Scandinavian Journal of Urology and Nephrology
ISSN: 0036-5599 (Print) 1651-2065 (Online) Journal homepage: http://www.tandfonline.com/loi/isju19
Epodyl® Treatment of Bladder Tumours H. V. Nielsen & E. Thybo To cite this article: H. V. Nielsen & E. Thybo (1979) Epodyl® Treatment of Bladder Tumours, Scandinavian Journal of Urology and Nephrology, 13:1, 59-63, DOI: 10.3109/00365597909180000 To link to this article: http://dx.doi.org/10.3109/00365597909180000
Published online: 15 Feb 2010.
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Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isju19 Download by: [University of California Santa Barbara]
Date: 23 March 2016, At: 16:36
Scand J Urol Nephrol 13: 59-63, 1979
EPODYL@TREATMENT OF BLADDER TUMOURS H. V. Nielsen and E. Thybo
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
(Submitted for publication April 10. 1976)
Multiple, non-invasive bladder papillomas were treated with intravesical instillation of EpodyP in 44 patients. Irritative cystitis occurred in 16 per cent of the series, and in these cases Epodylm treatment had to be stopped. Total or partial disappearance of the papillomas was seen after 16 months of treatment in 43% of the total series. This was the minimum success rate, since all the patients who left the study were counted as failures. When the treatment could be camied through, total or partial disappearance of papillomas occurred in 19 of 29 patients (66%). EpodyP has a place in the treatment of vesical papillomas when other methods have failed. Ahstrrict.
The management of benign multiple papillomas of the urinary bladder is often rendered difficult by the numerous electrocoagulations that are required, sometimes in combination with cystostomy for excision of large papillomatous masses. Other methods of treatment, such as external irradiation and intracavitary radium insertion, frequently give distressing symptoms in the form of irradiation colitis or irradiation cystitis with risk of contracted bladder (Jones & Swinney, 1961). Cystectomy in such a relatively benign disorder is restrictively undertaken. unless there is massive extension to the urethra. Intravesical instillation of various chemical solutions has been used to treat bladder papillomas for many years. Podophyllin, silver nitrate and colloidal solutions of radioactive gold or arsenic are among these substances. No convincing benefits have been demonstrated and troublesome sideeffects frequently arise (Abbassian & Wallace, 1966). Intracavitary thio-TEPA has been tried in recurrent papillomatosis since 1961 (Editorial, 1976; Veenema, Dean, Roberts, Fingerhut, Chowhury & Tarassoly, 1962; Oravisto. 1972). The effect on papillomas has been reasonably good, but was frequently accompanied by deleterious action on the bone marrow after absorption, through the bladder
wall. There was also a high incidence of local irritation. EpodyP instilled into the bladder was reported by Riddle & Wallace (1971) to have a favourable action on papillomatous tumours. These writers found fewer side-effects than after administration of thio-TEPA. Epodyl@is a triethylene glycol di-glycerol ether. Its molecular weight is 262, whereas that of thioTEPA is 189. The difference in molecular weight was thought to explain the lessor absorption of EpodyP via the bladder mucosa and thereby also the milder systemic effects (Riddle, 1973).
METHODS Treatment is on an out-patient basis. The bladder is emptied with a disposable catheter and 100 ml I % EpodyP solution is instilled. The patient is told not to pass urine for one hour. The Epodyl" solution is prepared immediately before the instillation. Unlike Riddle, we d o not instruct the patients to roll around in different positions. They are ambulant during the hour that Epodyl@is in the bladder. At the end of this time the urine is naturally voided. EpodyP treatment is not given until two to three weeks after electrocoagulation or other intravesical manipulations that can damage the mucosa. The treatment consists of three sequences-courses 1 . 2 and 3. Course I consists of intravesical instillation of Epodyla once a week for 12 weeks, with cystoscopy in the 13th week. If the treatment is effective. by which we mean that all or more than half of the tumour has disappeared, course 2 is undertaken. Course, 2 comprises Epodyl" instillation once monthly for 12 months with cystoscopy every third month. If course 2 is effective, the patient proceeds to course 3. Coursc~ 3 is EpodyF instillation once every three months, with cystoscopy every fourth month. Haematologic checks are made (particularly of leukocytes and thrombocytes) in connexion with each EpodyP treatment. At each cystoscopic check-up, urine is sampled for culture and cytologic examination.
60
H . V . Niclsoti iitid E. TIiybo
Table I. Sex. trgr cind dicrtition of’swnptotns tit sttirt o f E p o d y l a trrtitment Duration of symptoms (years)
Age
No. of patients
Mean
Range
5
2
3
15
10
5 9
13
14
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
Table 11. Result o f trccitrnrnt in rrltition t o histologic grtide c~fptipillomtrto.si.s(it .sttrrt biopsy Histologic grading (Bergquist et al.) Result
1
2 (1
2h
Total tumour disappearance Partial tumour disappearance N o effect, or patient left the study Total
-
II 2 13 26
-
-
RESULTS Between March 1973 and March 1975 we treated 44 patients with EpodyP. Ten were women and 34 men and their respective mean ages were 66 and 67 years. The age and sex distribution in relation to known duration of papillomatosis is shown in Table I . More than 60% of the patients had a history of symptoms for more than two years. Histologic classification of papilloma was made in all cases before treatment was begun. using the system recommended by Bergquist, Ljungquist & Moberger (1965). N o patient with invasive tumor was accepted for Epodyl@treatment. N o relation-
3
5 I
-
4 4
Extent of papillomatosis
Total
-
16
7
I
13
1
3 25 44
ship was found between histologic grade at the initial biopsy and the result of treatment (Table 11). The extent of papillomatosis at the start of treatment is compared in Table I 1 1 with the frequency of participation in treatment courses. In the patients with only a few papillomas. electrocoagulation had been carried out shortly before E p o d y P treatment was begun. In all cases electrocoagulation had been tried for a long time before Epodyl@was given. During the 12 weeks of course I , treatment had to be stopped in eight of the 44 patients. The reason in six cases was severe symptoms of bladder irritation. One patient was too senile to co-operate. The eighth patient had haematuria during E p o d y P treatment, but he also had Osler’s disease.
Course 2
Course 1 No. of patients
Not clessifiable
Not completed
Completed, Not but course 2 comnot commenced pleted
Courses 1 and 2 Completed
-
2
9
I 2
8
1
4 3
5
3
-
1
1
44
8
7
6
23
Less than 3 papillomas More than 3 papillomas Diffuse papillomatosis Cystoscopy not classifiable
16
1 3
11
Total
12
5
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
Left the study
Partial effect
effect
4
6 3
23 16
11
3
I6
No effect
Course no.
No. of patient\
1
44 29
U
I
-7
6
Total
44
14
The cystoscopic findings at the end of course I are summarized in Table IV. Of the 36 patients who completed the course, seven showed no tumour diminution and were therefore excluded from further treatment. Some effect, i.e. more than halving of the tumour. was seen in six cases. The remaining 23 patients were tumour-free in the 13th week after starting Epodyl" treatment. Course 2 was therefore begun by 29 patients, 23 with full and six with partial effect of course I . Six of the 29 patients left the series during course 3, three of them when invasion was demonstrated by biopsy (all three had had partial effect from course 1). One patient died of cerebral thrombosis, one had severe symptoms of bladder irritation and the sixth patient refused further treatment. Course 2 was completed by 23 patients (Table IV). In four of them course 2 had no effect on the tumour and in three there was only some effect. Complete disappearance of papilloma was obtained in 16 cases. The patients with good results from course 2 began course 3, with installation of Epodyla every third month. The results of this course are not yet available. The duration of symptoms before EpodylE treatment is correlated with the result of this treatment in Table V . There seemed to be a tendency to more Table VI. Reported
Full
Result
2-5
>5
4
5
7
16
-
2
1
3
Total tumour disappearance Partial tumour disappearance No effect. or left the study
14
S
6
25
Total
18
12
14
44
frequent effect with longer duration of symptoms. Conversely. relatively many of the patients who left the study, or in whom Epodyl@ was ineffective, were among those with the shortest duration of symptoms. The haematologic parameters were unaffected during the period of Epody16 treatment.
DISCUSSION The indications for EpodyP treatment in the 44 patients of this series were similar to those described by Riddle & Wallace. and by Riddle. i Y z .
resir1t.s o f E p o d y P treutment
Series and observation time
No. of cases at start of trial No. of cases at time of report Total tumour disappearance Partial tumour disappearance No effect of treatment Left the study. or inadequate observation time
Total
ISSN: 0036-5599 (Print) 1651-2065 (Online) Journal homepage: http://www.tandfonline.com/loi/isju19
Epodyl® Treatment of Bladder Tumours H. V. Nielsen & E. Thybo To cite this article: H. V. Nielsen & E. Thybo (1979) Epodyl® Treatment of Bladder Tumours, Scandinavian Journal of Urology and Nephrology, 13:1, 59-63, DOI: 10.3109/00365597909180000 To link to this article: http://dx.doi.org/10.3109/00365597909180000
Published online: 15 Feb 2010.
Submit your article to this journal
View related articles
Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isju19 Download by: [University of California Santa Barbara]
Date: 23 March 2016, At: 16:36
Scand J Urol Nephrol 13: 59-63, 1979
EPODYL@TREATMENT OF BLADDER TUMOURS H. V. Nielsen and E. Thybo
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
(Submitted for publication April 10. 1976)
Multiple, non-invasive bladder papillomas were treated with intravesical instillation of EpodyP in 44 patients. Irritative cystitis occurred in 16 per cent of the series, and in these cases Epodylm treatment had to be stopped. Total or partial disappearance of the papillomas was seen after 16 months of treatment in 43% of the total series. This was the minimum success rate, since all the patients who left the study were counted as failures. When the treatment could be camied through, total or partial disappearance of papillomas occurred in 19 of 29 patients (66%). EpodyP has a place in the treatment of vesical papillomas when other methods have failed. Ahstrrict.
The management of benign multiple papillomas of the urinary bladder is often rendered difficult by the numerous electrocoagulations that are required, sometimes in combination with cystostomy for excision of large papillomatous masses. Other methods of treatment, such as external irradiation and intracavitary radium insertion, frequently give distressing symptoms in the form of irradiation colitis or irradiation cystitis with risk of contracted bladder (Jones & Swinney, 1961). Cystectomy in such a relatively benign disorder is restrictively undertaken. unless there is massive extension to the urethra. Intravesical instillation of various chemical solutions has been used to treat bladder papillomas for many years. Podophyllin, silver nitrate and colloidal solutions of radioactive gold or arsenic are among these substances. No convincing benefits have been demonstrated and troublesome sideeffects frequently arise (Abbassian & Wallace, 1966). Intracavitary thio-TEPA has been tried in recurrent papillomatosis since 1961 (Editorial, 1976; Veenema, Dean, Roberts, Fingerhut, Chowhury & Tarassoly, 1962; Oravisto. 1972). The effect on papillomas has been reasonably good, but was frequently accompanied by deleterious action on the bone marrow after absorption, through the bladder
wall. There was also a high incidence of local irritation. EpodyP instilled into the bladder was reported by Riddle & Wallace (1971) to have a favourable action on papillomatous tumours. These writers found fewer side-effects than after administration of thio-TEPA. Epodyl@is a triethylene glycol di-glycerol ether. Its molecular weight is 262, whereas that of thioTEPA is 189. The difference in molecular weight was thought to explain the lessor absorption of EpodyP via the bladder mucosa and thereby also the milder systemic effects (Riddle, 1973).
METHODS Treatment is on an out-patient basis. The bladder is emptied with a disposable catheter and 100 ml I % EpodyP solution is instilled. The patient is told not to pass urine for one hour. The Epodyl" solution is prepared immediately before the instillation. Unlike Riddle, we d o not instruct the patients to roll around in different positions. They are ambulant during the hour that Epodyl@is in the bladder. At the end of this time the urine is naturally voided. EpodyP treatment is not given until two to three weeks after electrocoagulation or other intravesical manipulations that can damage the mucosa. The treatment consists of three sequences-courses 1 . 2 and 3. Course I consists of intravesical instillation of Epodyla once a week for 12 weeks, with cystoscopy in the 13th week. If the treatment is effective. by which we mean that all or more than half of the tumour has disappeared, course 2 is undertaken. Course, 2 comprises Epodyl" instillation once monthly for 12 months with cystoscopy every third month. If course 2 is effective, the patient proceeds to course 3. Coursc~ 3 is EpodyF instillation once every three months, with cystoscopy every fourth month. Haematologic checks are made (particularly of leukocytes and thrombocytes) in connexion with each EpodyP treatment. At each cystoscopic check-up, urine is sampled for culture and cytologic examination.
60
H . V . Niclsoti iitid E. TIiybo
Table I. Sex. trgr cind dicrtition of’swnptotns tit sttirt o f E p o d y l a trrtitment Duration of symptoms (years)
Age
No. of patients
Mean
Range
5
2
3
15
10
5 9
13
14
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
Table 11. Result o f trccitrnrnt in rrltition t o histologic grtide c~fptipillomtrto.si.s(it .sttrrt biopsy Histologic grading (Bergquist et al.) Result
1
2 (1
2h
Total tumour disappearance Partial tumour disappearance N o effect, or patient left the study Total
-
II 2 13 26
-
-
RESULTS Between March 1973 and March 1975 we treated 44 patients with EpodyP. Ten were women and 34 men and their respective mean ages were 66 and 67 years. The age and sex distribution in relation to known duration of papillomatosis is shown in Table I . More than 60% of the patients had a history of symptoms for more than two years. Histologic classification of papilloma was made in all cases before treatment was begun. using the system recommended by Bergquist, Ljungquist & Moberger (1965). N o patient with invasive tumor was accepted for Epodyl@treatment. N o relation-
3
5 I
-
4 4
Extent of papillomatosis
Total
-
16
7
I
13
1
3 25 44
ship was found between histologic grade at the initial biopsy and the result of treatment (Table 11). The extent of papillomatosis at the start of treatment is compared in Table I 1 1 with the frequency of participation in treatment courses. In the patients with only a few papillomas. electrocoagulation had been carried out shortly before E p o d y P treatment was begun. In all cases electrocoagulation had been tried for a long time before Epodyl@was given. During the 12 weeks of course I , treatment had to be stopped in eight of the 44 patients. The reason in six cases was severe symptoms of bladder irritation. One patient was too senile to co-operate. The eighth patient had haematuria during E p o d y P treatment, but he also had Osler’s disease.
Course 2
Course 1 No. of patients
Not clessifiable
Not completed
Completed, Not but course 2 comnot commenced pleted
Courses 1 and 2 Completed
-
2
9
I 2
8
1
4 3
5
3
-
1
1
44
8
7
6
23
Less than 3 papillomas More than 3 papillomas Diffuse papillomatosis Cystoscopy not classifiable
16
1 3
11
Total
12
5
Downloaded by [University of California Santa Barbara] at 16:36 23 March 2016
Left the study
Partial effect
effect
4
6 3
23 16
11
3
I6
No effect
Course no.
No. of patient\
1
44 29
U
I
-7
6
Total
44
14
The cystoscopic findings at the end of course I are summarized in Table IV. Of the 36 patients who completed the course, seven showed no tumour diminution and were therefore excluded from further treatment. Some effect, i.e. more than halving of the tumour. was seen in six cases. The remaining 23 patients were tumour-free in the 13th week after starting Epodyl" treatment. Course 2 was therefore begun by 29 patients, 23 with full and six with partial effect of course I . Six of the 29 patients left the series during course 3, three of them when invasion was demonstrated by biopsy (all three had had partial effect from course 1). One patient died of cerebral thrombosis, one had severe symptoms of bladder irritation and the sixth patient refused further treatment. Course 2 was completed by 23 patients (Table IV). In four of them course 2 had no effect on the tumour and in three there was only some effect. Complete disappearance of papilloma was obtained in 16 cases. The patients with good results from course 2 began course 3, with installation of Epodyla every third month. The results of this course are not yet available. The duration of symptoms before EpodylE treatment is correlated with the result of this treatment in Table V . There seemed to be a tendency to more Table VI. Reported
Full
Result
2-5
>5
4
5
7
16
-
2
1
3
Total tumour disappearance Partial tumour disappearance No effect. or left the study
14
S
6
25
Total
18
12
14
44
frequent effect with longer duration of symptoms. Conversely. relatively many of the patients who left the study, or in whom Epodyl@ was ineffective, were among those with the shortest duration of symptoms. The haematologic parameters were unaffected during the period of Epody16 treatment.
DISCUSSION The indications for EpodyP treatment in the 44 patients of this series were similar to those described by Riddle & Wallace. and by Riddle. i Y z .
resir1t.s o f E p o d y P treutment
Series and observation time
No. of cases at start of trial No. of cases at time of report Total tumour disappearance Partial tumour disappearance No effect of treatment Left the study. or inadequate observation time
Total
