invading the perivascular lymphatics SUMMARY
Eight additional cases of carcinoma of the ureter have been reported. Seven of these were primary carcinoma of the ureter, one of which was found at autopsy. The remaining case was metastatic from the prostate gland. Six of the cases of primary carcinoma came to operation, partial nephro-ureterectomy being done in three, all of whom died within 1 year. Three patients all 70 years of age or over had complete nephro-ureterectomy; one was alive and well 16 months after operation and 2 died postoperatively within 48 hours. The patient who had metastatic carcinoma from the prostate underwent partial nephroureterectomy and was alive 2 years after operation. From these facts it is evident that carcinoma of the ureter is being seen more commonly than in the past, that it is a very fatal disease and that the best hope for cure is complete nephro-ureterectomy despite the fact that the mortality rate, especially in the aged, is still high.
256 Blair Ave., Newport News, Va.
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REFERENCES BoTHE, A. E.: J. Urol., 53: 451, 1945. BUNGE, R. G. AND STEIN, R. J.: J. Urol., 64: 646, 1950. BURFORD, C. E., GLENN, J.E. AND BURFORD, E. H.: J. Urol., 60: 337, 1948. COLSTON, J. A. C.: Bull. Johns Hopkins Hosp., 56: 361, 1934. CouNSELLER, V. S., CooK, E. N. AND SEEFELD, P.H.: J. Urol., 51: 606, 1944. CRANCE, A. M. AND KNICKERBOCKER, H. J.: J. Urol., 64: 300, 1950. DAVIS, E.: J. Urol., 49: 14, 1943. EDELSTEIN, J.M. AND MARCUS, S. M.: J. Urol., 60: 409, 1948. EWING, J.: Neoplastic Diseases. Philadelphia: W. B. Saunders Co., 1928, 3 ed. FAGERSTROM, D. P.: J. Urol., 69: 333, 1948. GUALTIERI, T., HAYES, J. J. AND SEGAL, A. D.: J. Urol., 59: 1083, 1948. HAMM, F. C. AND LA VALLE, L. L.: J. Urol., 61: 493, 1949. JAFFE, S. A. AND MENDILLO, A. J.: Am. J. Surg., 62: 126, 1943. KIRWIN, T. J.: J. Urol., 49: 1, 1943. LAZARUS, J. A.: J. Urol., 45: 527, 1941. LONG, J. H.: J. Urol., 61: 23, 1949. LowsLEY, 0. S. AND KIRWIN, T. J.: Clinical Urology. Baltimore: Williams and Wilkins Co., 1944, 2nd ed. MELICOW, M. M.: J. Urol., 54: 186, 1945. O'CoNoR, V. J.: J. Urol., 61: 488, 1949. PRESMAN, D. AND EHRLICH, L.: J. Urol., 59: 312, 1948. RENNER, M. J.: Surg., Gynec. & Obst., 52: 793, 1931. SCOTT, W.W.: J. Urol., 50: 45, 1943. Also J. Urol., 65: 235, 1951. STANG, H. M. AND HERTZOG, A. J.: J. Urol., 45: 519, 1941. VEST, S. A.: J. Urol., 53: 97, 1945. VoN BRUNN, A.: Arch. f. mikr. Anat., 41: 294, 1893.