renal cell carcinoma in the solitary kidney: report of six cases
TRANSCRIPT
RENAL CELL CARCINOMA IN THE SOLITARY KIDNEY: REPORT OF SIX CASES1
By JOSEPH J. KAUFMAN, M.D., BEN T. CHAFFEY, M.D. and WILLARD E. GOODWIN, M.D.
From the University of California, Los Angeles School of Medicine, Department of Surgery1 Urology, Los Angeles, California 90024, and Wadsworth Hospital, Veterans Administration Center,
Los Angeles, California
TWENTY-ONE cases of renal cell carcinoma in a solitary kidney have appeared in the literature. Six additional cases are being reported. The chief interest of these tumours lies in their un- predictable biological behaviour which sometimes impels the urologist to exert unorthodox methods of surgical attack
CASE REPORTS Case 1.-G. H., U.C.L.A. No. 011-63-23, a 52-year-old Caucasian man, had intermittent hamaturia for 18
months. When blood first appeared investigation suggested congenital absence of the left kidney and an enlarged right kidney. A kidney needle biopsy was performed by the referring urologist and this showed hypernephroma. The patient had lost 15 lb. in weight. There were no pathological findings in the chest, but in the right upper abdomen there was a slightly tender and movable round mass.
Urinalysis showed two to three red blood cells per high-powered field; the sedimentation rate was 32 mm. per hour. P.S.P. in 30 minutes was 35 per cent.
An arteriogram confirmed absence of the left kidney and in the lower half of the right kidney the architecture was distorted by a mass which was not richly vascularised and which failed to show " tumour laking ". Skeletal survey showed no metastases. A retrograde pyelogram disclosed distortion of the right calyceal system by a mass occupying the entire half of the right kidney. Exploration proved involvement of the kidney by a large clear cell carcinoma which had spread to lymph nodes in the pericaval chain. No attempt was made t o resect the tumour. Silver clips were applied to the mass to direct radiation therapy.
The patient had an uneventful post-operative recovery and radiation therapy to the right kidney region was started 10 days after his operation. He received a series of 17 treatments with Cobalt 60 teletherapy (3,500 rads). Therapy was discontinued because of anorexia and malaise. Three months later his N.P.N. was found to be 63 mg. per 100 ml., blood urea nitrogen was 35 and creatinine 3.7.
The patient lived for one and one-half years following his operation and radiotherapy, finally succumbing to carcinoma spread.
Case 2.-F. S., V.A. No. 2571, a 51-year-old Caucasian man, complained of blood in the urine and right flank pain. The symptoms first occurred eight months prior to admission at which time an intravenous urogram showed absence of the left kidney and a stone in the right ureter. The calculus was removed cystoscopically. Seven additional hospitalisations were required because of hamaturia and right flank pain. Two weeks prior to his admission he underwent a surgical exploration at another hospital. A large tumour in the upper pole of the right kidney was considered inoperable because the patient had only one kidney; a pyelostomy was performed.
Chest X-ray and a skeletal survey disclosed no evidence of metastases. An X-ray made after injection of the pyelostomy tube revealed a deformity of the calyces compatible with kidney tumour (Fig. 1). Serum creatinine was 1.9 mg. per 100 ml. and the alkaline phosphatase was 11.4 units.
Through a flank incision approximately 25 per cent. of the kidney was removed by resecting the upper pole turnour. It was necessary t o transect a large vein and two calyces required closure by sutures. The right adrenal gland was also removed. Output post-operatively was satisfactory but the day after operation the blood pressure drifted downward. The patient ran a febrile course and on the third post-operative day was given chloramphenicol &cause of Gram-positive cocci in the blood culture. Chest X-ray showed patchy bilateral pneumonia. Three days post-operatively the serum creatinine was 5.6 mg. per 100 ml. but at eight days it was 2.1. The patient died suddenly on the tenth post-operative day. Autopsy showed bronchopneumonia and congenital absence of the left kidney and ureter. There was some haemorrhage in the area of resection of the right kidney but otherwise it appeared to be normal. There was no evidence of residual tumour in the kidney and no metastases were identified.
1 Supported in part by the University of California at Los Angeles Cancer Research Institutional Grant. 12
R E N A L CELL CARCINOMA I N SOLITARY K I D N E Y 13
FIG. 1
calyces compatible with kidney tumour. Case 2. Pyelogram (via pyelostomy) of soli!ary right kidney showing deformity of the
Case 3.-Eight years before his U.C.L.A. hospital admission J. L., 01 3-84-45, a 55-year-old Caucasian married machinist, was found to have an upper pole tumour of the right kidney for which nephrectomy was performed (Fig. 2). The renal veins were free of tumour and there was no evidence of local extension or distant metastases.
Case 3. Intravenous urogram showing upper pole right renal mass.
The diagnosis was clear cell adenocarcinoma. The patient regained his weight and did well until five months prior to this admission when his urine became blood-tinged. A retrograde urogram showed irregular effacement of the superior portion of the left renal pelvis (Fig. 3, A). Renal arteriography disclosed many abnormal vessels throughout the mid and upper portions of the left kidney with ‘‘ laking ” of contrast medium and early visualisa- tion of the left renal vein indicating the presence of an intrarenal arteriovenous fistula (Fig. 3, B).
Serum creatinine was 1.2 mg. per 100 ml. Serum alkaline phosphatase was normal and sedimentation rate was 32 mm./hr. Chest X-ray examination disclosed no evidence of pulmonary metastases.
14 BRITISH JOURNAL O F UROLOGY
At operation (eleventh interspace approach) a hypernephroma approximately 6 cm. in diameter was found on the superior and anterior surfaces of the kidney. After ligation of a branch of the renal artery supplying the anterior portion of the upper pole it appeared possible to remove most of the tumour without excessive sacrifice of renal tissue. A small lower pole tumour nodule was excised and fulgurated. Open vessels &ere suture-ligated and the cut infundibula were repaired with fine chromic catgut. Ischiemia time was 34 minutes. Good hiemostasis was achieved on the large cut surface of the kidney.
FIG. 3 A, Case 3. Retrograde urogram showing displacement of calyces of the solitary left kidney,
eight years after the removal of the right kidney for hypernephroma. B, Case 3. Selective arteriogram showing many abnormal vessels throughout the mid and
upper portions of the left kidney.
The serum creatinine of 1.2 mg. per 100 ml. on admission rose to 3.1 on the third post-operative day despite an inadequate urinary output. By the eleventh post-operative day the creatinine was 2.7 and on the thirtieth post-operative day it was 2-1 mg. per 100 ml.
The resected tumour was identified histologically as renal adenocarcinoma. There was no evidence of involvement of local lymph nodes or renal veins. It was reasonably certain, however, that residual tumour was present in the kidney and at 3+ months after the operation the patient showed pulmonary metastases and persistent urinary drainage through a flank sinus. He was started on hormonal therapy with testosterone at this time. He lived for 6 months.
Case 4.-H.H. U.C.L.A. 034-18-04, a 59-year-old man, had fever of two months’ duration. Four years earlier, after several months of fever and shaking chills, he was found to have a mass in the upper portion of the right kidney (Fig. 4). Nephrectomy was delayed for two years. When it was finally performed the kidney was found to contain an adenocarcinoma with no evidence of local node involvement.
At the time of admission to hospital the heart and lungs were normal. Hiemoglobin was 10.5 g., sedimentation rate 30 mm. per hour, serum alkaline phosphatase 12.2 King Armstrong units and creatinine 0.9 mg. per 100 ml. Bone survey showed no evidence of metastatic disease but chest X-ray revealed a left hilar mass consistent with metastatic tumour. An intravenous urogram disclosed slight irregularity of the lateral contour of the solitary left kidney with minimal calyceal displacement. Nephrotomography showed a mass on the lateral contour of the left kidney and on selective arteriography a 6 cm. tumour with vascular tortuosity and “ laking ” typical of renal cell carcinoma was observed (Fig. 5) .
The kidney was explored through the eleventh interspace. The tumour was confined t o the lateral part of the kidney and there was no evidence of extrarenal tumour. The renal artery was temporarily occluded while the tumour was excised. A large vein required suture closure and a transected calyx was closed.
The 70 g. tumour measured 5 x4 cm. in size. It was well circumscribed and in most portions there was a 1 cm. margin of normal kidney. Microscopically it was a clear cell carcinoma. The urine output in the first 24 hours post-operatively was 1,538 ml. and in the next 24 hours, 2,074 ml. and it continued to be adequate. Blood creatinine rose from a pre-operative level of 0.9 to 2.3 mg. per 100 ml., but by the fourth post-operative day it had dropped to 1.6 mg. per cent.
R E N A L C E L L C A R C I N O M A I N S O L I T A R Y K I D N E Y
FIG. 4 Case 4. Intravenous urogram showing upper pole tumour right kidney.
FIG. 5
Tumour I S seen on the lateral surface of the kidney. Case 4. Selective left arteriogram made two years after rernova of right kidney for hypernephroma.
15
2
16 BRITISH J O U R N A L OF UROLOGY
During the next three months there was a fall in the sedimentation rate to 18 mm. per hour. An intravenous urogram showed a smooth contour of the left kidney. Because the chest X-ray showed an increase in size of the irregular left hilar mass an exploratory thoracotomy was performed. A 3 x 4 x 3 cm. lesion was found in the superior segment of the lower lung lobe adjacent to the main bronchus. Left lower lobectomy was performed and lymph nodes were removed with the specimen. Microscopically the tumour showed large pleomorphic cells with hyper- chromic nuclei and abundant vacuolated cytoplasm consistent with metastatic renal cell adenocarcinoma. The tumour did not extend to the pleura. No tumour was found in sections of seven enlarged lymph nodes.
Following a satisfactory recovery from this operation the patient continued to do well and returned to work. Chest X-ray post-operatively showed disappearance of the left hilar mass. Sedimentation rate returned to normal and there has been no fever during a follow-up period of two and a half years.
Case 5,-U.C.L.A. No. 037-36-87, a &year-old Caucasian woman, had a right nephrectomy in August 1958 for hypernephroma. No nerve involvement or perirenal extension was noted. Gross haematuria reappeared in
FIG. 6 Case 5. Selective arteriogram of solitary left kidne showing diffuse laking characteristic of renal cell carcinoma anioccurring
eight years following right nephrectomy for renal cell tumour.
December 1965 but the patient delayed seeing a physician until June 1966, when bleeding became more pronounced and she became aware of a mass in the left flank. She denied fever or weight loss.
An intravenous urogram revealed an upper pole mass in the left kidney and surgical absence of the right kidney. Arteriography disclosed a large mass occupying the superior portion of the left kidney with diffuse splotchy appearance of contrast medium characteristic of renal cell carcinoma (Fig. 6). The right adrenal also " lighted-up " with contrast medium and suggested metastatic tumour involvement.
Although resection of the tumour was considered non-feasible because of its diffuse character, exploratory laparotomy was performed for biopsy and silver clip marking to aid in directing radiotherapy. The right adrenal was egg-sized and involved by tumour while the left kidney contained a large tumour at its upper pole with smaller satellite nodules scattered in the remaining portions of kidney.
R E N A L CELL CARCINOMA IN SOLITARY K I D N E Y 17
The patient was started on hormonal therapy with testosterone 100 mg. daily and Co-60 teletherapy to the areas of tumour. Her condition was stable for three months but she then had a downhill course and died of metastatic disease six months after her operation.
Case 6.-U.C.L.A. No. 039-69-81, a 45-year-old Caucasian woman, was found to have congenital absence of the left kidney as proven by the excretory urogram, aortogram and absence of the left half of the trigone. She presented with severe pain in the right flank of one month’s duration and was found to have a large mass in the upper pole of the solitary right kidney. Arteriography disclosed a large mass occupying the upper pole of the kidney and normal vascular pattern to the lower half of the kidney (Fig. 7, A). There was no evidence of metastases
A, Case 6. Pre-operative aortogram showing large tumour arising in upper pole of solitary right kidney.
B, Case 6. Selective right arteriogram nine months after resection of the upper,pole tumour. There is no gross evidence of tumour recurrence but tumour was found in the perirenal area on
selective lumbar arteriography.
in the chest X-ray. A right heminephrectomy was performed through a thoraco-abdominal incision in March 1967. There appeared to be no evidence of perirenal spread. The ischlemia time necessary to effect an upper heminephrectomy was 24 minutes. Her post-operative convalescence was uneventful. There was no period of oliguria and when she was discharged on the eleventh post-operative day her blood creatinine was 1.0. The patient continued to do well for seven months, a t which time she felt well but began to complain of pain in the right flank. Eight months post-operatively she noted blood tinging of the urine.
The portion of the kidney remaining after resection of the tumour appeared normal on intravenous urography and selective arteriography (Fig. 7, B) but a further renal arteriogram performed with injection of epinephrine showed a small area of tumour near the hilus of the kidney. Selective injection of a lumbar artery showed tumour recurrence in the perirenal area. The patient was treated by leaving a catheter indwelling in the renal artery and injecting epinephrine to cause constriction of the renal arterial branches at the time of administration of super- voltage radiotherapy to the renal and perirenal area (renal sparing effect).
DISCUSSION
Data regarding the 27 recorded cases of renal cell carcinoma in the solitary kidney are given in Table I and summarised in Tables I1 and 111. In 13 cases the opposite kidney was congenitally absent or dysplastic. In four cases nephrectomy had been performed for tubercu- losis, pyelonephritis or hydronephrosis; in the remaining 10 cases for carcinoma. The fact
18 B R I T I S H J O U R N A L OF U R O L O G Y
Semb
Colston Svab Kerr Meyer et al.
Klotz
Smith Andre
Ballanger Ewert Fleming and
Dick Rolnick et al. Malament
Ward-McQuaid
Gray and Biorn Bloom
McDonald and Flanagan
Kaufman et al. Kaufman et al. Kaufman et a/.
Kaufman et al.
Kaufman et al.
Kaufman et al.
- . . - . - -.
Author
Beilin and Neiman
Senger et al.
Bailey and Youngblood
Borski and Kimbrough
TABLE I Renal Cell Carcinoma in the Solitary Kidney
teference Year
1942
1947
1950
1954
1954
1955 1956 1959 1960
1960
1961 1962
1962 1962 1964
1964 1965 1965
1967 1967
1967
1968 1968 1968
1968
1968
1968
~~_______
Data re Other Kidney
Nephrectomy for renal cell carcinoma 6 years ago
Nephrectomy for renal cell carcinoma 2 years ago
Nephrectomy for renal cell carcinoma 11 years ago
Nephrectomy for renal cell carcinoma 3 years ago
Nephrectomy for renal tuberculosis
Agenesis Agenesis Agenesis Nephrectomy for renal cell
carcinoma 2 years ago
Nephrectomy for renal cell carcinoma 20 years ago
Dysplasia Nephrectomy for pyelone-
phritis 11 years earlier Agenesis Agenesis Agenesis
Atrophic non-functioning Agenesis Nephrectomy for renal cell
carcinoma 4 years ago
Agenesis Nephrectomy for renal
tuberculosis Nephrectomy for
pyohydronephrosis Agenesis Agenesis Nephrectomy for renal cell
carcinoma 4 years ago Nephrectomy for renal cell
carcinoma 8 years ago Nephrectomy for renal cell
carcinoma 8 years ago
Agenesis
Treatment
None
Biopsy and
None
Biopsy and
Partial nephrectomy
Partial nephrectomy Partial nephrectomy Partial nephrectomy Exploration and
chemotherapy perfusion
Partial nephrectomy
Partial nephrectomy Partial nephrectomy
Partial nephrectomy Partial nephrectomy Partial nephrectomy
Partial nephrectomy Partial nephrectomy Biopsy, X-ray
radiotherapy
radiotherapy
radiotherapy
Partial nephrectomy Provera and
Partial nephrectomy
Biopsy, X-ray Partial nephrectomy Partial nephrectomy,
lobectomy Partial nephrectomy,
testosterone Biopsy, X-ray,
radiotherapy, testosterone
testosterone
Partial nephrectomy
Survival after Diagnosis of
Tumour Solitary Kidney
Dead 23years
Dead 3 + years
Dead 3 years
Dead 23years
? ?
Dead 4fmonths Alive 1 year Alive 4 months Dead 9 months
Alive 1 year
Alive 16 months Alive 10 years
Alive 15 months Alive ? months Alive 2 years
Alive 5 months Dead 5 months Dead 14 years 01
renal carcinom
Alive 5 years Dead 3 months
Alive 5 years
Dead If years Dead 10 days Alive 23 years
Dead 6months
Dead 6 months
Alive 9 months
R E N A L CELL C A R C I N O M A I N SOLITARY K I D N E Y 19
that almost one-half of the patients had a history of previous nephrectomy for carcinoma introduces the question of whether such tumours arising in sole remaining kidneys represent new growths or metastatic lesions. This is still a moot issue but the evidence suggests that such tumours are metastatic rather than primary. We have found 12 references to the occurrence of bilateral hypernephromas in the literature. Bilaterality may not be as common in this type of tumour as in Wilms’ tumour (3 to 5 per cent.), but it occurs with sufficient frequency to be considered when bilateral renal masses are found or when tumour occurs in a kidney after its mate has been removed for carcinoma.
TABLE I1 Renal Cell Carcinoma in the Solitary Kidney
No. of cases reported = 27 (1942-68) Other kidney
Congenital absence or dysplasia = 13 Nephrectomy for tuberculosis = 2 Nephrectomy for pyelonephritis = 2 Nephrectomy for carcinoma = 10
Average interval between nephrectomy for carcinoma and tumour in remain- ing kidney = 6f years (6 months to 20 years).
TABLE I11 Renal Cell Carcinoma in the Solitary Kidney
I Treatment 1 Number of Cases 1 Survival Reported
None 2 Biopsy and radiation
Chemoperfusion Partial nephrectomy Hormonal therapy
1 18
1 I
2 t and 3 years 2 months, 14, 2f, 3 +
and 14 years 9 months 3 months to 10 years 3 months
Prolonged survivals after the diagnosis of inoperable carcinoma have been documented in significant numbers. Mims et al. (1966) recently reported the results at our institution following nephrectomy for carcinoma in the presence of “ incurable ’’ local extension or distant metastases. Fourteen of 96 patients had evidence of lymph node extension, renal vein invasion, or extension through the renal capsule. Three survived at least 10 years. Each of these patients had radical surgery to remove the primary lesion and two of the three had post-operative irradiation.
Spontaneous regressions of renal tumours have also been reported in significant numbers. Goodwin et al. (1967) recently reviewed this subject and compiled 21 documented cases. We reported four additional cases of spontaneous regression, and in personal communications reported that approximately 25 additional instances had been witnessed by a small sampling of urologists. On the basis of this survey, the authors feel justified in recommending surgical removal of seemingly incurable hypernephroma in most cases, even when local invasion or distal metastases are present.
Although spontaneous regression is extremely rare, there is general agreement that solitary. resectable metastases of hypernephroma should be treated by excision. Riches, Griffiths and
20 B R I T I S H J O U R N A L OF UROLOGY
Thackray (1951) reCorted survivals after removal of apparent solitary metastases in seven cases followed from four months to one year. Solitary metastases have been excised from the cere- bellum, lung, bone, thyroid, testis and vagina. There have been instances of long survivals with hypernephroma without treatment. Recently a report of renal carcinoma recurring 31 years after nephrectomy has been made by Kradjian and Bennington (1965).
The points enumerated support the thesis that an aggressive approach to tumours occurring in solitary kidneys is justified. Eighteen cases which have been treated by partial nephrectomy have reported survivals of three months to 10 years. Vermooten (1950) was the first to suggest that partial nephrectomy be performed for malignant growths of the kidney, even when the other kidney is considered normal. He felt that a peripheral clear cell adenocarcinoma of the kidney justified local excision. Partial nephrectomy is feasible not only for tumours at either pole, but in middle segments of the kidney as well. Resection of tumour from a superficial portion of the kidney presents no momentous surgical problem (Case 4). When larger areas of tumour involvement occur, partial nephrectomy may present serious difficulties and hazards, although with the compensatory hypertrophy usually present, resection of as much as 50 per cent. of the kidney can be done without major loss of renal function. The principal deterrent in such cases, however, is that tumours of such large size frequently have local extensions (Cases 1, 3 and 5). Because chemotherapy has little to offer and because radiation treatment of the solitary kidney is deleterious to renal function, excisional therapy is to be recommended wherever it can be safely accomplished. The removal of large portions of the solitary kidney requires preliminary control of the renal artery, cooling of the kidney with iced saline whenever the period of ischaemia is estimated to be over 30 minutes, and careful closure of open vessels, calyces and infundibula. Preoperative intravenous mannitol infusions have been shown to be of value. In the future dextran and chlorpromazine may be useful for their protective action during total renal ischaemia. Partial nephrectomy in Case 3 was ill-advised considering the extent of the tumour within the kidney and the multiplicity of lesions in the solitary kidney.
Bloom (1967) has reported subjective improvement in 17 of 39 patients with near terminal renal carcinoma who were treated with testosterone or Provera. Objective regressions occurred in eight of the 38 patienu. The best responses were observed in men who were treated with Provera, 100 mg. by mouth, three times daily, or testosterone, 100 mg. intramuscularly five days a week. This form of therapy is based on the observation of tumour induction in the hamster by estrogens and inhibition of tumorigenesis by the simultaneous administration of testosterone or progesterone. The value of this form of palliation needs confirmation.
A method of destroying renal cell carcinoma with radiation while avoiding radiation nephritis has recently been conceived by Steckel et al. (1967). In experimental studies they infused epinephrine into one renal artery during the delivery of 1,500 rads of radiation to both kidneys. The kidney receiving epinephrine during the radiation therapy was spared both microscopically and functionally while the " unprotected " kidney showed fibrosis, shrinking and loss of function. The authors postulate that epinephrine exerts its protective effect during radiation by producing vasoconstriction, a decrease in renal blood flow and temporary renal anoxia. (Tissue oxygenation is the single most important factor in tissue radiosensitivity.) Unlike normal vessels, tumour vessels do not constrict in response to epinephrine infusion, allowing an opportunity to achieve a greater destructive effect of radiation on the tumour while sparing normal renal tissue which can be made temporarily anoxic by the epinephrine-induced ischaemia. This interesting form of treatment is being evaluated in our Case 6, but it is too soon to know the results.
SUMMARY Twenty-one cases of renal cell carcinoma occurring in the solitary kidney have been
collected and six have been added. One patient is doing well and is apparently tumour-free
RENAL CELL CARCINOMA I N SOLITARY K I D N E Y 21
after removal of a tumour in a solitary kidney followed by lobectomy for a solitary pulmonary nodule. Some long survivals following partial nephrectomy for tumours in the solitary kidney and the propensity of this tumour to regress or to become latent for long intervals justify aggressive approaches. Arteriography has aided in establishing the diagnosis, in defining the areas of tumour involvement and in demonstrating the arterial distribution in the kidney. Knowledge of the vascular architecture of the kidney, improved surgical skills and judicious use of chemotherapy and radiotherapy will all help to salvage some patients with this infrequent but challenging problem.
Addendum.-In personal communications we have learned that Dr H. Grabstald of Memorial Hospital for Cancer and Allied Diseases will soon report five additional cases of renal cell carcinoma in the solitary kidney and that Dr A. Puigvert of Barcelona has one case of partial nephrectomy for hypernephroma in a solitary kidney with a post-operative survival of six and a half years.
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