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Hemorrhagic complications after nephron-sparing surgery: Angiographic diagnosis and management by transcatheter embolization
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R. Flanigan / Urologic Oncology: Seminars and Original Investigations 24 (2006) 81– 88
examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. Results: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56 – 6.09; P ⬍ 0.001) for clear cell, 4.20 (CI: 1.65–10.68; P ⬍ 0.001) for chromophobe, and 1.49 (CI: 0.81–2.74; P ⫽ 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P ⬍ 0.001). Conclusions: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.
Commentary It has been suggested for some time that necrosis within renal cell carcinoma (RCC) is a poor prognostic feature. In this series of 2445 patients with RCC that displayed tumor necrosis (including 28% clear cell cancers, 47% papillary cancers, and 20% chromophobe RCC), the authors found a highly significant correlation between necrosis and death from cancer, yielding a risk ratio of 5.27 for patients with clear cell cancer, 1.49 for papillary cancer, and 4.20 for chromophobe cancer. Importantly, this study identified tumor necrosis as an independent prognostic factor, even when TNM stage, tumor size, and nuclear grade were adjusted for in a multivariate analysis. doi:10.1016/j.urolonc.2005.11.010 Robert Flanigan, M.D. pT1 substaging in renal cell carcinoma: Validation of the 2002 TNM staging modification of malignant renal epithelial tumors. Salama ME, Guru K, Stricker H, Peterson E, Peabody J, Menon M, Amin MB, De Peralta-Venturina M, Department of Pathology, Henry Ford Hospital, Detroit, MI. J Urol 2005;173:1492–5 Purpose: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. Materials and Methods: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. Results: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p ⫽ 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p ⫽ 0.001). All statistical analyses were adjusted for age and sex. Conclusions: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.
Commentary It is well known to practicing urologists that the staging system for localized renal cell carcinoma has varied widely over the years. Most recently, in the 2002 TNM system, T1 tumors were classified as tumors up to 7.0 cm in diameter. Furthermore, T1 tumors were subdivided into T1a (ⱕ4 cm) and T1b (⬎4.0 and up to 7.0 cm). In this series of 259 nephrectomies, 115 were T1a and 95 were T1b. The authors confirm the validity of the subdivision of T1 tumors. This is important information because it may also direct the manner in which we follow these patients after nephrectomy in a manner based on their tumor stage. doi:10.1016/j.urolonc.2005.11.011 Robert Flanigan, M.D. Hemorrhagic complications after nephron-sparing surgery: Angiographic diagnosis and management by transcatheter embolization. Heye S, Maleux G, Van Poppel H, Oyen R, Wilms G, Department of Radiology, University Hospitals Gasthuisberg, Belgium. AJR Am J Roentgenol 2005;184:1661– 4 Objective: Nephron-sparing surgery has become an accepted treatment technique for renal cell carcinoma in properly selected patients. Although rare, major postoperative hemorrhage can occur and is usually accompanied by gross hematuria with or without acute flank pain
R. Flanigan / Urologic Oncology: Seminars and Original Investigations 24 (2006) 81– 88
83
at the site of prior surgery. In this retrospective study, the immediate radiologic and clinical success and the long-term follow-up of transcatheter embolization are evaluated. Conclusion: Transcatheter selective embolization is a safe and effective technique for appropriate management of this postoperative vascular complication.
Commentary In this article, the authors report on their experience with an uncommon but dangerous complication of nephron-sparing surgery: significant hemorrhage. This study makes several important points: (1) significant hemorrhage occurs in 0% to 5% of these patients (2.8% in this study); (2) hemorrhage occurs at a mean interval of 8.9 days; (3) hemorrhage presented in 2 distinct ways (i.e., significant hematuria or flank pain with a significant decrease in hemoglobin); and (4) transarterial embolization was therapeutic in all cases reported in this series. The urologist performing nephron-sparing surgery should be familiar with the clinical presentation and treatment of significant hemorrhage, and should warn patients that this complication may occur after surgery. doi:10.1016/j.urolonc.2005.11.006 Robert Flanigan, M.D. Management of isolated renal fossa recurrence following radical nephrectomy. Master VA, Gottschalk AR, Kane C, Carroll PR, Department of Urology, Department of Radiation Oncology, University of California, San Francisco, CA. J Urol 2005;174:473–7 Purpose: Local recurrence of renal cell carcinoma in the renal fossa without distant metastatic disease is an infrequent occurrence. Management of this lesion can be challenging, with relatively few series in the literature. We describe our use of surgical extirpation with adjuvant intraoperative radiation. Materials and Methods: The University of California, San Francisco Urologic Oncology database and the University of California, San Francisco Radiation Oncology database were queried for all patients with locally recurrent renal fossa recurrence. Only patients with recurrence of renal cell carcinoma in the renal fossa were included. Survival, complications and the use of adjuvant therapy in the form of intraoperative radiation therapy were noted. Results: A total of 14 patients were treated for this lesion between 1990 and 2003. Mean time to recurrence was 40 months (range 5 to 180). Only 1 patient was symptomatic preoperatively, while in 13 disease had been detected on routine computerized tomography followup. Mean size of the recurrent tumor was 6.35 cm (range 2 to 17). 9 patients died of progressive, metastatic disease after a mean of 17 months (range 1 to 56) and 5 are alive with a mean survival of 66 months (range 14 to 86). The time to recurrence after nephrectomy approached statistical significance (p ⫽ 0.06) when comparing the patients who were alive vs those who died of disease. Additionally, there was no statistical difference in size of mass recurrence between these 2 groups. There was no difference in survival due to adjuvant intraoperative radiation therapy. Local fossa re-recurrence developed in 2 patients. Survival was 40% at 2 years and 30% at 5 years from surgery. Complications, including minor complications, occurred in 42% of patients and there was no perioperative mortality. Conclusions: Selected patients with isolated local recurrence in the renal fossa may have favorable and durable outcomes following surgical resection and possibly adjuvant intraoperative radiation therapy for isolated renal fossa recurrence following radical nephrectomy. Development of novel and effective systemic therapy is needed in high risk patients with renal cancer.
Commentary Isolated renal fossa recurrence is an unusual event, occurring in 1% to 2% of most nephrectomy series. This article makes several important observations, including: (1) most of these recurrences are asymptomatic and detected only on abdominal imaging; (2) the length of time from nephrectomy to observed fossa recurrence is a predictor of patient survival (a longer interval is better); and (3) complications occur in a large minority of these resections, with pancreatic fistula being the most common one described in this series. The urologist should perform an extensive evaluation for distant metastases in this patient population before proceeding to surgery. doi:10.1016/j.urolonc.2005.11.007 Robert Flanigan, M.D. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). Aass N, De Mulder PHM, Mickisch GHJ, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ, Department of Clinical Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. J Clin Oncol 2005;23:4172– 8 Purpose: A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.
R. Flanigan / Urologic Oncology: Seminars and Original Investigations 24 (2006) 81– 88
examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. Results: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56 – 6.09; P ⬍ 0.001) for clear cell, 4.20 (CI: 1.65–10.68; P ⬍ 0.001) for chromophobe, and 1.49 (CI: 0.81–2.74; P ⫽ 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P ⬍ 0.001). Conclusions: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.
Commentary It has been suggested for some time that necrosis within renal cell carcinoma (RCC) is a poor prognostic feature. In this series of 2445 patients with RCC that displayed tumor necrosis (including 28% clear cell cancers, 47% papillary cancers, and 20% chromophobe RCC), the authors found a highly significant correlation between necrosis and death from cancer, yielding a risk ratio of 5.27 for patients with clear cell cancer, 1.49 for papillary cancer, and 4.20 for chromophobe cancer. Importantly, this study identified tumor necrosis as an independent prognostic factor, even when TNM stage, tumor size, and nuclear grade were adjusted for in a multivariate analysis. doi:10.1016/j.urolonc.2005.11.010 Robert Flanigan, M.D. pT1 substaging in renal cell carcinoma: Validation of the 2002 TNM staging modification of malignant renal epithelial tumors. Salama ME, Guru K, Stricker H, Peterson E, Peabody J, Menon M, Amin MB, De Peralta-Venturina M, Department of Pathology, Henry Ford Hospital, Detroit, MI. J Urol 2005;173:1492–5 Purpose: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. Materials and Methods: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. Results: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p ⫽ 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p ⫽ 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p ⫽ 0.001 and 5.49, p ⫽ 0.001) and for the CRCC subtype (RR 5.50, p ⫽ 0.001 and 5.18, p ⫽ 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p ⫽ 0.001). All statistical analyses were adjusted for age and sex. Conclusions: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.
Commentary It is well known to practicing urologists that the staging system for localized renal cell carcinoma has varied widely over the years. Most recently, in the 2002 TNM system, T1 tumors were classified as tumors up to 7.0 cm in diameter. Furthermore, T1 tumors were subdivided into T1a (ⱕ4 cm) and T1b (⬎4.0 and up to 7.0 cm). In this series of 259 nephrectomies, 115 were T1a and 95 were T1b. The authors confirm the validity of the subdivision of T1 tumors. This is important information because it may also direct the manner in which we follow these patients after nephrectomy in a manner based on their tumor stage. doi:10.1016/j.urolonc.2005.11.011 Robert Flanigan, M.D. Hemorrhagic complications after nephron-sparing surgery: Angiographic diagnosis and management by transcatheter embolization. Heye S, Maleux G, Van Poppel H, Oyen R, Wilms G, Department of Radiology, University Hospitals Gasthuisberg, Belgium. AJR Am J Roentgenol 2005;184:1661– 4 Objective: Nephron-sparing surgery has become an accepted treatment technique for renal cell carcinoma in properly selected patients. Although rare, major postoperative hemorrhage can occur and is usually accompanied by gross hematuria with or without acute flank pain
R. Flanigan / Urologic Oncology: Seminars and Original Investigations 24 (2006) 81– 88
83
at the site of prior surgery. In this retrospective study, the immediate radiologic and clinical success and the long-term follow-up of transcatheter embolization are evaluated. Conclusion: Transcatheter selective embolization is a safe and effective technique for appropriate management of this postoperative vascular complication.
Commentary In this article, the authors report on their experience with an uncommon but dangerous complication of nephron-sparing surgery: significant hemorrhage. This study makes several important points: (1) significant hemorrhage occurs in 0% to 5% of these patients (2.8% in this study); (2) hemorrhage occurs at a mean interval of 8.9 days; (3) hemorrhage presented in 2 distinct ways (i.e., significant hematuria or flank pain with a significant decrease in hemoglobin); and (4) transarterial embolization was therapeutic in all cases reported in this series. The urologist performing nephron-sparing surgery should be familiar with the clinical presentation and treatment of significant hemorrhage, and should warn patients that this complication may occur after surgery. doi:10.1016/j.urolonc.2005.11.006 Robert Flanigan, M.D. Management of isolated renal fossa recurrence following radical nephrectomy. Master VA, Gottschalk AR, Kane C, Carroll PR, Department of Urology, Department of Radiation Oncology, University of California, San Francisco, CA. J Urol 2005;174:473–7 Purpose: Local recurrence of renal cell carcinoma in the renal fossa without distant metastatic disease is an infrequent occurrence. Management of this lesion can be challenging, with relatively few series in the literature. We describe our use of surgical extirpation with adjuvant intraoperative radiation. Materials and Methods: The University of California, San Francisco Urologic Oncology database and the University of California, San Francisco Radiation Oncology database were queried for all patients with locally recurrent renal fossa recurrence. Only patients with recurrence of renal cell carcinoma in the renal fossa were included. Survival, complications and the use of adjuvant therapy in the form of intraoperative radiation therapy were noted. Results: A total of 14 patients were treated for this lesion between 1990 and 2003. Mean time to recurrence was 40 months (range 5 to 180). Only 1 patient was symptomatic preoperatively, while in 13 disease had been detected on routine computerized tomography followup. Mean size of the recurrent tumor was 6.35 cm (range 2 to 17). 9 patients died of progressive, metastatic disease after a mean of 17 months (range 1 to 56) and 5 are alive with a mean survival of 66 months (range 14 to 86). The time to recurrence after nephrectomy approached statistical significance (p ⫽ 0.06) when comparing the patients who were alive vs those who died of disease. Additionally, there was no statistical difference in size of mass recurrence between these 2 groups. There was no difference in survival due to adjuvant intraoperative radiation therapy. Local fossa re-recurrence developed in 2 patients. Survival was 40% at 2 years and 30% at 5 years from surgery. Complications, including minor complications, occurred in 42% of patients and there was no perioperative mortality. Conclusions: Selected patients with isolated local recurrence in the renal fossa may have favorable and durable outcomes following surgical resection and possibly adjuvant intraoperative radiation therapy for isolated renal fossa recurrence following radical nephrectomy. Development of novel and effective systemic therapy is needed in high risk patients with renal cancer.
Commentary Isolated renal fossa recurrence is an unusual event, occurring in 1% to 2% of most nephrectomy series. This article makes several important observations, including: (1) most of these recurrences are asymptomatic and detected only on abdominal imaging; (2) the length of time from nephrectomy to observed fossa recurrence is a predictor of patient survival (a longer interval is better); and (3) complications occur in a large minority of these resections, with pancreatic fistula being the most common one described in this series. The urologist should perform an extensive evaluation for distant metastases in this patient population before proceeding to surgery. doi:10.1016/j.urolonc.2005.11.007 Robert Flanigan, M.D. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). Aass N, De Mulder PHM, Mickisch GHJ, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ, Department of Clinical Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. J Clin Oncol 2005;23:4172– 8 Purpose: A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.