International Urology and Nephrology 24 (5), pp. 503--508 (1992)

Transurethral Ultrasonography, Fiberoptic Cystoscopy and Bladder Washout Cytology in the Evaluation of Bladder Tumours A. AKDA~, L. Tf2RKERI, D. ERSEV, A. ERSEV,* S. KULLU* Departments of Urology and *Pathology, Marmara University School of Medicine, Istanbul, Turkey (Accepted January 10, 1992) The impact of transurethral ultrasonography, fiberoptic cystoscopy and bladder washout cytology on assessment of bladder tumours was investigated in this study. Transurethral ultrasonography had an accuracy rate of 96.5 % in diagnosing and staging bladder tumours. The accuracy rates of fiberoptic cystoscopy and washout cytology were 90.9 % and 73.7 %, respectively, in diagnosis. The efficacy of transurethral ultrasonography was found to be high enough for routine employment in the evaluation of the bladder tumours. Fiberoptic cystoscopy in conjunction with washout cytology as a combination relatively easy to perform can be used especially for follow-up purposes of the bladder tumours.

Introduction The detection, staging and follow-up of bladder cancer should be considered as a whole. Various clinical methods were applied in order to obtain reliable results in this setting. Cystoscopy is the most accurate technique in diagnosing the tumours. Transurethral ultrasonography (TU US) owing to its potential advantages has become a useful tool both in diagnosis and staging of bladder tumours with an accuracy rate o f 95% [1, 2]. The traditionally applied procedure for follow-up of patients with bladder tumours includes cystoscopy and random biopsies. Fiberoptic cystoscopy is a relatively less invasive technique than conventional rigid cystoscopy and can be used under local anaesthesia. As the importance of urinary cytology in evaluating the entire urothelium has been understood, a new method was introduced in the late 1960s for cytologic detection in bladder irrigation specimens [3]. Urinary cytology together with fiberoptic cystoscopy can provide a less invasive and reliable combination, especially for the follow-up of bladder tumours. This study was undertaken to evaluate the accuracy o f T U US, fiberoptic cystoscopy and cytologic examination in the evaluation of bladder tumours.

VSP, Utrecht Akad~miai Kiad6, Budapest

504

A k d a s et aL : Diagnostics o f bladder tumour

Materials and methods

A total of 104 patients who underwent cystoscopy with or without further endoscopic intervention for suspected or follow-up bladder tumours were investigated. Diagnosis was made by histopathological examination of surgical specimens and the patients were staged according to the TNM system (1982 classification). Briefly, clinical examination, excretory urography, abdominopelvic CT scanning, chest X-ray, cystoscopy, bimanual examination under anaesthesia and biopsy or transurethral resection of the tumour(s) with random biopsies were the procedures performed in diagnosis and staging. The cystoscopic findings were noted as negative, or positive for malignancy. TU US was performed in all patients, while cytologic specimens were collected from 91 patients and fiberoptic cystoscopy was performed in 52 cases. In the follow-up procedure of the bladder tumours biopsy of the visible lesion(s) and/or suspected areas and four random biopsies were done during every cystoscopic examination. Staging by TU US was done in correlation with the T category as previously reported by Schiiller et al. [4] and the accuracy rates were compared with those of other diagnostic methods as previously described. In 11 patients who underwent radical cystectomy the results of histopathologic examination made it possible to obtain the definitive accuracy rate of TU US. Fiberoptic cystoscopy was performed by 18 French Wolf fiberoptic cystoscope under local anaesthesia, followed by rigid cystocopy with general anaesthesia in all patients. Bladder barbotage was done with 50 ml of saline through the sheath of the endoscope after it was introduced into the bladder. The irrigation specimen was immediately fixed in an equal amount of 96 % alcohol, centrifuged at 2500 rpm for 20 minutes, the supernatant was decanted and the pellet smeared onto three slides and stained by the Papanicolaou technique [5]. Histopathologic classification was done according to the World Health Organization system. For the purpose of this study cytological preparations were classified as either negative (including normal, reactive and hyperplastic cells) or positive for neoplasia, which were further divided into low grade (grades I and II) and high grade neoplasms (grade III and CIS) as previously described [6]. Results

Bladder tumours were detected in 76 of the 104 patients (73.1 ~o). Eighteen patients who had received radiotherapy with curative intent were excluded from the study because of irradiation sequelae (oedema, fibrosis, etc.) with satisfactory TU US interpretation. In the remaining 86 patients there were two false negative results and one false positive. Among the 58 cases with proved bladder tumours 56 were accurately diagnosed and staged. Thus, the overall accuracy rate of TU US in diagnosing and staging of bladder carcinoma in our eligible patient group was 96.5 ~ (Table 1). International Urology and Nephrolofly 24, 1992

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Akdas et al.." Diaynostics o f bladder tumour

A total of 11 patients underwent radical surgery during this study. Pathological examination of the cystectomy specimens revealed down-staging in 2 cases due to neo-adjuvant chemotherapy. Excluding these cases T U US was found to be accurate in staging of 88.9 % o f the remaining 9 cases (8/9 patients), in 2 cases there were T2 tumours, while 4 of them were T3 and 2 were T4. In one case, TI tumour within a diverticulum was overstaged as T4 due to intense echogenicity caused by calcifications within the tumour. Two male patients (3.8 %) could not tolerate the fiberoptic cystoscopy. There were 26 visible lesions detected by rigid cystoscopy in this particular group of patients. Biopsies from these lesions revealed transitional cell carcinoma in 21, chronic cystitis in three and atypical hyperplasia due to radiation therapy in two. Table 1 Diagnosis of bladder tumours with TU US Accurate diagnosis

No. o f patients

Bladder tumour (+) Bladder tumour (--) Total

No.

Per cent

58 28

56 27

96.5 96.4

86

83

96.5

Staging of bladder tumours with TU US No. o f

Accurate staging

patients

Ta-T1 (U1) T2 (U2) T3 (U3) T4 (U4) Total

No.

26 7 12 11

25 7 11 11

56

54

P e r cent

96.2 100.0

91.7 100.0

Table 2 Accuracy rates of flexible and rigid cystoscopy is diagnosis of bladder carcinoma No. of patients

Accurate diagnosis No.

Per cent

Flexible cystoscopy (Patients with TCC)

22

20

90.9

Rigid cystoscopy (Patients with TCC)

22

21

95.5

TCC: Transitional cell carcinoma International Urology and Nephrology 24, 1992

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Akdar et aL : Diagnostics o f bladder tumour

Tabe 3 Accuracy o f cytology in diagnosis of bladder cancer

Missed diagnosis due to improper fixation/staining by cytology Accurate diagnosis by cytology Total number of patients

No.

Per cent

4 28 38

10.5 23.7

Table 4 Correlation of histologic and cytologic grading of turnouts in cytologically evaluable cases Patients

Low-grade tumours (Grades I-II) High-grade tumours (Grade III-CIS) Total

Accuracy by cytology

No.

Per cent

No.

Per cent

18

52.9

13/18

72.2

16

47.1

15/16

93.8

34

100.0

28/34

82.4

In one patient carcinoma in situ (CIS) in random biopsy could not be detected either by fiberoptic or rigid cystoscopy. An overall accuracy rate of 90.9 % (20/22) and 95.5 % (21/22) was reached by fiberoptic and rigid cystoscopy, respectively (Table 2). Out of 91 cytologic specimens, 10 (11%) were inadequate for evaluation due to improper fixation and/or staining. Thirty-eight of 91 cases were diagnosed as transitional cell carcinoma at the end of the histopathological studies. In 4 of these cases cytologic material was inadequate for evaluation. Out of 38 turnouts diagnosed by histopathologic evaluation, 28 (sensitivity 73.7%) were diagnosed properly by washout cytology. There were 16 high-grade (grade III or CIS) and 18 low-grade (grades I and II) neoplasms. The accuracy rate of cytology was 93.8 and 72.2% in high- and low-grade neoplasms, respectively (Tables 3 and 4). Discussion

Since accurate staging of bladder carcinoma is of prime importance in both planning the optimum therapeutic approaches and for prognosis, various clinical methods were applied in order to obtain reliable results. Yet no single method has proved to be sufficient for this purpose [1 ]. International Urology and Nephrology 24, 1992

Akdar et aL : Diagnostics o f bladder tumour

507

The rationale for intracorporeal ultrasonography is to achieve better resolution of body structures of interest by a much closer approach, and by avoiding the interference of other bodily structures as much as possible. Watanabe and his associates have done major contribution to this field by their investigations on transrectal ultrasonography [7]. The first transurethral ultrasound scanner was developed in 1974 and found to be a superior technique in diagnosing and delineating the extent of bladder tumours [8]. Since then it has gained popularity for its high accuracy rates [1, 2]. The results of our study demonstrate that TU US is especially effective in discrimination between superficial and muscle invasive tumours, or locally advanced disease. This aspect dearly has a great impact on the choice of treatment. The major drawback of transurethral ultrasonography is its inability to distinguish irradiation sequelae (oedema, fibrosis, etc.) from residual tumour or recurrence, so that it cannot be used in staging the tumours in irradiated bladders [9]. Fiberoptic cystoscopy is a relatively less invasive technique because it is performed under local anaesthesia, introducing the device into the bladder as in a simple urethral catheterization and its calibre being less than a conventional rigid cystoscope. Fiberoptic cystoscope has also a working channel to obtain cold punch biopsies especially in control cystoscopies of bladder tumours. As our study implies, the accuracy rate of diagnosis with flexible cystoscopy is quite comparable to rigid conventional type (90.9~o and 95.5~, respectively). A high proportion of high-grade tumours and all CIS lesions have been diagnosed by cytologic examination of bladder irrigation specimens (Tables 3 and 4), in accordance with other investigators [10]. In the current literature the overall sensitivity of cytology is somewhere between 61 and 85~, with an average of 7 8 ~ (80 to 95~o for high-grade and 69.7 to 75 ~ for low-grade neoplasms, respectively) [6, 11, 12, 13, 14]. It has also been proposed that repeat cytologies may increase the sensitivity, approaching 100K on a theoretical basis [15]. Additionally, evaluation of the whole urothelium is possible by cytology and turnours smaller than 5 ram, CIS and non-exophytic tumours are most likely not detected by imaging studies but cytology [16]. This is the most important advantage of cytology, because CIS cannot always be diagnosed by conventional methods. On the other hand, the identification rate of low-grade tumors was significantly low. This aspect still remains to be a major drawback of the method. The technique must be applied properly in both fixation and staining to avoid inadequate specimens. In our study improper handling of the cytologic specimens precluded the diagnosis of bladder carcinoma in 10.5 ~o of the cases. The rate of accuracy of cytology from various trials as well as our study points out that it may be used as a conjunctive method in the follow-up of bladder tumours because of the importance of evaluating the whole urothelium. It may also be further simplified as voiding cytology. As a conclusion, TU US with very high accuracy rates in both diagnosis and staging, especially by delineating the extent of invasion, may prove very useful 4

International Urology and Nephrology 24, 1992

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in all cases with suspicion o f b l a d d e r carcinoma. D u r i n g the follow-up o f bladder t u m o u r s , fiberoptic cystoscopy a n d cytology seem to be reasonable alternatives for more invasive methods.

References 1. Nakamura, S., NiOima, T. : Staging of bladder cancer by ultrasonography: A new technique by transurethral intravesical scanning. 3". UroL, 124, 341 (1986). 2. Newhouse, J. H., Grant, D. C.: Transitional cell carcinoma. Radiology, Diagnosis, Imaging, Intervention. J. P. Lippincon Co., Philadelphia 1987. 3. Harris, M. J., Schwinn, C. P., Morrow, J. W. : Exfoliative cytology of the bladder irrigation specimen. Acta CytoL, 15, 385 (1971). 4. SchiJller, J., Walther, V., Schmiedt, E. : Intravesical ultrasound tomography in staging bladder carcinoma. J. UroL, 128, 264 (1982). 5. Papanicolaou, G. N., Marshall, V. F. : Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science, 101, 519 (1945). 6. Murphy, W. M., Soloway, M. S., Jukkola, A. F. : Urinary cytology and bladder cancer: The cellular features of transitional cell neoplasms. Cancer, 53, 1555 (1984). 7. Watanabe, H., Kato, H., Kato, T. : Diagnostic application of the ultrasonography to the prostate. Jap. J. Urol., 59, 273 (1968). 8. Holm, H. H., Northeved, A. : A transurethral ultrasonic scanner. J. Urol., 11, 238 (1974). 9. Holm, H. H., Juul, N., Torp-Pedersen. S.: Bladder tumor staging by transurethral ultrasonic scanning. Ettr. UroL, 15, 31 (1988). 10. Koss, L. G., Deitch, D., Ramanathan, R., Sherman, A. B. : Diagnostic value of cytology of voided urine. Acta CytoL, 29, 810 (1985). 11. Murphy, W. M., Emerson, L. D., Chandler, W. : Flow cytometry versus urinary cytology in the evaluation of patients with bladder cancer, at. UroL, 136, 815 (1986). 12. Badalament, R. A., Hermansen, D. K., Kimmel, M. : The sensitivity of bladder wash cytometry, bladder wash cytology, and voided cytology in the detection of bladder carcinoma. Cancer, 60, 1423 (1987). 13. Loening, S., Narayana, A., Yoder, L. : Longitudinal study of bladder cancer with cytology and biopsy. Br. J. UroL, 50, 496 (1978). 14. Dean, P. J., Murphy, W. M. : Importance of urinary cytology and future role of flow cytometry. Urology (Suppl. 26), 4, 11 (1985). 15. Badalement, R. A., Kimmel, M., Gay, H. : The sensitivity of flow cytometry compared with conventional cytology in the detection of superficial bladder carcinoma. Cancer, 59, 2078 (1987). 16. Juul, N., Torp-Pedersen, S., Larsen, S.: Bladder tumor control by abdominal ultrasound and urine cytology. Scand. J. UroL NeplwoL, 20, 275 (1986).

International Urology and Nephrolaqy 2,t, 1992

Transurethral ultrasonography, fiberoptic cystoscopy and bladder washout cytology in the evaluation of bladder tumours.

The impact of transurethral ultrasonography, fiberoptic cystoscopy and bladder washout cytology on assessment of bladder tumours was investigated in t...
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