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ABO(H) isoantigens and urine
anatomic location of the lesion, plus its papillary configuration, possibly could account for the apparent low incidence of its occurrence. Careful cystoscopic evaluation of the floor of the prostatic urethra might yield more of these lesions in the future. Ahmed C. Baroudy, M.D. Joseph P. O’Connell, M.D. Armed Forces Hospital King Abdulaziz Airbase Dhahran, Saudi Arabia
ABO(H) ISOANTIGENS
AND URINE
To the Editor: In an article on “Correlation of ABH Antigenicity and Urine Cytology Results in Transitional Cell Carcinoma of Bladder,” published in September issue (vol. 24, pages 287-290, 1984) of UROLOGY Gorelick and associates have attempted to compare urothelial ABO(H) isoantigen expression with urinary cytology. Their hypothesis asserted that these properties reflect increased cellular dedifferentiation and should be related. Results obtained did not support a correlation between loss of ABO(H) antigens and increased sensitivity of urinary cytology or increased tumor grade. Advanced histologic grade in transitional cell carcinoma of the urinary bladder is a well-known risk factor for progession to invasive disease1.2 and correlates with a progressive loss of ABO(H) isoantigens.l-g Although 63 per cent of low-grade (I,II), superficial bladder carcinomas are positive for ABO(H) isoantigens, while only 23 per cent of highgrade (III), superficial tumors are positive, isoantigen expression is not merely a reflection of histologic grade,9 and in fact represents an independent prognostic indicator in patients with noninvasive bladder tumors. Several studie+‘O have confirmed the usefulness of detecting ABO(H) isoantigen deletion by predicting subsequent muscle invasion in 84 per cent of patients with superficial bladder tumors. Detection of isoantigens also predicts that only 6 per cent of highgrade superficial bladder tumors, which maintain their ABO(H) isoantigens, will develop invasive tumor.Q Although 90 per cent of isoantigen negative tumors recur, 46 per cent of isoantigen positive tumors also recur, and therefore, detection of ABO(H) isoantigens is of limited value in predicting tumor recurrence.8 Exfoliative cytologic studies including urinary cytology and bladder washings with periodic cystoscopic examinations are the primary means of detection of early recurrence.“,‘2 The sensitivity of exfoliative studies increases with histologic grade,
336
and the sensitivity of bladder-washing specimens is consistently superior to conventional urinary cytology 11.12Exfoliative cytologic studies may determine the presence of malignant cells and their histologic grade. Although increased sensitivity of cytologic studies is indirectly related to invasive tumors, exfoliative studies cannot determine the presence of tumor invasion.r2,13 Therefore, ABO(H) isoantigen deletion is correlated with histologic grade but independent of it, and similarly, sensitivity of urinary cytology is correlated with tumor invasion but independent of it. Furthermore, two of the articles that the author cites, in order to detract from the usefulness of ABO(H) isoantigen testing, are not applicable. A study by Kay and Wallace14 was performed in 1961 using a mixed cell agglutination reaction on cell suspensions (not tissue sections) of tumor scrapings, and probably reflected error associated with normal urothelium present in cell suspensions. In another study, Askari and associatesi reported no greater predictability of prognosis from antigenicity than grade alone. Half of their patients, however, were blood group 0, and 91 per cent of them were isoantigen negative by specific red cell adherence (SRCA) test. The significance of these data was subsequently challenged without response from the authors.le The SRCA test has proved to be consistently ineffective in detecting the H antigen associated with blood type 0 (34% false negative rate in normal urothelium),17 and many investigators have attempted to improve these results by using frozen tissue sections,rs (to maximize tissue antigenic reactivity), Bombay blood5,1g (with a high titer of anti-H antibody), or the lectin immunoperoxidase technique used by Gorelick and associates. William R. Strand, M.D. Robert G. McAlpine, M.D. U.S. Naval Hospital Bethesda, Maryland 20014 References 1. Lange PH, Limas C, and Fraley EE: Tissue blood group antigens and prognosis in low-stage transitional cell carcinoma of the bladder, J Urol 119: 52 (1978). 2. Limas C, Lange PH, Fraley EE, and Vessella RL: A,B,H, antigens in transitional cell tumors of the urinary bladder, Cancer 44: 2099 (1979). 3. Decenzo JM, Howard P, and Irish CE: Antigenic deletion and prognosis of patients with stage A transitional cell bladder carcinoma, J Urol 114: 874 (1975). 4. Bergman S, and Javadpour N: The cell surface antigen A,B or O(H) as an indicator for malignant potential in stage A bladder carcinoma, ibid 119: 49 (1978). 5. Emmott RC. Iavadnour N, Bergman SM. and Soares T: Correlation of the cell s&face antigens with stage and grade on cancer of the bladder. ibid 121: 37 (1979). 6. Richie JP, Blute’RD, and Waisman J: Immunologic indicators of prognosis in bladder cancer. The importance of the cell surface antigens, ibid 123: 22 (1980).
UROLOGY
/ MARCH 1985
/ VOLUME XXV, NUMBER 3
7. Johnson JD, and Lamm DL: Prediction of bladder tumor invasion with the mixed cell agglutination test, ibid 123: 25 (1980). 8. Newman AJ Jr, Carlton CE Jr, and Johnson S: Cell surface A, B or O(H) blood group antigens as an indicator of malignant potential in stage A bladder carcinoma, ibid 124: 27 (1980). 9. Catalona WJ: Practical utility of specific red cell adherence test in bladder cancer, Urology 18: 113 (1981). 10. Lange PH, and Limas C: Tissue blood group antigen testing in transitional cell carcinoma of the bladder (Letter to Ed), J U&l 124: 304 (1980). 11. Rife CC. Farrow GM. and Utz DC: Urine cytology of transitional cell’neoplasms, Urol Clin North Am 6: 599 (19%). 12. Zein T, et al: Evaluation of bladder washings and urine cytology in diagnosis of bladder cancer and its correlation with selected biopsies of bladder mucosa, J Urol 132: 670 (1984). 13. Morrison DA, Murphy WM, Ford KS, and Soloway MS: Surveillance of Stage 0, Grade I bladder cancer by cytology alone, is it acceptable, ibid 132: 672 (1984). 14. Kay HF, and Wallace DM: A and B antigens of tumor arising from urinary epithelium, J Nat1 Cancer Inst 26: 1349 (1961). 15. Askari A, Colemanares E, Saberi A, and Jarman WD: Red cell surface antigen and its relationship to survival of patients with transitional cell carcinoma of the bladder. _ I Urol 125: 182 (1981). 16. Javadpour N: Role of ABH isoantigen in bladder cancer (Letter to Ed), ibid 127: 341 (1982). 17. Coon JS, and Weinstein‘RS: Variability in the expression of the O(H) antigen in human transitional epithelium, ibid 125: 301 (1981). 18. Limas C, and Lange PH: Altered reactivity for A,B, H antigens in transitional cell carcinomas of the urinary bladder. A study of the mechanisms involved, Cancer 46: 1366 (1980). 19. Srinivas C, and Kiruluta HG: ABO(H) isoantigens in bladder tumors: A new technique of quantitative analysis, J Urol 131: 245 (1984).
REPLY OF DR. GORELICK To the Editor: Though the primary objective of our study was to determine the relationship between ABO(H) antigenicity and diagnostic accuracy of urine cytology in patients with transitional cell carcinoma of the bladder, we also were able to review and examine the prognostic role of ABO(H) antigens. Our intent was not to dismiss the value of the latter, but instead to point out some of the outstanding problems and obstacles preventing it from becoming an independent, reliable prognostic tool. Deficiencies of the specific red cell adherence (SRCA) test include: lack of objective quantification, variations in fixation methods possibly altering antigenicity, and considerable false negative rates in blood group O(H) patients. Since the publication of our article, further work has appeared addressing these issues. Srinivas and Kiruluta’ used a single tumor cell separation technique for quantitative analysis of ABO(H) antigen as opposed to the more common use of tissue sections. They also used Bombay blood anti-H antisera for blood group O(H) patients. They showed a mean of 88 per cent of cells from biopsies of normal bladder
UROLOGY
i
MARCH 1985
/ VOLUME XXV, NUMBER 3
ABH(0) positive specimens compared to a statistically significant lower fraction of cells (range of O77%) from various grades of bladder tumors. This study also revealed an impressive accuracy for determining antigen status in patients with type O(H) blood. In a more recent work from the same institution, Srinivas et al2 showed the antigen status distribution of those patients with type O(H) blood to be equal to those of other blood groups, negating the previously problematic occurrence of false negative results in this group. They also quantified ABO(H) results and correlated this with tumor grade and stage. These recent advancements can only increase the accuracy and value of ABO(H) antigen studies in transitional cell carcinoma. However, the question of whether ABO(H) status will be applicable in the clinical setting of therapeutic decision-making, whether alone or in combination with other indicators of tumor behavior, still needs to be answered. Jeffrey Gorelick, M.D. The New York Hospital Cornell Medical Center New York, New York 10021 References 1. Srinivas V, and Kiruluta HG: ABO(H) isoantigens in bladder tumors: a new technique of quantitative analysis, J Urol 131: 245 (1984). 2. Srinivas V, et al: Estimation of ABO(H) isoantigen expression in bladder tumors, ibid 133: 25 (1985).
REDUCTION
OF PARAPHIMOSIS
To the Editor: I am writing in response to the article, “Simple Method of Reduction of Paraphimosis,” by S. U. Ganti, N. Sayegh, and J. C. Addonizio published in the January issue (vol. 25, page 77, 1985), of UROLOGY. There are numerous tricks in so many areas of urology, and this condition certainly tests our ingenuity. Most urologists feel that any of the techniques would be much more humane and enthusiastically accepted by the patient if we took a few moments to inject some lidocaine hydrochloride (Xylocaine) aseptically and block the dorsal nerve of the penis. Furthermore, with that anesthesia an unsuccessful reduction could be quickly followed by an emergency dorsal slit.
Veterans
Dennis J. Krauss, M.D. Associate Professor of Urology Administration Medical Center 800 Irving Avenue Syracuse, New York 13210
337
ABO(H) ISOANTIGENS
AND URINE
To the Editor: In an article on “Correlation of ABH Antigenicity and Urine Cytology Results in Transitional Cell Carcinoma of Bladder,” published in September issue (vol. 24, pages 287-290, 1984) of UROLOGY Gorelick and associates have attempted to compare urothelial ABO(H) isoantigen expression with urinary cytology. Their hypothesis asserted that these properties reflect increased cellular dedifferentiation and should be related. Results obtained did not support a correlation between loss of ABO(H) antigens and increased sensitivity of urinary cytology or increased tumor grade. Advanced histologic grade in transitional cell carcinoma of the urinary bladder is a well-known risk factor for progession to invasive disease1.2 and correlates with a progressive loss of ABO(H) isoantigens.l-g Although 63 per cent of low-grade (I,II), superficial bladder carcinomas are positive for ABO(H) isoantigens, while only 23 per cent of highgrade (III), superficial tumors are positive, isoantigen expression is not merely a reflection of histologic grade,9 and in fact represents an independent prognostic indicator in patients with noninvasive bladder tumors. Several studie+‘O have confirmed the usefulness of detecting ABO(H) isoantigen deletion by predicting subsequent muscle invasion in 84 per cent of patients with superficial bladder tumors. Detection of isoantigens also predicts that only 6 per cent of highgrade superficial bladder tumors, which maintain their ABO(H) isoantigens, will develop invasive tumor.Q Although 90 per cent of isoantigen negative tumors recur, 46 per cent of isoantigen positive tumors also recur, and therefore, detection of ABO(H) isoantigens is of limited value in predicting tumor recurrence.8 Exfoliative cytologic studies including urinary cytology and bladder washings with periodic cystoscopic examinations are the primary means of detection of early recurrence.“,‘2 The sensitivity of exfoliative studies increases with histologic grade,
336
and the sensitivity of bladder-washing specimens is consistently superior to conventional urinary cytology 11.12Exfoliative cytologic studies may determine the presence of malignant cells and their histologic grade. Although increased sensitivity of cytologic studies is indirectly related to invasive tumors, exfoliative studies cannot determine the presence of tumor invasion.r2,13 Therefore, ABO(H) isoantigen deletion is correlated with histologic grade but independent of it, and similarly, sensitivity of urinary cytology is correlated with tumor invasion but independent of it. Furthermore, two of the articles that the author cites, in order to detract from the usefulness of ABO(H) isoantigen testing, are not applicable. A study by Kay and Wallace14 was performed in 1961 using a mixed cell agglutination reaction on cell suspensions (not tissue sections) of tumor scrapings, and probably reflected error associated with normal urothelium present in cell suspensions. In another study, Askari and associatesi reported no greater predictability of prognosis from antigenicity than grade alone. Half of their patients, however, were blood group 0, and 91 per cent of them were isoantigen negative by specific red cell adherence (SRCA) test. The significance of these data was subsequently challenged without response from the authors.le The SRCA test has proved to be consistently ineffective in detecting the H antigen associated with blood type 0 (34% false negative rate in normal urothelium),17 and many investigators have attempted to improve these results by using frozen tissue sections,rs (to maximize tissue antigenic reactivity), Bombay blood5,1g (with a high titer of anti-H antibody), or the lectin immunoperoxidase technique used by Gorelick and associates. William R. Strand, M.D. Robert G. McAlpine, M.D. U.S. Naval Hospital Bethesda, Maryland 20014 References 1. Lange PH, Limas C, and Fraley EE: Tissue blood group antigens and prognosis in low-stage transitional cell carcinoma of the bladder, J Urol 119: 52 (1978). 2. Limas C, Lange PH, Fraley EE, and Vessella RL: A,B,H, antigens in transitional cell tumors of the urinary bladder, Cancer 44: 2099 (1979). 3. Decenzo JM, Howard P, and Irish CE: Antigenic deletion and prognosis of patients with stage A transitional cell bladder carcinoma, J Urol 114: 874 (1975). 4. Bergman S, and Javadpour N: The cell surface antigen A,B or O(H) as an indicator for malignant potential in stage A bladder carcinoma, ibid 119: 49 (1978). 5. Emmott RC. Iavadnour N, Bergman SM. and Soares T: Correlation of the cell s&face antigens with stage and grade on cancer of the bladder. ibid 121: 37 (1979). 6. Richie JP, Blute’RD, and Waisman J: Immunologic indicators of prognosis in bladder cancer. The importance of the cell surface antigens, ibid 123: 22 (1980).
UROLOGY
/ MARCH 1985
/ VOLUME XXV, NUMBER 3
7. Johnson JD, and Lamm DL: Prediction of bladder tumor invasion with the mixed cell agglutination test, ibid 123: 25 (1980). 8. Newman AJ Jr, Carlton CE Jr, and Johnson S: Cell surface A, B or O(H) blood group antigens as an indicator of malignant potential in stage A bladder carcinoma, ibid 124: 27 (1980). 9. Catalona WJ: Practical utility of specific red cell adherence test in bladder cancer, Urology 18: 113 (1981). 10. Lange PH, and Limas C: Tissue blood group antigen testing in transitional cell carcinoma of the bladder (Letter to Ed), J U&l 124: 304 (1980). 11. Rife CC. Farrow GM. and Utz DC: Urine cytology of transitional cell’neoplasms, Urol Clin North Am 6: 599 (19%). 12. Zein T, et al: Evaluation of bladder washings and urine cytology in diagnosis of bladder cancer and its correlation with selected biopsies of bladder mucosa, J Urol 132: 670 (1984). 13. Morrison DA, Murphy WM, Ford KS, and Soloway MS: Surveillance of Stage 0, Grade I bladder cancer by cytology alone, is it acceptable, ibid 132: 672 (1984). 14. Kay HF, and Wallace DM: A and B antigens of tumor arising from urinary epithelium, J Nat1 Cancer Inst 26: 1349 (1961). 15. Askari A, Colemanares E, Saberi A, and Jarman WD: Red cell surface antigen and its relationship to survival of patients with transitional cell carcinoma of the bladder. _ I Urol 125: 182 (1981). 16. Javadpour N: Role of ABH isoantigen in bladder cancer (Letter to Ed), ibid 127: 341 (1982). 17. Coon JS, and Weinstein‘RS: Variability in the expression of the O(H) antigen in human transitional epithelium, ibid 125: 301 (1981). 18. Limas C, and Lange PH: Altered reactivity for A,B, H antigens in transitional cell carcinomas of the urinary bladder. A study of the mechanisms involved, Cancer 46: 1366 (1980). 19. Srinivas C, and Kiruluta HG: ABO(H) isoantigens in bladder tumors: A new technique of quantitative analysis, J Urol 131: 245 (1984).
REPLY OF DR. GORELICK To the Editor: Though the primary objective of our study was to determine the relationship between ABO(H) antigenicity and diagnostic accuracy of urine cytology in patients with transitional cell carcinoma of the bladder, we also were able to review and examine the prognostic role of ABO(H) antigens. Our intent was not to dismiss the value of the latter, but instead to point out some of the outstanding problems and obstacles preventing it from becoming an independent, reliable prognostic tool. Deficiencies of the specific red cell adherence (SRCA) test include: lack of objective quantification, variations in fixation methods possibly altering antigenicity, and considerable false negative rates in blood group O(H) patients. Since the publication of our article, further work has appeared addressing these issues. Srinivas and Kiruluta’ used a single tumor cell separation technique for quantitative analysis of ABO(H) antigen as opposed to the more common use of tissue sections. They also used Bombay blood anti-H antisera for blood group O(H) patients. They showed a mean of 88 per cent of cells from biopsies of normal bladder
UROLOGY
i
MARCH 1985
/ VOLUME XXV, NUMBER 3
ABH(0) positive specimens compared to a statistically significant lower fraction of cells (range of O77%) from various grades of bladder tumors. This study also revealed an impressive accuracy for determining antigen status in patients with type O(H) blood. In a more recent work from the same institution, Srinivas et al2 showed the antigen status distribution of those patients with type O(H) blood to be equal to those of other blood groups, negating the previously problematic occurrence of false negative results in this group. They also quantified ABO(H) results and correlated this with tumor grade and stage. These recent advancements can only increase the accuracy and value of ABO(H) antigen studies in transitional cell carcinoma. However, the question of whether ABO(H) status will be applicable in the clinical setting of therapeutic decision-making, whether alone or in combination with other indicators of tumor behavior, still needs to be answered. Jeffrey Gorelick, M.D. The New York Hospital Cornell Medical Center New York, New York 10021 References 1. Srinivas V, and Kiruluta HG: ABO(H) isoantigens in bladder tumors: a new technique of quantitative analysis, J Urol 131: 245 (1984). 2. Srinivas V, et al: Estimation of ABO(H) isoantigen expression in bladder tumors, ibid 133: 25 (1985).
REDUCTION
OF PARAPHIMOSIS
To the Editor: I am writing in response to the article, “Simple Method of Reduction of Paraphimosis,” by S. U. Ganti, N. Sayegh, and J. C. Addonizio published in the January issue (vol. 25, page 77, 1985), of UROLOGY. There are numerous tricks in so many areas of urology, and this condition certainly tests our ingenuity. Most urologists feel that any of the techniques would be much more humane and enthusiastically accepted by the patient if we took a few moments to inject some lidocaine hydrochloride (Xylocaine) aseptically and block the dorsal nerve of the penis. Furthermore, with that anesthesia an unsuccessful reduction could be quickly followed by an emergency dorsal slit.
Veterans
Dennis J. Krauss, M.D. Associate Professor of Urology Administration Medical Center 800 Irving Avenue Syracuse, New York 13210
337