Vol. 113, June
THE JOURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
Printed in U.S.A.
URETERAL CARCINOMA IN SITU DONALD G. LINKER*
AND
WILLET F. WHITMORE
From the Urologic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, and the Division of Urology, University of California School of Medicine, San Francisco, California
ABSTRACT
The incidence of ureteral carcinoma in situ at the time of cystectomy for bladder carcinoma is approximately 8. 7 per cent. Followup records of 27 such patients as well as records of 6 patients with other ureteral abnormalities were reviewed. Clinically, no postoperative ureteral or upper urinary tract difficulty was noted in 29 of the 30 patients whose records were complete. The ureteral status of the 3 patients lost to followup remains uncertain. One patient had infiltrating ureteral carcinoma and he is well 8 years after cystectomy. Since ureteral carcinoma in situ at the time of cystectomy for bladder cancer has had little influence on the course of these patients, conservative treatment is probably indicated when the lesion is encountered. The occurrence of carcinoma in situ of the ureter in association with bladder carcinoma is well documented. i-s Sharma and associates reported on 17 cases of carcinoma in situ among 205 patients who had undergone cystectomy for bladder cancer at our center. 4 The followup of these patients and further data on the incidence of ureteral carcinoma in situ at the time of cystectomy for vesical cancer form the basis of this report. MATERIAL AND METHODS
Followup records of 17 patients with ureteral carcinoma in situ at the time of cystectomy whose cases were previously reported from this institution were reviewed. 4 In addition, the records of 107 patients who underwent cystectomy for vesical cancer from January 1969 to June 1971 were examined. Ureteral segments (1 to 3 cm. in size) from 102 of the 107 patients were excised for histologic study immediately before ureteroileal anastomosis. No serial sections were prepared. Our analysis is based on the recorded pathologic findings. OBSERVATIONS
Original series: 205 patients (fig. 1). Of 17 patients with ureteral carcinoma in situ at time of cystectomy, 13 had no difficulties attributable to the ureteral lesions, 3 were lost to followup and 1 required further surgery for progressive upper urinary tract dilatation. Of the 13 patients who experienced no additional complication from the ureteral carcinoma in situ, 6
died of metastatic bladder carcinoma an average of 35 months postoperatively. The ureteral status was anatomically defined in 2 of these 6 patients. One patient underwent nephroureterectomy 13 months after cystectomy for extrinsic ureteral obstruction secondary to metastatic bladder carcinoma, the ureteral mucosa and the renal pelvis being histologically unremarkable. Autopsy in the other case, performed 23 months after cystectomy, revealed normal ureteroileal anastomoses with metastatic bladder cancer surrounding 1 of the distal ureters. Another 4 of these 13 patients died of causes unrelated to neoplasm-2 of cardiorespiratory disease within 1 month of the operation, 1 of liver failure 8 months postoperatively and 1 of intestinal obstruction 6 years postoperatively. Autopsy of 1 of the 2 patients who died of cardiorespiratory disease demonstrated no carcinoma at the ureteroileal anastomoses. Three of the 13 patients are well 7, 7 ½ and 8 ½ years after cystectomy. Of the 3 patients lost to followup, 2 died of unrecorded causes 17 and 28 months after cystectomy, respectively. The third patient was without evidence of neoplasm when last seen 54 months postoperatively. One patient, whose case was described in detail in the original study, represents the only instance of documented progression of the ureteral carcinoma in situ. This patient had bilateral ureteral carcinoma in situ at the time of cystectomy. The ilea! loop was reconstructed 31 months later because of progressive left upper tract dilatation. In situ and infiltrating carcinomas were found at the left ureteroileal anastomosis and in situ carcinoma was found at the right anastomosis. A left nephroureterectomy for persistent ureteroileal obstruc-
Accepted for publication September 20, 1974. * Requests for reprints: Division of Urology, University of California School of Medicine, San Francisco, California 94143. 777
778
LINKER AND WHITMORE ALIVE, '5
LOST TO FOLLOWUP,3
DEAD UNRELATED CAUSES,4
PROGRESSIVE UR.ETERALCA IN SITU , 1 (&%)
DEAD., METASTATIC BLADDER CA, 6
FIG. 1. Followup of 17 patients (original series) with ureteral carcinoma in situ at time of cystectomy. Note that only 1 patient had progressive ureteral carcinoma.
tion and recurrent upper tract infection was performed 6 years after cystectomy. The pathologic findings were ureteritis and mucosal atypia at the ureteroileal anastomosis. The patient is well 8 years after cystectomy. Recent series: 107 patients (fig. 2). Of 107 patients who underwent cystectomy between January 1969 and July 1971, 9 (8.8 per cent) had ureteral carcinoma in situ, 4 with bilateral involvement. In addition, 5 patients had mucosal atypia, 1 with hyperplasia and 1 with infiltrating ureteral carcinoma. This represents an over-all incidence of 15.7 per cent of patients with ureteral abnormalities. None of the 9 patients with ureteral carcinoma in situ experienced difficulty as a result of the ureteral abnormality. Seven died within 21 months of the operation and 2 are well 52 and 57 months postoperatively. Of the 7 patients who died, 5 had metastatic bladder carcinoma at the time of death (autopsy material from 1 demonstrating only ureteritis at the ureteroileal anastomosis), 1 died of diabetic complications and 1 died of a pulmonary embolus. Autopsy in the latter patient revealed no neoplasm. The patient with infiltrating carcinoma of the ureter died 1 month postoperatively of a myocardial infarction with no evidence of carcinoma at autopsy. Of the 6 patients with ureteral atypia or hyperplasia, 3 died of metastatic bladder carcinoma within 15 months of cystectomy. No upper urinary tract abnormality was detected by pyelography or cytology. One patient died 42 months postoperatively of pneumonia and 2 are well 42 and 44 months after the operation (fig. 3). In none of the 16 patients with ureteral abnormalities has a clinical renal pelvic or ureteral carcinoma developed. In reviewing the records of the 107 patients treated by cystectomy, we found that 1 patient had undergone nephroureterectomy for atypical papillomas of the renal pelvis and upper ureter 17 months before cystectomy and
DEAD UNRELATED CAUSES,3* *INFILTRATING CA, 1
DEAD, METASTATIC BLADDER CA, 5
FIG. 2. Followup of 10 patients (recent series) with ureteral carcinoma at cystectomy. None of 9 patients with ureteral carcinoma in situ experienced further difficulty from it and 1 with ureteral infiltrating carcinoma died of unrelated cause.
DEAD UNRELATED CAUSES, 1
DEAD, METASTATIC BLADDER CA, 3
FIG. 3. Followup of 6 patients (recent series) with ureteral atypia or hyperplasia.
URETERAL CARCINOMA IN SITU
another 2 years after cystectomy for in situ and infiltrating carcinoma of the renal pelvis. In each case the ureters were normal at the time of cystectomy. Thus, in the combined groups incorporating 33 patients with ureteral abnormalities, 27 of whom had in situ or infiltrating carcinoma, only 1 patient suffered progressive carcinoma of the ureter or renal pelvis. No further difficulty relative to the ureteral abnormality was seen in 29 patients and the status of 3 patients in the latter regard remains uncertain (fig. 4). DISCUSSION
The potential for in situ bladder carcinoma to progress to invasive carcinoma is documented, 6 although the features of this process relative to frequency and time remain to be better defined. The occurrence of ureteral carcinoma in situ in patients with bladder cancer treated by cystectomy is also well documented but its clinical significance is uncertain. Culp and associates found epithelial aberrations in 17 per cent of 231 ureters at the time of partial or total cystectomy, with an almost equal distribution between in situ and infiltrating neoplasm.2 Wallace discovered 21 examples of either in situ or frank tumor in the distal portion of the ureters in 200 bladder specimens removed for bladder cancer. 5 A similar lesion was identified in the juxtavesical ureters in 18 per cent of 45 cases reviewed by Cooper and associates. 1 A third of the ureteral stumps of 30 cystectomy specimens from bladder cancer patients reported by Schade and associates contained carcinoma in situ, papillary tumors or invasive carcinoma. 3 In the original series of 205 cystectomy patients from our center, the incidence of ureteral carcinoma in situ was 8.5 per cent. 4 This incidence has been confirmed by the present study figure of 8.8 per cent. The different incidences of ureter al carcinoma in situ reported may be a result of: 1) differences in
pathologic interpretation of identical lesions, 2) differences in the extent of pathologic study of the ureter and 3) differences in the site at which the ureter was sampled. The incidence of the lesion is greatest in the juxtavesical ureter, 2 • 3 at least in the bladder cancer material which has been the basis for the limited studies to date, but the possibility of multicentric lesions of the ureter and the possible relationship of these lesions to the associated bladder tumor have yet to be defined. Followup data on patients with in situ ureteral carcinoma are sparse. Culp and associates mentioned 2 patients who had carcinoma at a higher level of the urinary tract postoperatively but stated that autopsy studies in several other instances showed no evidence of tumor at the ureteroileal anastomoses. 2 Although Schade and associates discussed obstruction of the ureter from infiltrating tumor within 3 years of operation in 2 cases recognized as having ureteral carcinoma in situ, neither was included in their specific series. However, followup of the 30 cases at intervals of as much as 2 years revealed no apparent recurrence in the ureters." Only 1 of the original 17 cases with ureteral carcinoma in situ later had invasive cancer of the ureter, 4 while followup of the 16 cases in the present series revealed no difficulty related to the ureteral abnormalities. There are several possible explanations for the discrepancy between the relatively high incidence of ureteral carcinoma in situ and the relatively low clinical incidence of related ureteral problems: 1) The carcinoma in situ may have been completely excised by the segmental ureteral excision which revealed it. Of the 30 patients with complete followup records in the combined experiences of Sharma and associates, and the present series 29 had no further recognized ureteral or upper urinary tract difficulty. In 6 of these 29 patients re-exploration or autopsy showed no evidence of neoplasm at the ureteroileal anastomoses. The ureteral status
LOST TO FOLLOWUP, 3
::::':-"""""':::.a::::.a::::.a:::.a:~ PROGRESSIVE: URE:TE:RAL CA IN SITU, 1 (3°/.)
DEAD, METASTATIC BLADDER CA, 14
FIG. 4. Followup of 33 patients (combined series) with ureteral abnormalities. Over-all incidence of progressive . ureteral carcinoma in situ is only 3 per cent.
780
i
'
LINKER AND WHITMORE
of the 3 patients lost to followup is, of course, unknown. 2) Death from other causes may have prevented the development of infiltrating ureteral carcinoma. Fourteen of the 33 patients were known to have had metastatic bladder carcinoma at the time of death. Again, in an additional 3 patients, status relative to bladder carcinoma was unsettled. Eight patients died of causes other than a urothelial neoplasm. The postoperative survivals of these 25 patients were less than 1 year in 9, 1 to 2 years in 6, 2 to 3 years in 4, 3 to 4 years in 2, 4 to 5 years in 3 (including the 1 patient who was lost to followup 54 months postoperatively) and 5 to 6 years in 1. Although the interval between the appearance of any in situ carcinoma and the development of infiltrating carcinoma probably varies with different primary sites, with different individuals having the same primary site and possibly even with the same primary site and individual at different times, precise quantitation of these variables is lacking. Evidence for the cervix 7 and for the bladder• indicates that the period of latency before in situ carcinoma becomes infiltrating may be a matter of years. 3) Infiltrating ureteral carcinoma developed but went unrecognized. Of the 28 patients who survived more than 6 months postoperatively, 2 did not have followup excretory urograms (IVPs) ( 1 died 17 months postoperatively of unknown causes and the other died 4 years postoperatively of diffuse metastases). However, absence of progressive dilatation of the upper urinary tracts detectable on the postoperative IVP may not be a reliable technique to rule out infiltrating ureteral carcinoma. Criteria for a positive cytologic diagnosis from the ileal conduit urine have been described. 8 Postoperative urinary ileal conduit cytologic studies were recorded as negative in 12 of the patients but were not performed consistently or serially as a followup examination. 4) The possibilities that ureteral carcinoma in situ may spontaneously disappear or at least remain in the in situ· stage indefinitely have not been eliminated. One of the 107 patients in the present review had a renal pelvic tumor 2 years after cystectomy and 1 had had a renal pelvic tumor 1 year before cystectomy. Both of these patients had histopathologically normal ureters at cystectomy. Wallace reported a 4 per cent incidence of upper urinary tract tumors following cystectomy for bladder carcinoma but he did not study the relationship to ureteral carcinoma in situ. 9 Sharma and associates
described a patient with ureteral carcinoma in situ in whom a renal pelvic tumor developed subsequently but this case was not 1 of the 17 cases of ureteral carcinoma in situ in their series.• Thus, although it is tempting to speculate that the manifestation of urothelial multicentricity illustrated by ureteral carcinoma in situ may be a harbinger of further upper tract tumors, present evidence suggests that this likelihood is small. Furthermore, whether the apparent over-all high mortality rate evident in those patients with ureteral carcinoma in situ at the time of cystectomy is significantly related to this manifestation of urothelial multicentricity cannot be assessed from the current analysis. The reported results suggest that ureteral carcinoma in situ is a not uncommon finding in patients undergoing cystectomy for bladder carcinoma. Although the identification of this lesion has had little evident impact on the future course of most patients in v.hom it has occurred, it would seem prudent to do frozen sections of the ureteral margins before ureteroenteric anastomosis to establish the histologic normalcy of the implanted ureter. Periodic IVP and post-cystectomy followup procedures for the bladder carcinoma patient are logical and especially pertinent if ureteral carcinoma in situ is found. REFERENCES
1. Cooper, P. H., Waisman, J., Johnston, W. H. and Skinner, D. G.: Severe atypia of transitional epithelium and carcinoma of the urinary bladder. Cancer, 31: 1055, 1973. 2. Culp, 0. S., Utz, D. C. and Harrison, E. G., Jr.: Experiences with ureteral carcinoma in situ detected during operations for vesical neoplasm. J. Urol., 97: 679, 1967. 3. Schade, R. 0. K., Serck-Hanssen, A. and Swinney, J.: Morphological changes in the ureter in cases of bladder carcinoma. Cancer, 27: 1267, 1971. 4. Sharma, T. C., Melamed, M. R. and Whitmore, W. F., Jr.: Carcinoma in-situ of the ureter in patients with bladder carcinoma treated by cystectomy. Cancer, 26: 583, 1970. 5. Wallace, D.: Cancer of the bladder. Amer. J. Roentgen., 102: 581, 1968. 6. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 7. Boyes, D. A., Fidler, H. K. and Lock, D. R.: Significance of in situ carcinoma of the uterine cervix. Brit. Med. J., 1: 203, 1962. 8. Wolinska, W. H. and Melamed, M. R.: Urinary conduit cytology. Cancer, 32: 1000, 1973. 9. Wallace, D. M.: Tumours of the ureter. Proc. Roy. Soc. Med., 62: 94, 1969.
THE JOURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
Printed in U.S.A.
URETERAL CARCINOMA IN SITU DONALD G. LINKER*
AND
WILLET F. WHITMORE
From the Urologic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, and the Division of Urology, University of California School of Medicine, San Francisco, California
ABSTRACT
The incidence of ureteral carcinoma in situ at the time of cystectomy for bladder carcinoma is approximately 8. 7 per cent. Followup records of 27 such patients as well as records of 6 patients with other ureteral abnormalities were reviewed. Clinically, no postoperative ureteral or upper urinary tract difficulty was noted in 29 of the 30 patients whose records were complete. The ureteral status of the 3 patients lost to followup remains uncertain. One patient had infiltrating ureteral carcinoma and he is well 8 years after cystectomy. Since ureteral carcinoma in situ at the time of cystectomy for bladder cancer has had little influence on the course of these patients, conservative treatment is probably indicated when the lesion is encountered. The occurrence of carcinoma in situ of the ureter in association with bladder carcinoma is well documented. i-s Sharma and associates reported on 17 cases of carcinoma in situ among 205 patients who had undergone cystectomy for bladder cancer at our center. 4 The followup of these patients and further data on the incidence of ureteral carcinoma in situ at the time of cystectomy for vesical cancer form the basis of this report. MATERIAL AND METHODS
Followup records of 17 patients with ureteral carcinoma in situ at the time of cystectomy whose cases were previously reported from this institution were reviewed. 4 In addition, the records of 107 patients who underwent cystectomy for vesical cancer from January 1969 to June 1971 were examined. Ureteral segments (1 to 3 cm. in size) from 102 of the 107 patients were excised for histologic study immediately before ureteroileal anastomosis. No serial sections were prepared. Our analysis is based on the recorded pathologic findings. OBSERVATIONS
Original series: 205 patients (fig. 1). Of 17 patients with ureteral carcinoma in situ at time of cystectomy, 13 had no difficulties attributable to the ureteral lesions, 3 were lost to followup and 1 required further surgery for progressive upper urinary tract dilatation. Of the 13 patients who experienced no additional complication from the ureteral carcinoma in situ, 6
died of metastatic bladder carcinoma an average of 35 months postoperatively. The ureteral status was anatomically defined in 2 of these 6 patients. One patient underwent nephroureterectomy 13 months after cystectomy for extrinsic ureteral obstruction secondary to metastatic bladder carcinoma, the ureteral mucosa and the renal pelvis being histologically unremarkable. Autopsy in the other case, performed 23 months after cystectomy, revealed normal ureteroileal anastomoses with metastatic bladder cancer surrounding 1 of the distal ureters. Another 4 of these 13 patients died of causes unrelated to neoplasm-2 of cardiorespiratory disease within 1 month of the operation, 1 of liver failure 8 months postoperatively and 1 of intestinal obstruction 6 years postoperatively. Autopsy of 1 of the 2 patients who died of cardiorespiratory disease demonstrated no carcinoma at the ureteroileal anastomoses. Three of the 13 patients are well 7, 7 ½ and 8 ½ years after cystectomy. Of the 3 patients lost to followup, 2 died of unrecorded causes 17 and 28 months after cystectomy, respectively. The third patient was without evidence of neoplasm when last seen 54 months postoperatively. One patient, whose case was described in detail in the original study, represents the only instance of documented progression of the ureteral carcinoma in situ. This patient had bilateral ureteral carcinoma in situ at the time of cystectomy. The ilea! loop was reconstructed 31 months later because of progressive left upper tract dilatation. In situ and infiltrating carcinomas were found at the left ureteroileal anastomosis and in situ carcinoma was found at the right anastomosis. A left nephroureterectomy for persistent ureteroileal obstruc-
Accepted for publication September 20, 1974. * Requests for reprints: Division of Urology, University of California School of Medicine, San Francisco, California 94143. 777
778
LINKER AND WHITMORE ALIVE, '5
LOST TO FOLLOWUP,3
DEAD UNRELATED CAUSES,4
PROGRESSIVE UR.ETERALCA IN SITU , 1 (&%)
DEAD., METASTATIC BLADDER CA, 6
FIG. 1. Followup of 17 patients (original series) with ureteral carcinoma in situ at time of cystectomy. Note that only 1 patient had progressive ureteral carcinoma.
tion and recurrent upper tract infection was performed 6 years after cystectomy. The pathologic findings were ureteritis and mucosal atypia at the ureteroileal anastomosis. The patient is well 8 years after cystectomy. Recent series: 107 patients (fig. 2). Of 107 patients who underwent cystectomy between January 1969 and July 1971, 9 (8.8 per cent) had ureteral carcinoma in situ, 4 with bilateral involvement. In addition, 5 patients had mucosal atypia, 1 with hyperplasia and 1 with infiltrating ureteral carcinoma. This represents an over-all incidence of 15.7 per cent of patients with ureteral abnormalities. None of the 9 patients with ureteral carcinoma in situ experienced difficulty as a result of the ureteral abnormality. Seven died within 21 months of the operation and 2 are well 52 and 57 months postoperatively. Of the 7 patients who died, 5 had metastatic bladder carcinoma at the time of death (autopsy material from 1 demonstrating only ureteritis at the ureteroileal anastomosis), 1 died of diabetic complications and 1 died of a pulmonary embolus. Autopsy in the latter patient revealed no neoplasm. The patient with infiltrating carcinoma of the ureter died 1 month postoperatively of a myocardial infarction with no evidence of carcinoma at autopsy. Of the 6 patients with ureteral atypia or hyperplasia, 3 died of metastatic bladder carcinoma within 15 months of cystectomy. No upper urinary tract abnormality was detected by pyelography or cytology. One patient died 42 months postoperatively of pneumonia and 2 are well 42 and 44 months after the operation (fig. 3). In none of the 16 patients with ureteral abnormalities has a clinical renal pelvic or ureteral carcinoma developed. In reviewing the records of the 107 patients treated by cystectomy, we found that 1 patient had undergone nephroureterectomy for atypical papillomas of the renal pelvis and upper ureter 17 months before cystectomy and
DEAD UNRELATED CAUSES,3* *INFILTRATING CA, 1
DEAD, METASTATIC BLADDER CA, 5
FIG. 2. Followup of 10 patients (recent series) with ureteral carcinoma at cystectomy. None of 9 patients with ureteral carcinoma in situ experienced further difficulty from it and 1 with ureteral infiltrating carcinoma died of unrelated cause.
DEAD UNRELATED CAUSES, 1
DEAD, METASTATIC BLADDER CA, 3
FIG. 3. Followup of 6 patients (recent series) with ureteral atypia or hyperplasia.
URETERAL CARCINOMA IN SITU
another 2 years after cystectomy for in situ and infiltrating carcinoma of the renal pelvis. In each case the ureters were normal at the time of cystectomy. Thus, in the combined groups incorporating 33 patients with ureteral abnormalities, 27 of whom had in situ or infiltrating carcinoma, only 1 patient suffered progressive carcinoma of the ureter or renal pelvis. No further difficulty relative to the ureteral abnormality was seen in 29 patients and the status of 3 patients in the latter regard remains uncertain (fig. 4). DISCUSSION
The potential for in situ bladder carcinoma to progress to invasive carcinoma is documented, 6 although the features of this process relative to frequency and time remain to be better defined. The occurrence of ureteral carcinoma in situ in patients with bladder cancer treated by cystectomy is also well documented but its clinical significance is uncertain. Culp and associates found epithelial aberrations in 17 per cent of 231 ureters at the time of partial or total cystectomy, with an almost equal distribution between in situ and infiltrating neoplasm.2 Wallace discovered 21 examples of either in situ or frank tumor in the distal portion of the ureters in 200 bladder specimens removed for bladder cancer. 5 A similar lesion was identified in the juxtavesical ureters in 18 per cent of 45 cases reviewed by Cooper and associates. 1 A third of the ureteral stumps of 30 cystectomy specimens from bladder cancer patients reported by Schade and associates contained carcinoma in situ, papillary tumors or invasive carcinoma. 3 In the original series of 205 cystectomy patients from our center, the incidence of ureteral carcinoma in situ was 8.5 per cent. 4 This incidence has been confirmed by the present study figure of 8.8 per cent. The different incidences of ureter al carcinoma in situ reported may be a result of: 1) differences in
pathologic interpretation of identical lesions, 2) differences in the extent of pathologic study of the ureter and 3) differences in the site at which the ureter was sampled. The incidence of the lesion is greatest in the juxtavesical ureter, 2 • 3 at least in the bladder cancer material which has been the basis for the limited studies to date, but the possibility of multicentric lesions of the ureter and the possible relationship of these lesions to the associated bladder tumor have yet to be defined. Followup data on patients with in situ ureteral carcinoma are sparse. Culp and associates mentioned 2 patients who had carcinoma at a higher level of the urinary tract postoperatively but stated that autopsy studies in several other instances showed no evidence of tumor at the ureteroileal anastomoses. 2 Although Schade and associates discussed obstruction of the ureter from infiltrating tumor within 3 years of operation in 2 cases recognized as having ureteral carcinoma in situ, neither was included in their specific series. However, followup of the 30 cases at intervals of as much as 2 years revealed no apparent recurrence in the ureters." Only 1 of the original 17 cases with ureteral carcinoma in situ later had invasive cancer of the ureter, 4 while followup of the 16 cases in the present series revealed no difficulty related to the ureteral abnormalities. There are several possible explanations for the discrepancy between the relatively high incidence of ureteral carcinoma in situ and the relatively low clinical incidence of related ureteral problems: 1) The carcinoma in situ may have been completely excised by the segmental ureteral excision which revealed it. Of the 30 patients with complete followup records in the combined experiences of Sharma and associates, and the present series 29 had no further recognized ureteral or upper urinary tract difficulty. In 6 of these 29 patients re-exploration or autopsy showed no evidence of neoplasm at the ureteroileal anastomoses. The ureteral status
LOST TO FOLLOWUP, 3
::::':-"""""':::.a::::.a::::.a:::.a:~ PROGRESSIVE: URE:TE:RAL CA IN SITU, 1 (3°/.)
DEAD, METASTATIC BLADDER CA, 14
FIG. 4. Followup of 33 patients (combined series) with ureteral abnormalities. Over-all incidence of progressive . ureteral carcinoma in situ is only 3 per cent.
780
i
'
LINKER AND WHITMORE
of the 3 patients lost to followup is, of course, unknown. 2) Death from other causes may have prevented the development of infiltrating ureteral carcinoma. Fourteen of the 33 patients were known to have had metastatic bladder carcinoma at the time of death. Again, in an additional 3 patients, status relative to bladder carcinoma was unsettled. Eight patients died of causes other than a urothelial neoplasm. The postoperative survivals of these 25 patients were less than 1 year in 9, 1 to 2 years in 6, 2 to 3 years in 4, 3 to 4 years in 2, 4 to 5 years in 3 (including the 1 patient who was lost to followup 54 months postoperatively) and 5 to 6 years in 1. Although the interval between the appearance of any in situ carcinoma and the development of infiltrating carcinoma probably varies with different primary sites, with different individuals having the same primary site and possibly even with the same primary site and individual at different times, precise quantitation of these variables is lacking. Evidence for the cervix 7 and for the bladder• indicates that the period of latency before in situ carcinoma becomes infiltrating may be a matter of years. 3) Infiltrating ureteral carcinoma developed but went unrecognized. Of the 28 patients who survived more than 6 months postoperatively, 2 did not have followup excretory urograms (IVPs) ( 1 died 17 months postoperatively of unknown causes and the other died 4 years postoperatively of diffuse metastases). However, absence of progressive dilatation of the upper urinary tracts detectable on the postoperative IVP may not be a reliable technique to rule out infiltrating ureteral carcinoma. Criteria for a positive cytologic diagnosis from the ileal conduit urine have been described. 8 Postoperative urinary ileal conduit cytologic studies were recorded as negative in 12 of the patients but were not performed consistently or serially as a followup examination. 4) The possibilities that ureteral carcinoma in situ may spontaneously disappear or at least remain in the in situ· stage indefinitely have not been eliminated. One of the 107 patients in the present review had a renal pelvic tumor 2 years after cystectomy and 1 had had a renal pelvic tumor 1 year before cystectomy. Both of these patients had histopathologically normal ureters at cystectomy. Wallace reported a 4 per cent incidence of upper urinary tract tumors following cystectomy for bladder carcinoma but he did not study the relationship to ureteral carcinoma in situ. 9 Sharma and associates
described a patient with ureteral carcinoma in situ in whom a renal pelvic tumor developed subsequently but this case was not 1 of the 17 cases of ureteral carcinoma in situ in their series.• Thus, although it is tempting to speculate that the manifestation of urothelial multicentricity illustrated by ureteral carcinoma in situ may be a harbinger of further upper tract tumors, present evidence suggests that this likelihood is small. Furthermore, whether the apparent over-all high mortality rate evident in those patients with ureteral carcinoma in situ at the time of cystectomy is significantly related to this manifestation of urothelial multicentricity cannot be assessed from the current analysis. The reported results suggest that ureteral carcinoma in situ is a not uncommon finding in patients undergoing cystectomy for bladder carcinoma. Although the identification of this lesion has had little evident impact on the future course of most patients in v.hom it has occurred, it would seem prudent to do frozen sections of the ureteral margins before ureteroenteric anastomosis to establish the histologic normalcy of the implanted ureter. Periodic IVP and post-cystectomy followup procedures for the bladder carcinoma patient are logical and especially pertinent if ureteral carcinoma in situ is found. REFERENCES
1. Cooper, P. H., Waisman, J., Johnston, W. H. and Skinner, D. G.: Severe atypia of transitional epithelium and carcinoma of the urinary bladder. Cancer, 31: 1055, 1973. 2. Culp, 0. S., Utz, D. C. and Harrison, E. G., Jr.: Experiences with ureteral carcinoma in situ detected during operations for vesical neoplasm. J. Urol., 97: 679, 1967. 3. Schade, R. 0. K., Serck-Hanssen, A. and Swinney, J.: Morphological changes in the ureter in cases of bladder carcinoma. Cancer, 27: 1267, 1971. 4. Sharma, T. C., Melamed, M. R. and Whitmore, W. F., Jr.: Carcinoma in-situ of the ureter in patients with bladder carcinoma treated by cystectomy. Cancer, 26: 583, 1970. 5. Wallace, D.: Cancer of the bladder. Amer. J. Roentgen., 102: 581, 1968. 6. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 7. Boyes, D. A., Fidler, H. K. and Lock, D. R.: Significance of in situ carcinoma of the uterine cervix. Brit. Med. J., 1: 203, 1962. 8. Wolinska, W. H. and Melamed, M. R.: Urinary conduit cytology. Cancer, 32: 1000, 1973. 9. Wallace, D. M.: Tumours of the ureter. Proc. Roy. Soc. Med., 62: 94, 1969.
