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Advantages of Transurethral Removal of Certain Bladder Tumors
THE JOURNAL OF UROLOGY
Vol. 73, No. 2, February, 1955 Printed in U.S.A.
ADVANTAGES OF TRANSURETHRAL REMOVAL OF CERTAIN
BLADDER TUMORS GERSHOM J. THOMPSON Section of Urology, Mayo Clinic and Mayo Foundation, Rochester, Minn. AND
JOSEPH H. KAPLAN*
Ever since Beer1 demonstrated that bladder tumors could be entirely destroyed by cystoscopic methods the average urologist has zealously championed this technique. For years it has been thought that the urologist should treat these lesions, not the general surgeon. Some have been very positive in their assertions that most neoplasms of the bladder do not require open surgery, that it is in fact an error so to treat them. Urologists have finally realized that vesical neoplasms are really evidence of a general disease, that they are multicentric in nature and that a visible lesion might be removed while leaving behind other areas of tumor lying below the surface in the opposite wall of the bladder. It certainly seems illogical to open the bladder repeatedly in order to excise tumors. In order to obviate such repetitive procedures some physicians have advocated cystectomy, but radical operation does not attack the root of the problem, for even after removal of the bladder some patients will form growths in their ureters or in the renal pelvis. It has also been shown that, at least in the human, life with an improvised cloaca has certain disadvantages both socially and metabolically. Diverting the urine into the intestine sometimes results in great unhappiness and in general physical and renal deterioration. Urologists have pointed out that in the great majority of cases tumors of low grade can be completely destroyed at the first sitting and subsequent recurrences (really new growths) can be kept under control by interval cystoscopic examination and fulguration. We believe that in the majority of patients who have a high-grade lesion the best treatment available is transurethral excision of all of the grossly visible tumor supplemented when it seems necessary by irradiation. We do not decry cystectomy; in an earlier article 2 a series of cases in which the patients were treated at the Mayo Clinic was described in which cystectomy was performed on 117 patients or 9.6 per cent of 1,222 patients treated during the interval 1946 to 1950 inclusive. It was stated in this article: "We have endeavored to advise this operation for those patients in whom the chance of cure was reasonably good and to employ transurethral operations supplemented with radiation therapy for those patients in whom a tumor appeared too extensive to be treated successfully by cystectomy." The conclusion must not be drawn that all of these Read at annual meeting, American Urological Association, New York, N. Y., June 2, 1954. * Present address: 6333 Wilshire Boulevard, Los Angeles 48, Calif. 1 Beer, Edwin: Removal of neoplasms of the urinary bladder: A new method, employing high-frequency (Oudin) currents through a catheterizing cystoscope. J.A.M.A., 54: 17681769, 1910. 2 Thompson, G. J.: The treatment of cancer of the urinary bladder with particular reference to choice of operation. J. Missouri M.A., 49: 813-817, 1952. 270
BLADDER TUMORS
271
patients in whom small lesions were found were submitted to cystectomy. If there seemed to be a good chance of cure of a small lesion by transurethral excision even though it were of high grade, we often chose this method. The type of operation to be used in any case must hinge on consideration of many factors including such things as the general condition and age of the patient. Other important indications have been discussed previously. 3 Not the least consideration is the comparative immediate morbidity and mortality of the different methods of attack, nor the fact that when a tumor has microscopically extended through the bladder wall the 5-year survival rate following either cystectomy or segmental resection is reduced to 5.2 per cent. 4 This article will discuss a series of 300 cases in which a grade 3 or 4 (Broders' classification) vesical neoplasm was treated at the Mayo Clinic by a transurethral method either alone or in combination with irradiation therapy during the years prior to 1949. The case histories were reviewed and the following pertinent information was recorded: the age and sex of the patient, the location, size, gross appearance and histologic grade of the tumor, the presence or absence of obstruction to the upper part of the urinary tract, the method of treatment employed, treatment of recurrences and the survival period estimated from the time of the initial treatment. The depth of infiltration of the neoplasm into the wall of the bladder was not always recorded. As a matter of fact this is a difficult observation to make and in most cases must be largely a matter of opinion unless tissue is removed from deep in the wall. Fixation of the wall or lack of distensibility, the presence of a filling defect in the cystogram and the firmness of the tissue as noted by feeling it with the end of the cystoscope are all helpful points in estimating the degree of infiltration. In the 300 cases in which high-grade tumor was treated transurethrally, there were 3 hospital deaths. The 5-year survival rates of the 297 remaining patients are recorded in table 1. Approximately 100 other cases of high-grade tumor seen during the same interval were omitted from this study for the following reasons: 1) A segmental resection of the bladder wall or a transvesical removal of a neoplasm had been carried out, either at the clinic or elsmvhere, previously. 2) The transurethral procedure was employed only for the removal of tissue for microscopic study. 3) There was clinical evidence of distant metastasis at the time of the transurethral procedure. 4) There was associated carcinoma of the prostate gland. 5) A transurethral procedure was employed initially and the decision was subsequently made to resort to an open surgical method. The estimated size of the tumors determined by cystoscopic examination varied from 0.5 cm. in diameter to huge lesions that involved almost the entire bladder. Tumors that were located on the base of the bladder, the trigone, the vesical neck, the posterior wall or the dome but accessible to treatment were all included. 3 Thompson, G. J.: Cystoscopic control of vesical neoplasms. In Pack, G. T. and Ariel, I. M.: The Treatment of Cancer and Allied Diseases. Ed. 2, New York: Paul B. Haeber, Inc. (In press.) 4 McDonald, J. R. and Thompson, G. J.: Carcinoma of the urinary bladder: A pathologic study with special reference to invasiveness and vascular invasion. J. Urol., 60: 435-445, 1948.
272
G. J. THOMPSON AND J. H. KAPLAN
TABLE
1. Transurethral removal of malignant neoplasm of the bladder 1948 and
earlier: grades 3 and 4; 5-year survival rates by sex Lived 5 or More Years After Operation
Patients
Sex Total
Traced
Male .. Female.
234 63
218 55
58 29
Total.
297
273
87
I
Survival rate, per cent*
Number
26.6 52.7
I
31.9
* Based on traced patients. Inquiry as of January 1, 1954. Three hospital deaths are excluded in the calculation of survival rates. The fact that a ureteral orifice was encroached on did not influence the decision to employ or not to employ a transurethral method. In fact this study reveals that when a urogram showed evidence of upper-tract obstruction transurethral operation was preferred at the clinic rather than open surgery. In this series of cases of the 164 patients who had excretory urographic study 76 (46.3 per cent) had obstruction of one or both ureters. In the study by Pool and Cook 5 of the urographic findings in a series of patients who underwent open operation there were 42 (36.8 per cent) who had upper urinary tract obstruction, thus indicating a definite trend toward the use of transurethral surgery if ureteral obstruction is present. This comparison of the urographic findings in the two series of cases seems to emphasize the fact that we did not treat what might be termed the best cases by transurethral operation and the worst by open surgery. It must be clearly recognized that the patient often helps to make the decision as to the type of operation performed; some refuse to have radical treatment even when it might appear to the surgeon to be the method of choice. TECHNIQUE OF OPERATION
The excision with a resectoscope of a tumor of the bladder has definite advantages over its excision by open surgical methods. One can carefully remove all of the tumor down into what appears to be normal musculature; resection of any tumor proceeds in orderly fashion, excising the growth down to and below the level of the bladder wall and even excavating tissue until all gross tumor is removed. The surgeon must depend chiefly on gross difference in tissue appearance throughout most of the operation. In most cases the border of the tumor is well defined and its homogeneous gelatinous character coupled with its slightly yellow or gray color contrasts sufficiently with the muscle to provide a reliable guide as to depth and extent of operation. Finally the interlacing bundles of muscle can easily be recognized and it seems that no malignant tissue remains. At this stage additional pieces of tissue are excised from the periphery and depth of the area and examined by frozen-tissue methods. If these are negative, the operation is completed. If, however, the tissue is positive, additional strips 5 Pool, T. L. and Cook, E. N.: Urographic study of the upper part of the urinary tract prior to and after cutaneous ureterostomy and ureterosigmoidostomy. J. Urol., 63: 228-231, 1950.
BLADDER TUMORS
273
can be excised until obviously perivesical tissue including fat is obtained by the excursion of the loop. At this point one must be careful not to overdistend the bladder or extravasation of a serious degree can result. If tumor cells have penetrated the bladder wall it seems logical that radiation must provide whatever additional curative measures are possible. When a tumor which obstructs the ureteral orifice is excised as the intramural portion of the ureter is freed, the end of the ureter will project into the vesical cavity like a nipple or in a fingerlike fashion. The excision by open surgical methods of a tumor obstructing the ureteral orifice usually includes a cuff of normal bladder wall and a portion of healthy ureter; the shortened ureter is then reimplanted into another part of the bladder. These operations have not worked out well. As a rule because of stricture or reflux, the kidney ultimately deteriorates in most instances. In contrast following transurethral segmental resection of such a tumor the ureter is left attached in its normal position and the kidney will often improve remarkably. Hydronephrosis will disappear, and the dilated ureter will recede to almost a normal size. If, however, it has been obstructed for many months or a year or more, the kidney will atrophy but it will usually cause no trouble and will remain as a shriveled structure excreting little if any urine of low specific gravity. VVhen a tumor is located high in the dome or lateral walls or on the anterior wall it is a great aid to have an assistant push down on the abdominal wall (fig. I). This will bring the tumor down so that it can be easily reached. Gentle finger tip control of the instrument will prevent digging too deeply into the vesical wall. It is usually wise to empty the bladder after excision of three or four pieces. For smooth cutting the electrical unit should be set so that the current has minimal coagulating effect. POSTOPERATIVE CARE
The bladder should be drained with a one-way Foley catheter; continuous irrigation is not desirable. If the area from which the growth has been excised is very thin or if it is obvious that the perivesical fat has been exposed it might be wise to use continuous suction on the catheter for the first 48 hours. Some pa-
) Fm. 1. Method of aiding excision of tumor from anterior wall of bladdero
274
G. J. THOMPSON AND J. H. KAPLAN
tients have minimal abdominal pain for a few hours. Catheter drainage should be continued for 5 to 7 days in those cases in which definite perforation of the bladder wall has occurred. Routine use of urinary antiseptics or antibiotics is a wise precaution. RESULTS OF OPERATION
The immediate improvement of bladder function with relief of frequency and cessation of hematuria and tenesmus is quite striking after transurethral operation. This is particularly apparent when an unusually large growth which has encroached on the vesical cavity or immobilized a large segment of the wall has been removed. In a number of cases not included in this series in which exploration in contemplation of cystectomy revealed gross perivesical extension of tumor, a palliative transurethral resection was later performed which added a great deal to the patient's comfort. In a few of them when combined with irradiation therapy the patients survived 2 or 3 years with good bladder function, finally succumbing to metastasis. In our experience this combination of treatment was tolerated better than either permanent cystostomy or cutaneous ureterostomy. The bladder wall heals well following removal of extensive tumors, with surprisingly little scar tissue formation or contracture and with no appreciable reduction of bladder capacity. Apparently the mucosa spreads out and covers the denuded area. Cystoscopy months later will show a smooth, elastic surface. In cases in which the ureteral area has been extensively resected the orifice does not stricture but appears instead as an elliptical opening which can be easily catheterized. In no case has it become necessary at a later date to perform nephrectomy because hydronephrosis developed. One patient, in whom a tumor partially obstructed the left ureteral orifice and required resection of it, developed several years later a primary tumor in the lower third of the right ureter and a nonfunctioning right kidney which necessitated nephro-ureterectomy. His left kidney at that time was functioning normally. It is interesting to speculate whether or not it would now be supporting life if instead of transurethral resection of the initial growth a segmental resection with reimplantation of the ureter had been performed. TABLE
2. Transurethral removal of malignant neoplasm of the bladder 1948 and earlier; 5-year siirvival rate by grade of malignancy (Broders); hospital deaths 3/300 = 1 per cent Patients
Lived 5 or More Years After Operation
Grade
3 4. Total ..
Total
Traced
210 87
194 79
73 14
273
87
297
I
Survival rate,
Number
per cent*
37.6 17.7
I
31. 9
* Based on traced patients. Inquiry as of January 1, 1954. Three hospital deaths are excluded in the calculation of survival rates.
275
BLADDER TUMORS TABLE
3. Transurethral removal of malignant neoplasm of the bladder 1948 and earlier: grades 3 and 4; age-sex distribution Males
Females
Total
Age, years
Number
Per cent
Number
Per cent
Number
Per cent
30-39 40-49 50-59 60-69 70-79 80-89
1 15 49 90
1 6 13 28
10
0.4 6.3 20.7 38.0 30.4 4.2
1.6 9.5 20.6 44.5 20.6 3.2
2 21 62 118 85 12
0.7 7.0 20.7 39.3 28.3 4.0
Total ......
237
100.0
63
100.0
300
Mean ......
72
65.4 years
13
2
I
63 .3 years
I
100.0
65.0 years
There were 3 deaths in the hospital following operation. The ages of these patients, all men, were 76, 76 and 71 years. The cause of death in 1 case was cardiac failure on the seventh postoperative day. In another case one ureteral orifice was completely occluded and the other partially at the time of operation, the blood urea being 76 mg. per 100 cc. The tumor was removed but renal function continued to fail and the patient died on the eighth postoperative day. The third patient died of a stroke on the third postoperative day following removal of a large tumor which completely obstructed one ureteral orifice. Reference to table 1 shows that 31.9 per cent of the traced patients survived 5 years or more. The results in women are about twice as good as in men. The grade of malignancy is listed in table 2 and the age and sex distribution in table 3. It can be noted that 88.3 per cent of the patients were aged from 50 through 79 years. IRRADIATION TREATMENT
Of the 297 patients who survived operation 169 (57 per cent) received supplementary x-ray or radium therapy. In our opinion there were a number of patients in whom residual tumor remained after transurethral operation either in microscopic form or in larger grossly visible areas which were deliberately allowed to remain because excision of the tumor was considered too hazardous. Some of these patients have apparently been cured because repeated cystoscopic examinations have revealed no recurrence over a period of 5 or more years and 1 patient is alive more than 17 years after operation. No attempt will be made in this paper to describe the details of roentgen therapy. In many of the 169 cases radon emanation seeds were implanted. The method and results obtained in a specially studied series have recently been described by Emmett and Winterringer. 6 In studying the urograms obtained during the examination of the 300 patients comprising our series there were many post6 Emmett, J. L. and Winterringer, J. R.: Experience with radon seed implantation for bladder tumors. Read at the meeting of the Southeastern Section of the American Urological Association, Palm Beach, Florida, April 12 to 15, 1954.
276
G. J. THOMPSON AND J. H. KAPLAN
Fm. 2. a, These radon seeds were impla.nted Februa.ry 16, 1946. Note slight pyelo-ureterecta.sis a.ppa.rently due to scar tissue in periureteral a.rea.. b, Showing a.lmost complete regression of ureterecta.sis. Kidney pelvis a.nd ca.lyces now normal in size; radon seeds appear to be well beyond bladder.
operative films which revealed that often radon seeds get out into the perivesical tissues either at the time of implantation or subsequently (fig. 2a and b). As a matter of fact, the deliberate implantation of emanation seeds into the tissues beyond the bladder would not seem amiss because it is in that area that one would like to have some irradiation after the bulk of a growth has been excised with the resectoscope. '\Ve never implant radon seeds into that portion of tumor which projects into the vesical cavity. ILLUSTRATIVE CASES
Case 1.-The patient was a married woman, aged 73 years. On November 1, 1946, a large tumor, which projected into the bladder and superficially infiltrated the region of the right wall including the ureteral orifice, was removed with the Thompson resectoscope. The pathologist reported grade 3 squamous cell epithelioma. There was moderate right ureteropyelectasis, and a definite filling defect could be seen in the excretory cystogram (fig. 3a). Convalescence was uneventful. The patient returned in February 1947, when cystoscopy revealed many recurrences in all of the walls of the bladder. These were destroyed by electrocoagulation, and x-ray therapy was advised. This was subsequently given by a radiologist in her home town. The details of it are not available. In June 1947, a minute area of tumor was destroyed cystoscopically. In January 1948, another small tumor was destroyed but none was found in July. In 1949 several small recurrences were destroyed; an excretory urogram showed definite reduction in the degree of hydronephrosis in the right kidney (fig. 3b). Throughout 1950, 1951 and 1952 on several occasions small tumorsl were destroyed, but in the fall of 1953 at the time of the last examination the bladder was entirely negative.
BLADDER TUMORS
277
FIG. 3. a, Right hydronephrosis; note large filling defect due to grade 3 tumor in right half of bladder. b, Note decrease in size of renal calyces and pelvis.
FIG. 4. a, Right hydronephrosis, hydro-ureter, large filling defect due to grade 4 tumor in right lateral wall and base of bladder. b, Right renal pelvis and calyces now normal in size; cystoscopy showed no recurrence of bladder tumor.
Case 2.-A married woman, aged 89 years, was examined in November 1948, and a tumor 6 by 5 cm. was found in the right posterior and lateral wall of the bladder. The tumor was fl.at and infiltrating in character, but the bladder wall which surrounded it was soft and flexible. The tumor was excised with the loop resectoscope, exposing normal muscle tissue over the whole tumor area. Only the bleeding vessels were electrocoagulated. The tissue was reported by the pathologist to be grade 3 infiltrating squamous cell epithelioma. The patient was
278
G. J. THOMPSON AND J. H. KAPLAN
examined in May 1949 and at intervals since that time and no recurrence has been found. She is now in her ninety-sixth year of life. Case 3. A man, aged 73 years, had a large tumor removed in October 1946. It infiltrated the right side of the trigone, right lateral and anterior wall and extended into the prostatic urethra. The right kidney and ureter showed evidence of obstruction, and there was a large filling defect in the excretory cystogram (fig. 4a). A total of 39 gm. of tissue was excised which the pathologist reported to be grade 4 infiltrating epithelioma. Convalescence from the operation was uneventful. The patient was given a course of five x-ray treatments during the interval October 21 to October 25, 1946. In February 1947, cystoscopic examination showed no evidence of bladder tumor, the right ureteral orifice gaped slightly but spurted clear urine. A urogram showed a normally functioning right kidney (fig. 4b). The patient was examined in July 1947, and in June 1948, without evidence of recurrence. The bladder wall in the region where the tumor had been removed was soft and smooth and distended readily. In October 1948, the patient returned to the clinic with a complaint of urinary difficulty. Cystoscopic examination showed no recurrence of vesical tumor but the prostate was definitely obstructive and 15 gm. of tissue was removed from it which was reported to be grade 4 adenocarcinoma. The patient remained free of urinary symptoms but died of metastasis 1 year later. Case 4.-A married woman, aged 65 years, was found to have a tumor 5 by 6 cm. in size attached by a broad base to the left side of the trigone. It was causing partial obstruction of the left ureteral orifice (fig. 5). On August 25, 1947, the growth was removed with the Thompson resectoscope, going well into the bladder musculature. The tissue was reported to be grade 3 papillary squamous cell
Fm. 5. Large filling defect m left half of bladder due to grade 3 squamous cell epithelioma.
BLADDER TUMORS
279
epithelioma. During convalescence a course of five x-ray treatments was given. The patient has returned at intervals since then and there has never beeu any recurrence of tumor. Case 5. The patient was a man, aged 40 years, from whom a sessile tumor approximately 3 by 4 cm. in size was removed on April 24, 1947. The growth was attached to the right lateral wall and was excised with the Thompson resectoscope. The pathologist reported that the tissue was grade 4 infiltrating keratinizing squamous cell epithelioma. Because of the patient's youth cystectomy was considered but the decision was made not to perform it. He was given a course of seventeen x-ray treatments during the interval April 29 to May I 7, 1947. The patient has had repeated interval cystoscopic examinations since that time and there has never been any recurrence. The last cystoscopy was in January 1954. CONCLUSIONS
vVe believe that urologists have for years pretty well agreed that in the majority of cases tumors of the bladder of low-grade malignancy can be best removed by transurethral methods. As a result of this study and our experience in recent years we have formed the opinion that a tumor of high-grade malignancy which has not infiltrated beyond the bladder wall and which can be accurately delineated is best removed by transurethral operation if such is technically possible. When a tumor has infiltrated into the perivesical tissues or beyond, the transurethral removal of its grossly visible portion follmved by irradiation therapy intended to destroy the microscopic portions which remain is preferable to open operation. vVhen the extent of a tumor of high-grade malignancy cannot be accurately determined with the cystoscope and when tumors of low grade recur ,vith great rapidity both in size and number, transurethral methods of treatment are not advantageous; in such cases cystectomy probably holds more promise of cure. The 5-year survival rate in this series of cases treated by transurethral surgery plus selective irradiation seems better than our results with similar cases which · have been treated by open surgical methods. We believe that transurethral excision of vesical tumors combined with irradiation such as is now available with the cobalt bomb apparatus will in time prove superior to all other methods of treatment which have so far been used.
Vol. 73, No. 2, February, 1955 Printed in U.S.A.
ADVANTAGES OF TRANSURETHRAL REMOVAL OF CERTAIN
BLADDER TUMORS GERSHOM J. THOMPSON Section of Urology, Mayo Clinic and Mayo Foundation, Rochester, Minn. AND
JOSEPH H. KAPLAN*
Ever since Beer1 demonstrated that bladder tumors could be entirely destroyed by cystoscopic methods the average urologist has zealously championed this technique. For years it has been thought that the urologist should treat these lesions, not the general surgeon. Some have been very positive in their assertions that most neoplasms of the bladder do not require open surgery, that it is in fact an error so to treat them. Urologists have finally realized that vesical neoplasms are really evidence of a general disease, that they are multicentric in nature and that a visible lesion might be removed while leaving behind other areas of tumor lying below the surface in the opposite wall of the bladder. It certainly seems illogical to open the bladder repeatedly in order to excise tumors. In order to obviate such repetitive procedures some physicians have advocated cystectomy, but radical operation does not attack the root of the problem, for even after removal of the bladder some patients will form growths in their ureters or in the renal pelvis. It has also been shown that, at least in the human, life with an improvised cloaca has certain disadvantages both socially and metabolically. Diverting the urine into the intestine sometimes results in great unhappiness and in general physical and renal deterioration. Urologists have pointed out that in the great majority of cases tumors of low grade can be completely destroyed at the first sitting and subsequent recurrences (really new growths) can be kept under control by interval cystoscopic examination and fulguration. We believe that in the majority of patients who have a high-grade lesion the best treatment available is transurethral excision of all of the grossly visible tumor supplemented when it seems necessary by irradiation. We do not decry cystectomy; in an earlier article 2 a series of cases in which the patients were treated at the Mayo Clinic was described in which cystectomy was performed on 117 patients or 9.6 per cent of 1,222 patients treated during the interval 1946 to 1950 inclusive. It was stated in this article: "We have endeavored to advise this operation for those patients in whom the chance of cure was reasonably good and to employ transurethral operations supplemented with radiation therapy for those patients in whom a tumor appeared too extensive to be treated successfully by cystectomy." The conclusion must not be drawn that all of these Read at annual meeting, American Urological Association, New York, N. Y., June 2, 1954. * Present address: 6333 Wilshire Boulevard, Los Angeles 48, Calif. 1 Beer, Edwin: Removal of neoplasms of the urinary bladder: A new method, employing high-frequency (Oudin) currents through a catheterizing cystoscope. J.A.M.A., 54: 17681769, 1910. 2 Thompson, G. J.: The treatment of cancer of the urinary bladder with particular reference to choice of operation. J. Missouri M.A., 49: 813-817, 1952. 270
BLADDER TUMORS
271
patients in whom small lesions were found were submitted to cystectomy. If there seemed to be a good chance of cure of a small lesion by transurethral excision even though it were of high grade, we often chose this method. The type of operation to be used in any case must hinge on consideration of many factors including such things as the general condition and age of the patient. Other important indications have been discussed previously. 3 Not the least consideration is the comparative immediate morbidity and mortality of the different methods of attack, nor the fact that when a tumor has microscopically extended through the bladder wall the 5-year survival rate following either cystectomy or segmental resection is reduced to 5.2 per cent. 4 This article will discuss a series of 300 cases in which a grade 3 or 4 (Broders' classification) vesical neoplasm was treated at the Mayo Clinic by a transurethral method either alone or in combination with irradiation therapy during the years prior to 1949. The case histories were reviewed and the following pertinent information was recorded: the age and sex of the patient, the location, size, gross appearance and histologic grade of the tumor, the presence or absence of obstruction to the upper part of the urinary tract, the method of treatment employed, treatment of recurrences and the survival period estimated from the time of the initial treatment. The depth of infiltration of the neoplasm into the wall of the bladder was not always recorded. As a matter of fact this is a difficult observation to make and in most cases must be largely a matter of opinion unless tissue is removed from deep in the wall. Fixation of the wall or lack of distensibility, the presence of a filling defect in the cystogram and the firmness of the tissue as noted by feeling it with the end of the cystoscope are all helpful points in estimating the degree of infiltration. In the 300 cases in which high-grade tumor was treated transurethrally, there were 3 hospital deaths. The 5-year survival rates of the 297 remaining patients are recorded in table 1. Approximately 100 other cases of high-grade tumor seen during the same interval were omitted from this study for the following reasons: 1) A segmental resection of the bladder wall or a transvesical removal of a neoplasm had been carried out, either at the clinic or elsmvhere, previously. 2) The transurethral procedure was employed only for the removal of tissue for microscopic study. 3) There was clinical evidence of distant metastasis at the time of the transurethral procedure. 4) There was associated carcinoma of the prostate gland. 5) A transurethral procedure was employed initially and the decision was subsequently made to resort to an open surgical method. The estimated size of the tumors determined by cystoscopic examination varied from 0.5 cm. in diameter to huge lesions that involved almost the entire bladder. Tumors that were located on the base of the bladder, the trigone, the vesical neck, the posterior wall or the dome but accessible to treatment were all included. 3 Thompson, G. J.: Cystoscopic control of vesical neoplasms. In Pack, G. T. and Ariel, I. M.: The Treatment of Cancer and Allied Diseases. Ed. 2, New York: Paul B. Haeber, Inc. (In press.) 4 McDonald, J. R. and Thompson, G. J.: Carcinoma of the urinary bladder: A pathologic study with special reference to invasiveness and vascular invasion. J. Urol., 60: 435-445, 1948.
272
G. J. THOMPSON AND J. H. KAPLAN
TABLE
1. Transurethral removal of malignant neoplasm of the bladder 1948 and
earlier: grades 3 and 4; 5-year survival rates by sex Lived 5 or More Years After Operation
Patients
Sex Total
Traced
Male .. Female.
234 63
218 55
58 29
Total.
297
273
87
I
Survival rate, per cent*
Number
26.6 52.7
I
31.9
* Based on traced patients. Inquiry as of January 1, 1954. Three hospital deaths are excluded in the calculation of survival rates. The fact that a ureteral orifice was encroached on did not influence the decision to employ or not to employ a transurethral method. In fact this study reveals that when a urogram showed evidence of upper-tract obstruction transurethral operation was preferred at the clinic rather than open surgery. In this series of cases of the 164 patients who had excretory urographic study 76 (46.3 per cent) had obstruction of one or both ureters. In the study by Pool and Cook 5 of the urographic findings in a series of patients who underwent open operation there were 42 (36.8 per cent) who had upper urinary tract obstruction, thus indicating a definite trend toward the use of transurethral surgery if ureteral obstruction is present. This comparison of the urographic findings in the two series of cases seems to emphasize the fact that we did not treat what might be termed the best cases by transurethral operation and the worst by open surgery. It must be clearly recognized that the patient often helps to make the decision as to the type of operation performed; some refuse to have radical treatment even when it might appear to the surgeon to be the method of choice. TECHNIQUE OF OPERATION
The excision with a resectoscope of a tumor of the bladder has definite advantages over its excision by open surgical methods. One can carefully remove all of the tumor down into what appears to be normal musculature; resection of any tumor proceeds in orderly fashion, excising the growth down to and below the level of the bladder wall and even excavating tissue until all gross tumor is removed. The surgeon must depend chiefly on gross difference in tissue appearance throughout most of the operation. In most cases the border of the tumor is well defined and its homogeneous gelatinous character coupled with its slightly yellow or gray color contrasts sufficiently with the muscle to provide a reliable guide as to depth and extent of operation. Finally the interlacing bundles of muscle can easily be recognized and it seems that no malignant tissue remains. At this stage additional pieces of tissue are excised from the periphery and depth of the area and examined by frozen-tissue methods. If these are negative, the operation is completed. If, however, the tissue is positive, additional strips 5 Pool, T. L. and Cook, E. N.: Urographic study of the upper part of the urinary tract prior to and after cutaneous ureterostomy and ureterosigmoidostomy. J. Urol., 63: 228-231, 1950.
BLADDER TUMORS
273
can be excised until obviously perivesical tissue including fat is obtained by the excursion of the loop. At this point one must be careful not to overdistend the bladder or extravasation of a serious degree can result. If tumor cells have penetrated the bladder wall it seems logical that radiation must provide whatever additional curative measures are possible. When a tumor which obstructs the ureteral orifice is excised as the intramural portion of the ureter is freed, the end of the ureter will project into the vesical cavity like a nipple or in a fingerlike fashion. The excision by open surgical methods of a tumor obstructing the ureteral orifice usually includes a cuff of normal bladder wall and a portion of healthy ureter; the shortened ureter is then reimplanted into another part of the bladder. These operations have not worked out well. As a rule because of stricture or reflux, the kidney ultimately deteriorates in most instances. In contrast following transurethral segmental resection of such a tumor the ureter is left attached in its normal position and the kidney will often improve remarkably. Hydronephrosis will disappear, and the dilated ureter will recede to almost a normal size. If, however, it has been obstructed for many months or a year or more, the kidney will atrophy but it will usually cause no trouble and will remain as a shriveled structure excreting little if any urine of low specific gravity. VVhen a tumor is located high in the dome or lateral walls or on the anterior wall it is a great aid to have an assistant push down on the abdominal wall (fig. I). This will bring the tumor down so that it can be easily reached. Gentle finger tip control of the instrument will prevent digging too deeply into the vesical wall. It is usually wise to empty the bladder after excision of three or four pieces. For smooth cutting the electrical unit should be set so that the current has minimal coagulating effect. POSTOPERATIVE CARE
The bladder should be drained with a one-way Foley catheter; continuous irrigation is not desirable. If the area from which the growth has been excised is very thin or if it is obvious that the perivesical fat has been exposed it might be wise to use continuous suction on the catheter for the first 48 hours. Some pa-
) Fm. 1. Method of aiding excision of tumor from anterior wall of bladdero
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G. J. THOMPSON AND J. H. KAPLAN
tients have minimal abdominal pain for a few hours. Catheter drainage should be continued for 5 to 7 days in those cases in which definite perforation of the bladder wall has occurred. Routine use of urinary antiseptics or antibiotics is a wise precaution. RESULTS OF OPERATION
The immediate improvement of bladder function with relief of frequency and cessation of hematuria and tenesmus is quite striking after transurethral operation. This is particularly apparent when an unusually large growth which has encroached on the vesical cavity or immobilized a large segment of the wall has been removed. In a number of cases not included in this series in which exploration in contemplation of cystectomy revealed gross perivesical extension of tumor, a palliative transurethral resection was later performed which added a great deal to the patient's comfort. In a few of them when combined with irradiation therapy the patients survived 2 or 3 years with good bladder function, finally succumbing to metastasis. In our experience this combination of treatment was tolerated better than either permanent cystostomy or cutaneous ureterostomy. The bladder wall heals well following removal of extensive tumors, with surprisingly little scar tissue formation or contracture and with no appreciable reduction of bladder capacity. Apparently the mucosa spreads out and covers the denuded area. Cystoscopy months later will show a smooth, elastic surface. In cases in which the ureteral area has been extensively resected the orifice does not stricture but appears instead as an elliptical opening which can be easily catheterized. In no case has it become necessary at a later date to perform nephrectomy because hydronephrosis developed. One patient, in whom a tumor partially obstructed the left ureteral orifice and required resection of it, developed several years later a primary tumor in the lower third of the right ureter and a nonfunctioning right kidney which necessitated nephro-ureterectomy. His left kidney at that time was functioning normally. It is interesting to speculate whether or not it would now be supporting life if instead of transurethral resection of the initial growth a segmental resection with reimplantation of the ureter had been performed. TABLE
2. Transurethral removal of malignant neoplasm of the bladder 1948 and earlier; 5-year siirvival rate by grade of malignancy (Broders); hospital deaths 3/300 = 1 per cent Patients
Lived 5 or More Years After Operation
Grade
3 4. Total ..
Total
Traced
210 87
194 79
73 14
273
87
297
I
Survival rate,
Number
per cent*
37.6 17.7
I
31. 9
* Based on traced patients. Inquiry as of January 1, 1954. Three hospital deaths are excluded in the calculation of survival rates.
275
BLADDER TUMORS TABLE
3. Transurethral removal of malignant neoplasm of the bladder 1948 and earlier: grades 3 and 4; age-sex distribution Males
Females
Total
Age, years
Number
Per cent
Number
Per cent
Number
Per cent
30-39 40-49 50-59 60-69 70-79 80-89
1 15 49 90
1 6 13 28
10
0.4 6.3 20.7 38.0 30.4 4.2
1.6 9.5 20.6 44.5 20.6 3.2
2 21 62 118 85 12
0.7 7.0 20.7 39.3 28.3 4.0
Total ......
237
100.0
63
100.0
300
Mean ......
72
65.4 years
13
2
I
63 .3 years
I
100.0
65.0 years
There were 3 deaths in the hospital following operation. The ages of these patients, all men, were 76, 76 and 71 years. The cause of death in 1 case was cardiac failure on the seventh postoperative day. In another case one ureteral orifice was completely occluded and the other partially at the time of operation, the blood urea being 76 mg. per 100 cc. The tumor was removed but renal function continued to fail and the patient died on the eighth postoperative day. The third patient died of a stroke on the third postoperative day following removal of a large tumor which completely obstructed one ureteral orifice. Reference to table 1 shows that 31.9 per cent of the traced patients survived 5 years or more. The results in women are about twice as good as in men. The grade of malignancy is listed in table 2 and the age and sex distribution in table 3. It can be noted that 88.3 per cent of the patients were aged from 50 through 79 years. IRRADIATION TREATMENT
Of the 297 patients who survived operation 169 (57 per cent) received supplementary x-ray or radium therapy. In our opinion there were a number of patients in whom residual tumor remained after transurethral operation either in microscopic form or in larger grossly visible areas which were deliberately allowed to remain because excision of the tumor was considered too hazardous. Some of these patients have apparently been cured because repeated cystoscopic examinations have revealed no recurrence over a period of 5 or more years and 1 patient is alive more than 17 years after operation. No attempt will be made in this paper to describe the details of roentgen therapy. In many of the 169 cases radon emanation seeds were implanted. The method and results obtained in a specially studied series have recently been described by Emmett and Winterringer. 6 In studying the urograms obtained during the examination of the 300 patients comprising our series there were many post6 Emmett, J. L. and Winterringer, J. R.: Experience with radon seed implantation for bladder tumors. Read at the meeting of the Southeastern Section of the American Urological Association, Palm Beach, Florida, April 12 to 15, 1954.
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G. J. THOMPSON AND J. H. KAPLAN
Fm. 2. a, These radon seeds were impla.nted Februa.ry 16, 1946. Note slight pyelo-ureterecta.sis a.ppa.rently due to scar tissue in periureteral a.rea.. b, Showing a.lmost complete regression of ureterecta.sis. Kidney pelvis a.nd ca.lyces now normal in size; radon seeds appear to be well beyond bladder.
operative films which revealed that often radon seeds get out into the perivesical tissues either at the time of implantation or subsequently (fig. 2a and b). As a matter of fact, the deliberate implantation of emanation seeds into the tissues beyond the bladder would not seem amiss because it is in that area that one would like to have some irradiation after the bulk of a growth has been excised with the resectoscope. '\Ve never implant radon seeds into that portion of tumor which projects into the vesical cavity. ILLUSTRATIVE CASES
Case 1.-The patient was a married woman, aged 73 years. On November 1, 1946, a large tumor, which projected into the bladder and superficially infiltrated the region of the right wall including the ureteral orifice, was removed with the Thompson resectoscope. The pathologist reported grade 3 squamous cell epithelioma. There was moderate right ureteropyelectasis, and a definite filling defect could be seen in the excretory cystogram (fig. 3a). Convalescence was uneventful. The patient returned in February 1947, when cystoscopy revealed many recurrences in all of the walls of the bladder. These were destroyed by electrocoagulation, and x-ray therapy was advised. This was subsequently given by a radiologist in her home town. The details of it are not available. In June 1947, a minute area of tumor was destroyed cystoscopically. In January 1948, another small tumor was destroyed but none was found in July. In 1949 several small recurrences were destroyed; an excretory urogram showed definite reduction in the degree of hydronephrosis in the right kidney (fig. 3b). Throughout 1950, 1951 and 1952 on several occasions small tumorsl were destroyed, but in the fall of 1953 at the time of the last examination the bladder was entirely negative.
BLADDER TUMORS
277
FIG. 3. a, Right hydronephrosis; note large filling defect due to grade 3 tumor in right half of bladder. b, Note decrease in size of renal calyces and pelvis.
FIG. 4. a, Right hydronephrosis, hydro-ureter, large filling defect due to grade 4 tumor in right lateral wall and base of bladder. b, Right renal pelvis and calyces now normal in size; cystoscopy showed no recurrence of bladder tumor.
Case 2.-A married woman, aged 89 years, was examined in November 1948, and a tumor 6 by 5 cm. was found in the right posterior and lateral wall of the bladder. The tumor was fl.at and infiltrating in character, but the bladder wall which surrounded it was soft and flexible. The tumor was excised with the loop resectoscope, exposing normal muscle tissue over the whole tumor area. Only the bleeding vessels were electrocoagulated. The tissue was reported by the pathologist to be grade 3 infiltrating squamous cell epithelioma. The patient was
278
G. J. THOMPSON AND J. H. KAPLAN
examined in May 1949 and at intervals since that time and no recurrence has been found. She is now in her ninety-sixth year of life. Case 3. A man, aged 73 years, had a large tumor removed in October 1946. It infiltrated the right side of the trigone, right lateral and anterior wall and extended into the prostatic urethra. The right kidney and ureter showed evidence of obstruction, and there was a large filling defect in the excretory cystogram (fig. 4a). A total of 39 gm. of tissue was excised which the pathologist reported to be grade 4 infiltrating epithelioma. Convalescence from the operation was uneventful. The patient was given a course of five x-ray treatments during the interval October 21 to October 25, 1946. In February 1947, cystoscopic examination showed no evidence of bladder tumor, the right ureteral orifice gaped slightly but spurted clear urine. A urogram showed a normally functioning right kidney (fig. 4b). The patient was examined in July 1947, and in June 1948, without evidence of recurrence. The bladder wall in the region where the tumor had been removed was soft and smooth and distended readily. In October 1948, the patient returned to the clinic with a complaint of urinary difficulty. Cystoscopic examination showed no recurrence of vesical tumor but the prostate was definitely obstructive and 15 gm. of tissue was removed from it which was reported to be grade 4 adenocarcinoma. The patient remained free of urinary symptoms but died of metastasis 1 year later. Case 4.-A married woman, aged 65 years, was found to have a tumor 5 by 6 cm. in size attached by a broad base to the left side of the trigone. It was causing partial obstruction of the left ureteral orifice (fig. 5). On August 25, 1947, the growth was removed with the Thompson resectoscope, going well into the bladder musculature. The tissue was reported to be grade 3 papillary squamous cell
Fm. 5. Large filling defect m left half of bladder due to grade 3 squamous cell epithelioma.
BLADDER TUMORS
279
epithelioma. During convalescence a course of five x-ray treatments was given. The patient has returned at intervals since then and there has never beeu any recurrence of tumor. Case 5. The patient was a man, aged 40 years, from whom a sessile tumor approximately 3 by 4 cm. in size was removed on April 24, 1947. The growth was attached to the right lateral wall and was excised with the Thompson resectoscope. The pathologist reported that the tissue was grade 4 infiltrating keratinizing squamous cell epithelioma. Because of the patient's youth cystectomy was considered but the decision was made not to perform it. He was given a course of seventeen x-ray treatments during the interval April 29 to May I 7, 1947. The patient has had repeated interval cystoscopic examinations since that time and there has never been any recurrence. The last cystoscopy was in January 1954. CONCLUSIONS
vVe believe that urologists have for years pretty well agreed that in the majority of cases tumors of the bladder of low-grade malignancy can be best removed by transurethral methods. As a result of this study and our experience in recent years we have formed the opinion that a tumor of high-grade malignancy which has not infiltrated beyond the bladder wall and which can be accurately delineated is best removed by transurethral operation if such is technically possible. When a tumor has infiltrated into the perivesical tissues or beyond, the transurethral removal of its grossly visible portion follmved by irradiation therapy intended to destroy the microscopic portions which remain is preferable to open operation. vVhen the extent of a tumor of high-grade malignancy cannot be accurately determined with the cystoscope and when tumors of low grade recur ,vith great rapidity both in size and number, transurethral methods of treatment are not advantageous; in such cases cystectomy probably holds more promise of cure. The 5-year survival rate in this series of cases treated by transurethral surgery plus selective irradiation seems better than our results with similar cases which · have been treated by open surgical methods. We believe that transurethral excision of vesical tumors combined with irradiation such as is now available with the cobalt bomb apparatus will in time prove superior to all other methods of treatment which have so far been used.