- Email: [email protected]
Re: Clonal Origin of Multifocal Renal Cell Carcinoma as Determined by Microsatellite Analysis
0022-5347/03/1704-1325/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 170, 1325–1328, October 2003 Printed in U.S.A.
Letters to the Editor RE: EDITORIAL: THE LONG-TERM FOLLOWUP OF PRENATALLY DETECTED SEVERE BILATERAL NEWBORN HYDRONEPHROSIS INITIALLY MANAGED NONOPERATIVELY
2. Josephson, S.: Antenatally detected, unilateral dilatation of the renal pelvis: a critical review. 2. Postnatal non-operative treatment—long-term hazards, urgent research. Scand J Urol Nephrol, 36: 251, 2002 3. Piepsz, A., Hall, M., Ham, H. R., Verboven, M. and Collier, F.: Prospective management of neonates with pelviureteric junction stenosis. Therapeutic strategy based on 99m Tc-DPTA studies. Scand J Urol Nephrol, 23: 31, 1989 4. Josephson, S.: Antenatally detected, unilateral dilatation of the renal pelvis: a critical review. 1. Postnatal non-operative treatment 20 years on—is it safe? Scand J Urol Nephrol, 36: 243, 2002
Craig A. Peters J Urol, 168: 1121–1122, 2002 To the Editor. Onen et al report results with initially nonoperative treatment in bilateral hydronephrosis that are as good as those in unilateral cases.1 However, Peters raises several objections in the accompanying editorial (pp. 1121–1122). Onen et al state that an operation was performed “if urinary obstruction developed [emphasis added] . . ..” Peters claims, “All of these kidneys are obstructed to some extent” (which is impossible to prove— constitutional hydronephrosis certainly exists), and that “to separate obstructed from nonobstructed” is unrealistic (certainly, since the grade of obstruction varies continuously from mild to severe). Furthermore, pelvic dilatation can decrease despite persistent obstruction, and recurrence of dilatation depends on aggravation of the original obstruction. The authors’ later wording, “. . .[if] signs [emphasis added] of obstruction develop” is, thus, more correct. The theoretical comments by Peters are interesting but do not affect the message: increased dilatation may indicate progressing obstruction with imminent renal damage, and must be treated accordingly. Eleven cases of this sort were operated on, and the delay did not affect the results. Resolution allows watchful waiting—the 1 to 15-year results were indeed encouraging. Long-term followup goes without saying—in both therapy groups.2 The function assessment by the authors includes differential function without global estimate. Peters indicates this definite weakness, which is true of publications in this context, with one exception, and is especially serious in case of bilaterality.3 Peters suggests concentration ability and acid-base homeostasis as global parameters, which are excellent for focusing tubular state (sadly overlooked) but are dubious as a substitute for global moiety to differential function. Differential function alone is not informative in case of continued normality. A decrease is an alarm, and led Onen et al to operate on 5 kidneys. Maybe even this was overdoing it but what else can be done until we know better? Peters is worried about the difficulty in establishing a reliable function early. Onen et al did several timely investigations, which seems reassuring, and the delay did not seem harmful. The study also includes grade 3 hydronephrosis. Peters states that these cases have the widest variance (is this proved?) and considers them unfit for the study. However, Onen et al had only 8 cases of grade 4 initially, while the other 11 cases had progressed to grade 4 from initial grade 3. So, if stripped of grade 3, the article probably would not have been written. This would have been a shame—now we know a bit more about bilateral hydronephrosis. The nonoperative notion should not be discarded even in case of bilaterality. In the 1980s a negative attitude prevailed concerning unilateral cases—nevertheless, watchful waiting became adopted worldwide.4 Obviously, the protocol must be strict and obligatorily include a global function. The risks then seem small and the gain notable. This article concerns a subject not much explored, which was comprehensibly presented and was of great value for those who escaped operation—at the price of a number of renograms, maybe, but that is better than an operation. Alternatively, all patients would have been operated on— on both sides!
DOI: 10.1097/01.ju.0000085563.41515.3f
RE: CLONAL ORIGIN OF MULTIFOCAL RENAL CELL CARCINOMA AS DETERMINED BY MICROSATELLITE ANALYSIS K. Junker, K. Thrum, A. Schlichter, G. Mu¨ller, W. Hindermann and J. Schubert J Urol, 168: 2632–2636, 2002 To the Editor. The authors analyzed 6 microsatellite loci at chromosome 3p in 41 renal cell tumors obtained from 19 patients, and concluded that “the majority of multifocal clear cell renal carcinomas have a common clonal origin” and that “the clear cell satellite tumors are probably the result of metastases from the primary tumor rather than independent, new onset tumor growth.” The authors detected loss of heterozygosity (LOH) exclusively at the von Hippel-Lindau or the fragile histidine triad locus in 4 tumors each, and found a “zebra” pattern of loss of heterozygosity, eg multiple nonsyntenic deletions along chromosome 3p in 14 of the 41 tumors. They detected a size “shift” of DNA fragments amplified from tumor tissues in 38 of the 234 polymerase chain reactions. Such shift was seen in tumors of 10 of the 19 patients. These findings are remarkable, and are in strong disagreement with previous chromosomal and LOH studies. Although the authors did not mention it in the article, comprehensive cytogenetic analyses of sporadic and hereditary conventional renal cell carcinoma (RCC) show a deletion of the entire chromosome 3p14.2-pter region in more than 95% of the cases.1–3 These findings have also been confirmed by deletion mapping.4, 5 These data exclude the possibility of retaining the heterozygosity at any locus within the deleted 3p14.2-pter segment, eg the “zebra” pattern of LOH. During microsatellite analysis of more than 75 loci along chromosomes 3p, 6q, 8p, 9p and 14q in 105 conventional RCCs we did not find “shifting” of the amplified fragments.4 –11 Therefore, the data published by Junker et al suggest that conventional RCCs with tendency to metastatic growth within the same kidney have unique genetics. Alternatively, they used DNA from unmatched normal and tumor tissues in several cases showing shift.
Respectfully, Staffan Josephson Institution Women & Children’s Health Karolinska Institute Z6:04 Karolinska Hospital S-171 76 Stockholm, Sweden 1. Ulman, I., Jayanthi, V. R. and Koff, S. A.: The long-term followup of newborns with severe unilateral hydronephrosis initially managed nonoperatively. J Urol, 164: 1101, 2000 1325
Respectfully, Gyula Kovacs Department of Molecular Oncology Universitatsklinikum Heidelberg Im Neuenheimer Feld 325, Room 03 D-69120, Heidelberg, Germany 1. Kovacs, G. and Frisch, S.: Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res, 49: 651, 1989 2. Kovacs, G., Emanuel, A., Neumann, H. P. and Kung, H. F.: Cytogenetics of renal cell carcinomas associated with von Hippel-Lindau disease. Genes Chromosomes Cancer, 3: 256, 1991 3. Gunawan, B., Huber, W., Holtrup, M., von Heydebreck, A., Efferth, T., Poustka, A. et al: Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis. Cancer Res, 61: 7731, 2001
1326
LETTERS TO THE EDITOR
4. Chudek, J., Wilhelm, M., Bugert, P., Herbers, J. and Kovacs, G.: Detailed microsatellite analysis of chromosome 3p region in non-papillary renal cell carcinomas. Int J Cancer, 73: 225, 1997 5. Sukosd, F., Kuroda, N., Beothe, T., Kaur, A. P. and Kovacs, G.: Deletion of chromosome 3p14.2-p25 involving the VHL and FHIT genes in conventional renal cell carcinoma. Cancer Res, 63: 455, 2003 6. Bugert, P., Kenck, C., Wilhelm, M. and Kovacs, G.: Refining a proximal breakpoint cluster at chromosome 3p11.2 in nonpapillary renal cell carcinomas. Int J Cancer, 68: 723, 1996 7. Chudek, J., Wilhelm, M., Bugert, P., Herbers, J. and Kovacs, G.: Detailed microsatellite analysis of chromosome 3p region in non-papillary renal cell carcinomas. Int J Cancer, 73: 225, 1997 8. Herbers, J., Schullerus, D., Muller, H., Kenck, C., Chudek, J., Weimer, J. et al: Significance of chromosome 14q loss in nonpapillary renal cell carcinomas. Genes Chromosomes Cancer, 19: 29, 1997 9. Schullerus, D., Herbers, J., Chudek, J., Kanamaru, H. and Kovacs, G.: Loss of heterozygosity at chromosomes 8p, 9p and 14q is associated with stage and grade of non-papillary renal cell carcinomas. J Pathol, 183: 151, 1997 10. Schullerus, D., von Knobloch, R., Chudek, J., Herbers, J. and Kovacs, G.: Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma. Int J Cancer, 80: 22, 1999 11. Wilhelm, M., Bugert, P., Kenck, C., Staehler, G. and Kovacs, G.: Terminal deletion of chromosome 3p sequences in nonpapillary renal cell carcinomas: a breakpoint cluster between loci D3S1285 and D3S1603. Cancer Res, 55: 5383, 1995
Reply by Authors. The detected alterations of different regions on chromosome 3p are in agreement with other published data.1–3 These groups also found losses of heterozygosity on multiple loci in the same tumor sample. It was hypothesized that there are several alterations on 3p that are necessary for the development of malignant clear cell tumors. Whether the multifocal clear cell tumors represent a unique entity regarding their genetic pattern should be investigated in further studies. 1. van den Berg, A. and Buys, C. H.: Involvement of multiple loci on chromosome 3 in renal cell cancer development. Genes Chromosomes Cancer, 19: 59, 1997 2. Gronwald, J., Hadaczek, P., Storkel, S., Holtgreve-Grez, H., Rabbitts, P., Cremer, T. et al: Molecular evidence for derivation of metastatic cells from minor subclones of primary clear renal cell carcinomas. Cancer Detect Prev, 23: 479, 1999 3. Buentig, N., Storkel, S. and Atzpodien, J.: Molecular genetic changes in renal cell carcinomas. Urologe A, 41: 475, 2002 DOI: 10.1097/01.ju.0000086752.86595.a9
RE: SURGICAL TECHNIQUES FOR TREATING A RENAL NEOPLASM INVADING THE INFERIOR VENA CAVA A. Vaidya, G. Ciancio and M. Soloway J Urol, 169: 435– 444, 2003 To the Editor. The authors have written an extensive review of the surgical techniques including historical aspects for management of renal tumor extending into the inferior vena cava (IVC). The surgical concept has hardly changed in the last decade. However, the important advancement in the management has been increasing accuracy of magnetic resonance imaging (MRI). This test not only determines the level of intracaval tumor, but also gives more information about the nature and likely invasion of the wall of the IVC by the tumor.1 The role of MRI has received little attention in this review. Although the review is intended to cover surgical techniques, the role of MRI deserves mentioning. The MRI is likely to give more information that is useful for planning the extraction of the caval tumor. It also differentiates pure thrombus from the tumor. In this respect the use of the phrase “thrombus” or “caval thrombus” is loose and mislead-
ing. The caval contents could be pure thrombus, thrombus and tumor, or tumor itself. Respectfully, Vinod H. Nargund St. Bartholomew’s Hospital, and Queen Mary School of Medicine and Dentistry West Smithfield, London EC1A 7BE United Kingdom 1. Sohaib, S. A. A., Teo, J., Nargund, V. H., Lumley, J. S. P., Hendry, W. F. and Reznek, R. H.: Assessment of tumor invasion of the vena caval wall in renal cell carcinoma cases by magnetic resonance imaging. J Urol, 167: 1271, 2002
Reply by Authors. We appreciate the insightful comments by Nargund. We agree that MRI is reasonably accurate in determining the level of intracaval thrombus, and may provide information about the content of the thrombus and whether there is invasion of the wall of the IVC.1 We routinely obtain an MRI in the preoperative evaluation of these patients. We agree that there can be a nontumor containing thrombus associated with a tumor thrombus in a chronically obstructed vena cava, and, thus, we do not specifically need an MRI to give us this information. The more important point is that regardless of whether the thrombus contains tumor, it needs to be completely excised. 1. Goldfarb, D. A., Novick, A. C., Lorig, R., Bretan, P. N., Montie, J. E., Pontes, J. E. et al: Magnetic resonance imaging for assessment of vena caval tumor thrombi: a comparative study with venacavography and computerized tomography scanning. J Urol, 144: 1100, 1990 DOI: 10.1097/01.ju.0000085583.60525.38
RE: AN INTERVAL LONGER THAN 12 WEEKS BETWEEN THE DIAGNOSIS OF MUSCLE INVASION AND CYSTECTOMY IS ASSOCIATED WITH WORSE OUTCOME IN BLADDER CARCINOMA R. F. Sa´ nchez-Ortiz, W. C. Huang, R. Mick, K. N. van Arsdalen, A. J. Wein and S. B. Malkowicz J Urol, 169: 110 –115, 2003 To the Editor. This article evaluated outcomes for patients who underwent cystectomy at different time points after the diagnosis of muscle invasive cancer. The authors concluded that 12 weeks was the cutoff point at which a delay in cystectomy was associated with a worse outcome. They suggested that surgery scheduling could be flexible within this 12-week time frame to accommodate patient needs such as seeking second opinions. The authors established the 12-week cutoff point by combining “similar” hazard ratios from the univariate survival analysis presented in table 4 in the article. The weeks to cystectomy hazard ratios of 1.00, 0.88, 1.30 and 0.70 for delays of less than 4 weeks, 4 to 6 weeks, 7 to 9 weeks and 10 to 12 weeks, respectively, were deemed similar, and hazard ratios of 1.76 and 3.89 for delays of 13 to 16 weeks and greater than 16 weeks, respectively, were deemed similar. Using these definitions of similarity, only 19 patients (10%) had a delay in cystectomy of greater than 12 weeks. However, one could argue that hazard ratios of 1.00 and 0.88 are similar, and hazard ratios of 1.30, 0.70, 1.76 and 3.89 are similar. This would create a cutoff of 6 weeks or less versus a greater than 6-week delay in cystectomy. With this cutoff point 109 patients (58%) would have a delay of greater than 6 weeks to cystectomy. To examine the potential impact of a 6-week cutoff point we evaluated the data in table 3 in the article by Fisher’s exact test. We found a statistically significant difference in the percentages of organ confined disease at the 6-week cutoff point (61% organ confined at up to 6 weeks, 39% organ confined at greater than 6 weeks, p ⫽ 0.003). We also found a statistically significant difference in the percentages of negative nodes at the 6-week cutoff (76% negative nodes at up to 6 weeks, 61% negative nodes at greater than 6 weeks, p ⫽ 0.029). We were unable to perform more definitive univariate and multivariate survival analyses using the 6-week cutoff because the necessary information required for these methods was not provided in the
Vol. 170, 1325–1328, October 2003 Printed in U.S.A.
Letters to the Editor RE: EDITORIAL: THE LONG-TERM FOLLOWUP OF PRENATALLY DETECTED SEVERE BILATERAL NEWBORN HYDRONEPHROSIS INITIALLY MANAGED NONOPERATIVELY
2. Josephson, S.: Antenatally detected, unilateral dilatation of the renal pelvis: a critical review. 2. Postnatal non-operative treatment—long-term hazards, urgent research. Scand J Urol Nephrol, 36: 251, 2002 3. Piepsz, A., Hall, M., Ham, H. R., Verboven, M. and Collier, F.: Prospective management of neonates with pelviureteric junction stenosis. Therapeutic strategy based on 99m Tc-DPTA studies. Scand J Urol Nephrol, 23: 31, 1989 4. Josephson, S.: Antenatally detected, unilateral dilatation of the renal pelvis: a critical review. 1. Postnatal non-operative treatment 20 years on—is it safe? Scand J Urol Nephrol, 36: 243, 2002
Craig A. Peters J Urol, 168: 1121–1122, 2002 To the Editor. Onen et al report results with initially nonoperative treatment in bilateral hydronephrosis that are as good as those in unilateral cases.1 However, Peters raises several objections in the accompanying editorial (pp. 1121–1122). Onen et al state that an operation was performed “if urinary obstruction developed [emphasis added] . . ..” Peters claims, “All of these kidneys are obstructed to some extent” (which is impossible to prove— constitutional hydronephrosis certainly exists), and that “to separate obstructed from nonobstructed” is unrealistic (certainly, since the grade of obstruction varies continuously from mild to severe). Furthermore, pelvic dilatation can decrease despite persistent obstruction, and recurrence of dilatation depends on aggravation of the original obstruction. The authors’ later wording, “. . .[if] signs [emphasis added] of obstruction develop” is, thus, more correct. The theoretical comments by Peters are interesting but do not affect the message: increased dilatation may indicate progressing obstruction with imminent renal damage, and must be treated accordingly. Eleven cases of this sort were operated on, and the delay did not affect the results. Resolution allows watchful waiting—the 1 to 15-year results were indeed encouraging. Long-term followup goes without saying—in both therapy groups.2 The function assessment by the authors includes differential function without global estimate. Peters indicates this definite weakness, which is true of publications in this context, with one exception, and is especially serious in case of bilaterality.3 Peters suggests concentration ability and acid-base homeostasis as global parameters, which are excellent for focusing tubular state (sadly overlooked) but are dubious as a substitute for global moiety to differential function. Differential function alone is not informative in case of continued normality. A decrease is an alarm, and led Onen et al to operate on 5 kidneys. Maybe even this was overdoing it but what else can be done until we know better? Peters is worried about the difficulty in establishing a reliable function early. Onen et al did several timely investigations, which seems reassuring, and the delay did not seem harmful. The study also includes grade 3 hydronephrosis. Peters states that these cases have the widest variance (is this proved?) and considers them unfit for the study. However, Onen et al had only 8 cases of grade 4 initially, while the other 11 cases had progressed to grade 4 from initial grade 3. So, if stripped of grade 3, the article probably would not have been written. This would have been a shame—now we know a bit more about bilateral hydronephrosis. The nonoperative notion should not be discarded even in case of bilaterality. In the 1980s a negative attitude prevailed concerning unilateral cases—nevertheless, watchful waiting became adopted worldwide.4 Obviously, the protocol must be strict and obligatorily include a global function. The risks then seem small and the gain notable. This article concerns a subject not much explored, which was comprehensibly presented and was of great value for those who escaped operation—at the price of a number of renograms, maybe, but that is better than an operation. Alternatively, all patients would have been operated on— on both sides!
DOI: 10.1097/01.ju.0000085563.41515.3f
RE: CLONAL ORIGIN OF MULTIFOCAL RENAL CELL CARCINOMA AS DETERMINED BY MICROSATELLITE ANALYSIS K. Junker, K. Thrum, A. Schlichter, G. Mu¨ller, W. Hindermann and J. Schubert J Urol, 168: 2632–2636, 2002 To the Editor. The authors analyzed 6 microsatellite loci at chromosome 3p in 41 renal cell tumors obtained from 19 patients, and concluded that “the majority of multifocal clear cell renal carcinomas have a common clonal origin” and that “the clear cell satellite tumors are probably the result of metastases from the primary tumor rather than independent, new onset tumor growth.” The authors detected loss of heterozygosity (LOH) exclusively at the von Hippel-Lindau or the fragile histidine triad locus in 4 tumors each, and found a “zebra” pattern of loss of heterozygosity, eg multiple nonsyntenic deletions along chromosome 3p in 14 of the 41 tumors. They detected a size “shift” of DNA fragments amplified from tumor tissues in 38 of the 234 polymerase chain reactions. Such shift was seen in tumors of 10 of the 19 patients. These findings are remarkable, and are in strong disagreement with previous chromosomal and LOH studies. Although the authors did not mention it in the article, comprehensive cytogenetic analyses of sporadic and hereditary conventional renal cell carcinoma (RCC) show a deletion of the entire chromosome 3p14.2-pter region in more than 95% of the cases.1–3 These findings have also been confirmed by deletion mapping.4, 5 These data exclude the possibility of retaining the heterozygosity at any locus within the deleted 3p14.2-pter segment, eg the “zebra” pattern of LOH. During microsatellite analysis of more than 75 loci along chromosomes 3p, 6q, 8p, 9p and 14q in 105 conventional RCCs we did not find “shifting” of the amplified fragments.4 –11 Therefore, the data published by Junker et al suggest that conventional RCCs with tendency to metastatic growth within the same kidney have unique genetics. Alternatively, they used DNA from unmatched normal and tumor tissues in several cases showing shift.
Respectfully, Staffan Josephson Institution Women & Children’s Health Karolinska Institute Z6:04 Karolinska Hospital S-171 76 Stockholm, Sweden 1. Ulman, I., Jayanthi, V. R. and Koff, S. A.: The long-term followup of newborns with severe unilateral hydronephrosis initially managed nonoperatively. J Urol, 164: 1101, 2000 1325
Respectfully, Gyula Kovacs Department of Molecular Oncology Universitatsklinikum Heidelberg Im Neuenheimer Feld 325, Room 03 D-69120, Heidelberg, Germany 1. Kovacs, G. and Frisch, S.: Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res, 49: 651, 1989 2. Kovacs, G., Emanuel, A., Neumann, H. P. and Kung, H. F.: Cytogenetics of renal cell carcinomas associated with von Hippel-Lindau disease. Genes Chromosomes Cancer, 3: 256, 1991 3. Gunawan, B., Huber, W., Holtrup, M., von Heydebreck, A., Efferth, T., Poustka, A. et al: Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis. Cancer Res, 61: 7731, 2001
1326
LETTERS TO THE EDITOR
4. Chudek, J., Wilhelm, M., Bugert, P., Herbers, J. and Kovacs, G.: Detailed microsatellite analysis of chromosome 3p region in non-papillary renal cell carcinomas. Int J Cancer, 73: 225, 1997 5. Sukosd, F., Kuroda, N., Beothe, T., Kaur, A. P. and Kovacs, G.: Deletion of chromosome 3p14.2-p25 involving the VHL and FHIT genes in conventional renal cell carcinoma. Cancer Res, 63: 455, 2003 6. Bugert, P., Kenck, C., Wilhelm, M. and Kovacs, G.: Refining a proximal breakpoint cluster at chromosome 3p11.2 in nonpapillary renal cell carcinomas. Int J Cancer, 68: 723, 1996 7. Chudek, J., Wilhelm, M., Bugert, P., Herbers, J. and Kovacs, G.: Detailed microsatellite analysis of chromosome 3p region in non-papillary renal cell carcinomas. Int J Cancer, 73: 225, 1997 8. Herbers, J., Schullerus, D., Muller, H., Kenck, C., Chudek, J., Weimer, J. et al: Significance of chromosome 14q loss in nonpapillary renal cell carcinomas. Genes Chromosomes Cancer, 19: 29, 1997 9. Schullerus, D., Herbers, J., Chudek, J., Kanamaru, H. and Kovacs, G.: Loss of heterozygosity at chromosomes 8p, 9p and 14q is associated with stage and grade of non-papillary renal cell carcinomas. J Pathol, 183: 151, 1997 10. Schullerus, D., von Knobloch, R., Chudek, J., Herbers, J. and Kovacs, G.: Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma. Int J Cancer, 80: 22, 1999 11. Wilhelm, M., Bugert, P., Kenck, C., Staehler, G. and Kovacs, G.: Terminal deletion of chromosome 3p sequences in nonpapillary renal cell carcinomas: a breakpoint cluster between loci D3S1285 and D3S1603. Cancer Res, 55: 5383, 1995
Reply by Authors. The detected alterations of different regions on chromosome 3p are in agreement with other published data.1–3 These groups also found losses of heterozygosity on multiple loci in the same tumor sample. It was hypothesized that there are several alterations on 3p that are necessary for the development of malignant clear cell tumors. Whether the multifocal clear cell tumors represent a unique entity regarding their genetic pattern should be investigated in further studies. 1. van den Berg, A. and Buys, C. H.: Involvement of multiple loci on chromosome 3 in renal cell cancer development. Genes Chromosomes Cancer, 19: 59, 1997 2. Gronwald, J., Hadaczek, P., Storkel, S., Holtgreve-Grez, H., Rabbitts, P., Cremer, T. et al: Molecular evidence for derivation of metastatic cells from minor subclones of primary clear renal cell carcinomas. Cancer Detect Prev, 23: 479, 1999 3. Buentig, N., Storkel, S. and Atzpodien, J.: Molecular genetic changes in renal cell carcinomas. Urologe A, 41: 475, 2002 DOI: 10.1097/01.ju.0000086752.86595.a9
RE: SURGICAL TECHNIQUES FOR TREATING A RENAL NEOPLASM INVADING THE INFERIOR VENA CAVA A. Vaidya, G. Ciancio and M. Soloway J Urol, 169: 435– 444, 2003 To the Editor. The authors have written an extensive review of the surgical techniques including historical aspects for management of renal tumor extending into the inferior vena cava (IVC). The surgical concept has hardly changed in the last decade. However, the important advancement in the management has been increasing accuracy of magnetic resonance imaging (MRI). This test not only determines the level of intracaval tumor, but also gives more information about the nature and likely invasion of the wall of the IVC by the tumor.1 The role of MRI has received little attention in this review. Although the review is intended to cover surgical techniques, the role of MRI deserves mentioning. The MRI is likely to give more information that is useful for planning the extraction of the caval tumor. It also differentiates pure thrombus from the tumor. In this respect the use of the phrase “thrombus” or “caval thrombus” is loose and mislead-
ing. The caval contents could be pure thrombus, thrombus and tumor, or tumor itself. Respectfully, Vinod H. Nargund St. Bartholomew’s Hospital, and Queen Mary School of Medicine and Dentistry West Smithfield, London EC1A 7BE United Kingdom 1. Sohaib, S. A. A., Teo, J., Nargund, V. H., Lumley, J. S. P., Hendry, W. F. and Reznek, R. H.: Assessment of tumor invasion of the vena caval wall in renal cell carcinoma cases by magnetic resonance imaging. J Urol, 167: 1271, 2002
Reply by Authors. We appreciate the insightful comments by Nargund. We agree that MRI is reasonably accurate in determining the level of intracaval thrombus, and may provide information about the content of the thrombus and whether there is invasion of the wall of the IVC.1 We routinely obtain an MRI in the preoperative evaluation of these patients. We agree that there can be a nontumor containing thrombus associated with a tumor thrombus in a chronically obstructed vena cava, and, thus, we do not specifically need an MRI to give us this information. The more important point is that regardless of whether the thrombus contains tumor, it needs to be completely excised. 1. Goldfarb, D. A., Novick, A. C., Lorig, R., Bretan, P. N., Montie, J. E., Pontes, J. E. et al: Magnetic resonance imaging for assessment of vena caval tumor thrombi: a comparative study with venacavography and computerized tomography scanning. J Urol, 144: 1100, 1990 DOI: 10.1097/01.ju.0000085583.60525.38
RE: AN INTERVAL LONGER THAN 12 WEEKS BETWEEN THE DIAGNOSIS OF MUSCLE INVASION AND CYSTECTOMY IS ASSOCIATED WITH WORSE OUTCOME IN BLADDER CARCINOMA R. F. Sa´ nchez-Ortiz, W. C. Huang, R. Mick, K. N. van Arsdalen, A. J. Wein and S. B. Malkowicz J Urol, 169: 110 –115, 2003 To the Editor. This article evaluated outcomes for patients who underwent cystectomy at different time points after the diagnosis of muscle invasive cancer. The authors concluded that 12 weeks was the cutoff point at which a delay in cystectomy was associated with a worse outcome. They suggested that surgery scheduling could be flexible within this 12-week time frame to accommodate patient needs such as seeking second opinions. The authors established the 12-week cutoff point by combining “similar” hazard ratios from the univariate survival analysis presented in table 4 in the article. The weeks to cystectomy hazard ratios of 1.00, 0.88, 1.30 and 0.70 for delays of less than 4 weeks, 4 to 6 weeks, 7 to 9 weeks and 10 to 12 weeks, respectively, were deemed similar, and hazard ratios of 1.76 and 3.89 for delays of 13 to 16 weeks and greater than 16 weeks, respectively, were deemed similar. Using these definitions of similarity, only 19 patients (10%) had a delay in cystectomy of greater than 12 weeks. However, one could argue that hazard ratios of 1.00 and 0.88 are similar, and hazard ratios of 1.30, 0.70, 1.76 and 3.89 are similar. This would create a cutoff of 6 weeks or less versus a greater than 6-week delay in cystectomy. With this cutoff point 109 patients (58%) would have a delay of greater than 6 weeks to cystectomy. To examine the potential impact of a 6-week cutoff point we evaluated the data in table 3 in the article by Fisher’s exact test. We found a statistically significant difference in the percentages of organ confined disease at the 6-week cutoff point (61% organ confined at up to 6 weeks, 39% organ confined at greater than 6 weeks, p ⫽ 0.003). We also found a statistically significant difference in the percentages of negative nodes at the 6-week cutoff (76% negative nodes at up to 6 weeks, 61% negative nodes at greater than 6 weeks, p ⫽ 0.029). We were unable to perform more definitive univariate and multivariate survival analyses using the 6-week cutoff because the necessary information required for these methods was not provided in the