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Vesicoureteral Reflux After Transurethral Resection of Bladder Tumors

Mircea Teodorescu Brnzeu
Petre Drăgan

Department of Urology

Victor Babes University of Medicine and Pharmacy Timisoara


INTRODUCTION

The development of endoscopic surgery in the treatment of superficial bladder tumors allowed the control of these tumors in a great number of patients with a high tendency of recurrence due to repeated transurethral endoscopic resections.

The advantages of transurethral resection are emphasized: reduced operational stress, early mobilization, quick removal of the catheter, low cost of nursing. Therefore the operation is given preference mainly in the treatment of elderly patients with bladder tumor.1

This treatment is not devoid of minor or major secondary effects such as hematuria, infection, enuresis2, the perforation of the bladder wall, intraperitoneal and extraperitoneal perforations, strictures of urethra and/or bladder neck, ureteric stenosis 3 and vesicoureteral reflux.

Radical, full-thickness resection of the bladder wall and overlying bladder tumor is a management option in highly selected patients with muscle invasive bladder cancer. The resection of tumors localized in the trigone of bladder and close to the ureteric orifice may cause the damage of Bells muscle and may alter the antireflux valvular mechanism.4

Reflux can be associated with ureterotrigonal abnormalities such as paraureteric diverticulum, complete duplication of the ureter and gaping ureteric orifice, and it can be diagnosed before the bladder tumour treatment.5

Patients treated with transurethral slitting of the ureteral orifice for a stone at the distal end of the ureter or a ureterocele can show vesicoureteral reflux previous to bladder tumor resection. 6

Morita and Tokue reported a case of vesicoureteral reflux 3 years after intravesical instillation of bacillus Calmette-Guerin against carcinoma in situ of the bladder. 7

Vesicoureteral reflux after transurethral resection of bladder tumors is a significant complication. Some of the patients with such reflux suffer no apparent ill effects. Others can develop urinary infection, hydronephrosis, nephrotic syndrome, chronic renal failure. A higher risk of upper urinary tract cancer must be expected in cases of multiple primary superficial bladder tumors and vesicoureteral reflux after transurethral resection of bladder tumors. 8

We have the obligation to recognize the reflux when it exists and treat it proper with antirefluxing ureteric reimplantation (ureterocystoneostomies) or by polytetrafluoroethylene (Teflon) injections. 9


MATERIAL AND METHOD

The aim of this study was to highlight the vesicoureteral reflux in patients who had removed one or more bladder tumors situated in the neighbourhood of the ureteric orifice and the trigone of bladder.10 The object of study were patients with bladder tumors who had no other kind of vesicoureteral reflux diagnosed before endoscopic resection11.

The evaluation of the patients included intravenous pyelography, voiding cystography, abdominal radiography, cystoscopy and serum creatinine determination.

In the 11 patients surveyed, the periodical cystoscopic control highlighted an abnormal localization of one or both ureteric orifices, situated sideways, most frequently with a large orifice and a damaged antireflux mechanism. The length of the submucosal ureter, the orifice configuration and its location as well as the trigonal muscular development are parameters evaluated endoscopically.

Ultrasonography was performed to all patient because it is safe, easily available, cost effective and provides images of both upper and lower renal tract. It helped us to diagnose recurrence of bladder tumors and changes in the bladder wall. Data about sizes of the kidney and renal parenchyma, as well as about the status of upper-collecting system were gathered. It is recommended to use ultrasonography as the initial radiological investigation for detection of bladder carcinomas in patients presenting hematuria. 12 Ultrasonography was more sensitive in clarifying the pathology in upper renal tracts when urography failed due to none or poor excretion of contrast substance.

A standard voiding cystourethrography was obtained by instilling radiopaque contrast medium into the bladder and imaging the bladder and renal fossae during filling and voiding. The voiding cystography highlighted both the vesicoureteral reflux and the degree of reflux. Reflux occurs in varying degrees of severity ranging from Grade I to Grade V, with Grade I being the least severe and Grade V being the most severe.

Grade I reflux does not reach the renal pelvis. Grade II reflux reaches the renal pelvis, without the dilatation of the collectiong system. Grade III reflux produces moderate dilatation of the ureter, mild dilatation of the collecting system, minimally deformed fornices. Grade IV reflux causes moderate dilatation of the ureter, moderate dilatation of the collecting system, blunt fornices and impressions of the papillae. Grade V reflux produces gross dilatation and kinking of the ureter, market dilatation of the collecting system, papillary impressions no longer visibile and intraparenchymal reflux.

The magnetic resonance voiding cystography compared with voiding cystourethrography for detecting and grading vesicoureteral reflux (VUR) is less sensitivit for bladder reflux13. Our patients didnot undergo resonance voiding cystography.

An intravenous pyelogram was performed to detect possible problems of the kidneys, ureters, and bladder. An non-iodine containing contrast medium is given by intravenous injection. A series of abdominal radiographs are taken at the time of injection, at measured times afterwards, and after the patient has voided.

The urography helped determine the renal function and the morphology of the entire upper urinary system. Intravenous pyelography showed the size, shape, and position of the urinary tract, and it evaluated the collecting system inside the kidneys. We followed the implantation of the ureter in the urinary bladder wall.


RESULTS

64% of the patients investigated were men and 36% women. The mean age of the patients was 74.8 years, including an age range 53 to 80. Only one tumor was observed in 63%, of which 57% had a large tumor. In 36% several bladder tumors were revealed after cystoscopy. 27.2% underwent no surgical intervention prior to the endoscopic resection which altered the antireflux mechanism. 45.4% had several transbladder resections for bladder tumors, 18.2% had a transurethral resection of the bladder tumour, and 9.2% had partial cystectomy.

Unilateral urethral reflux was diagnosed in 72.7% of patients and bilateral in 9.2%. In 2 patients (19.1%) no vesicoureteral reflux was noticed after cystography although cystoscopic investigation highlighted a large urethral orifice, in a lateral position.

An equal number of patients with reflux on the right and on left side was noticed.

Grade I reflux was present in 27.2% of the patients under study, grade II reflux in 45.4%, and a massive reflux with reduction of renal parenchyma (grade IV) in 9.1% of patients.



Fig.1.Grade I Vesicoureteral Reflux: urine refluxes part-way up the ureter



Fig.2 Grade IV Vesicoureteral Reflux: urine refluxes all the way up the ureter with marked dilatation of the ureter and calyces.

The renal and urethral modifications caused by bladder-urethral reflux were highlighted with the help of imagistic investigation ( ecography and urography) which showed pyelonephritic modifications in 36.3% of the investigated patients.14

Analysing the degree of tumoral invasion in the bladder, one can reach the following conclusions: in 45.5% of patients the tumor invaded the internal elastic subepithelial connective tissue (T1), in 27.3% an invasion of the superficial muscle was noticed, while in 27.2% the external half of the bladder wall was invaded (T3).



DISCUSSION AND CONCLUSION

Endoscopic surgery of bladder tumors requires a radical attitude which implies the resection of the deep muscular layer, giving the anatomo-pathologist the possibility of differentiating the superficial tumors from the infiltrative ones. The adequate treatment can be followed according to the nature of the tumor. Bladder-urethral reflux may appear during the multimodal therapy of the bladder tumor.

Mukamel et al. 15 mention a low incidence of bladder-urethral reflux in the case of tumors with trigonal localization (17.3%), while tumors within the immediate neighbourhood of urethral orifices have an incidence of 24%. The authors consider this situation to be the result of fibrosis and inflammatory phenomena after instillations with Thiotepa over a longer period of time in the patients under investigation.

The study undertaken by Ricos Torrent et al. 16 shows the existence of bladder-urethral reflux after Tur-TV in 20% of patients, when the tumour was localized in the trigonal area close to the urethral orifice. In 9 out of 96 patients bladder-ureteral reflux increased, in 4 patients bilateral reflux was noticed and in 5 patients reflux was due to the enlargement of the ureteral orifice. The patients followed a treatment with 9 endovesical instillations and only 2 patients underwent new resections because of local recurrence of the tumor. It is considered that chemical cystitis produced by repeated chemotherapeutic agents is the cause for the apparition of the bladder-ureteral reflux and its maintainance. The main cause for bladder-urethral reflux remains the alteration of the antireflux mechanism through the morphological and topographic alteration of the urethral orifice. The alteration of the antireflux mechanism was noticed in 43.3% of the patients with reflux and was not noticed in the patients without reflux.

In Gottfries and Nilssons study no severe stenosis was found at the follow-up investigation after the resection of the bladder tumor near the ureteric orifice. In all cases at least a 5 French catheter could be inserted.14

Amar and Das showed in most patients with reflux benign clinical findings, but it caused recurrent pyelonephritis in 9 cases and secondary struvite calculi in 2.10

The experience of See suggests that iatrogenic injury to the distal ureter during radical transurethral resection of tumor involving the hemi-trigone does not result in long-term distal ureteral damage.17

Some authors recommend catheterization of the ureteral orifice while resecting the bladder tumors close to the ureteral orifice.

In some cases the resection of the ureteral orifice should not be avoided.

Considering the low incidence of renal parenchimatose lesions due to reflux in only 6.7% of patients, we belief that a radical attitude is justified irrespective of the options some authors go for.18


References

1. Frang D, Zana J, Hubler J, Polyak L, Transurethral resection in bladder tumors, Acta Chir Acad Sci Hung. 1981;22(1-2):75-84.

2. Chepurov AK, Nemenova AA, The complications of transurethral resection of the bladder for tumor, Urol Nefrol (Mosk). 1996 Mar-Apr;(2):21-3.

3. Jorgensen TM, Dynamics of the urinary tract in longterm vesico-ureteric reflux in pigs. III, Scand J Urol Nephrol. 1985;19(3):183-91.

4. Aboulker P, Les lesions de luretre juxta-vesical dans la chirugie endiscopique de la vessie, Journal dUrologie. Seance du 23 fevrier, 1976, 879.

5. Amar AD, Das S, Vesicoureteric reflux in patients with bladder tumours, Br J Urol. 1983 Oct;55(5):483-7.

6. Nummi P, Ylonen N, Vesico-ureteral reflux following transurethral slitting of the ureteral orifice, Ann Chir Gynaecol Fenn. 1975;64(4):220-3.

7. Morita T, Tokue A, Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guerin against carcinoma in situ of the bladder, Urol Int. 2004;73(3):287-8.

8. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Huguet-Perez J, Vicente-Rodriguez J, Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J Urol. 2000 Oct;164(4):1183-7.

9. Gonzalez Martin M, Sousa Escandon A, Busto Castanon L, Gomez Veiga F, Chantada Abal V, Serrano Barrientos J, Endoscopic treatment of vesicoureteral reflux following transurethral resection of a vesical carcinoma by Teflon injection. Eur Urol. 1991;19(4):291-4.

10. Amar A, Das S, Vesicoureteric reflux in patient with bladder tumours, Br. J. Urol., 1983, 55:483.

11. Tanagho E, Huthc J, Mayers F, y Rambo O, Primary vesicoureteral reflux: Experimental studies of its etiology, J. Urol., 1965, 93:165.

12. Rafique M, Javed AA, Role of intravenous urography and transabdominal ultrasonography in the diagnosis of bladder carcinoma, Int Braz J Urol. 2004 May-Jun;30(3):185-90; discussion 191.

13. Lee SK, Chang Y, Park NH, Kim YH, Woo S, Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: comparative study with voiding cystourethrography, J Magn Reson Imaging. 2005 Apr;21(4):406-14.

14. Gotffries A, Nilsson s, Sundin T, Viklund, Late effects of transurethal resection of bladder tumours at the ureteric orifice, Scand. J. Urol. Nephrol., 1982, 9:32.

15. Mukamel E, Glany I, Nissenkorn I, Cytron S, Unancitipated vesicoureteral reflux: A possible sequela of long-term thio-tepa instillations to the bladder, J. Urol. 1985, 133:198.

16. Ricos Torrent, Casnova J, I. Iborra et al. Incidencia del reflujo vesico-ureteral tras la cirurgia endoscopica de los tumores vesicales superficiale. Estudio prospectivo. Arch. Esp. De Urol.1990, 43,2(136-140).

17. See WA, Distal ureteral regeneration after radical transurethral bladder tumor resection. Urology. 2000 Feb;55(2):212-5; discussion 215-6.

18. Amar A, Das S, Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated vesicoureteral reflux, J. Urol, 1985, 133:49.

 

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