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S127 LOCAL RECURRENCE IN THE RENAL FOSSA AFTER NEPHRECTOMY FOR RCC
S124
Evaluation of bcl-2 and P-53 markers as prognostic factors in patients with Clear Cell type renal cell carcinoma in patient undergone radical nephrectomy
Shahrokh H., Ajami H., Erfanian Daneshvar S. Hashemi Nejad, Dept. of Urology, Tehran, Iran Introduction & Objectives: To improve our understanding of the clinical relevance of p53, and bcl-2 proteins overexpression in clear cell type renal cell carcinoma ( ccRCC ), we retrospectively in a cohort group of patients investigated the immunohistochemical expression of p53, and bcl-2 and the relationship of this expression to clinicopathologic and prognostic characteristics. Material & Methods: The expression of p53 and bcl-2 was evaluated in 50 paraffin-embedded ccRCC specimens who has undergone radical nephrectomy in last 4 years in our center using immunohistochemistry.The clinical significance of these markers in relation to disease-specific survival and occurrence of metastasis or recurrence were analyzed. Patients followed up for 18 months (between 3 to 60 month).Variable factors including age, sex, tumor grade and stage, metastasis, recurrence and survival were analysed statistically in relation to the markers. Results: The expression of the p53 and bcl-2 protein was recognized in 12(25.5%) and 15(32.0%) cases, respectively; No correlation was noted between these two proteins and any clinicopathologic parameters, except bcl-2 expression and occurrence of metastasis.The detection level of p53 expression was consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl2 expression showed a correlation with probability of metastasis but could not be significantly correlated with other parameters and could not demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. Conclusions: Only bcl-2 attained independent prognostic significance in metastatic ccRCC. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC. Adjunctive use of bcl-2 and P-53staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC.At the present time, the combination of both tumor grade and stage represents the best prognostic markers available.
S125
Soluble CD30 as a predictor of acute renal allograft rejection
Kamali K. Hashemi Nejad Hospital, Dept. of Urology and Kidney Transplantation, Tehran, Iran Introduction & Objectives: Recent studies suggest that high pre and post renal transplant soluble CD30 levels may be associated with increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of serum sCD30 for prediction of acute graft rejection. Material & Methods: In this prospective study, we analyzed clinical data of 40 patients, whose pre and post transplant serum levels of sCD30 were detected by ELISA. Eight patients (20%) developed acute rejection (AR),12 patients showed delayed graft function (DGF) and 20 recipients experienced uncomplicated course group (UC) respectively. The patients were followed for 3 months and there was no death. Results: Preoperative sCD30 levels of three groups were 96.2±32.5, 80.2±28.3 and 76.8±29.8 U/ml, respectively (p=0.28).After transplantation significant decrease of sCD30 was detected in three groups on day 14 post-transplantation respectively (81.6±30.4, 63.2±28.5 and 55.5±27.7 U/ml respectively, p<0.001), while sCD30 levels of AR group remained significantly higher than DGF and non-rejecting patients(24.3±5.2,18.1±3.2 and 19.8±4.7 ng/ml respectively, p=0.02).Positive Panel reactive antibody(PRA)was not statistically different among groups(p=no significant).Also hemodialysis did not affect sCD30 levels(p=no significant). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 14 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 15 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Conclusions: Measurement of soluble CD30 on day 14 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.
S126
Chemotherapy with gemcitabine and 5 fluorouracil in patients with poor prognosis metastatic renal cell cancer – significant palliative role?
Janjic A., Bojanic N., Micic S., Vuksanovic A., Tulic C., Pejcic T. Urology Clinic Belgrade, Dept. of Urology, Belgrade, Serbia Introduction & Objectives: Determination of clinical resposnse rate of the
combination chemotherapy with weekly intravenous gemcitabine with 5 fluouracil ( 5FU) in patients with poor prognosis metastatic renal cell cancer ( RCC). Quality of life assessment prior and after cjemotherapy. Material & Methods: Between february 2007 and january 2010, 14 patients with metastatic RCC were enrolled onto this therapeutic protocol consisted of gemcitabine 1000mg/m2on days 1,8,15 and 5 FU 300mg/m2 on days 1 to 5 of a 28 days cicle. Patients had an ECOG performanse status of 0 to 3, with a median time since diagnosis of metastatic desease of 10 months. 10 patients ( 71.4%) had multiple metastatc sites and 4 patients had ( 28.5%) had massive locally advanced desease. Nephrectomy was performed in 12 patients and renal tumor biopsy in 2 . In all patients clear cell histology of RCC was defined with Fuhrman grades of 2 to 4. Minimal number of therapeutic cycles was 2, maximal 5 . Results: Of the all assessable patients, there were no complete resposnes, but 2 partial resposnes ( 14.2%) were detected. In 3 patients ( 21.4%) minor resposnes ( 25 to 50 % reduction in tumor size ) were observed.9 patients progressed ( 64.5%). The duration of resposnse in those 5 partial responses was 2,3,7, 8 and 14 months. The regimen was well tolerated, with fatigue,mucositis, nausea, vomiting, and grade 2 haematologic toxicities being the most common.Quality of life assessment was done with FACT G qustionnaire prior to chemotherapy and after completition of minimum 2 cycles of therapy, with average 43 points prior and 33 points after chemotherapy. Use of pain medication was less common during therapy. Conclusions: Weekly gemcitabine with 5 fluouracil is an active combination in patients with metastatic RCC.Therapy is wel ltolerated and produced an modest improvement in progression free survival with significant quality oflife benefits.
S127
Local recurrence in the renal fossa after nephrectomy for RCC
Yanev K., Ormanov D., Georgiev M., Dimitrov P., Vassilev V., Mladenov V., Simeonov P., Kirilov S., Timev A., Panchev P. Medical University Sofia, Dept. of Urology, Sofia, Bulgaria Introduction & Objectives: In the literature the frequency of local recurrence (LR) after radical nephrectomy for RCC varies between 0.77 to 4%. Based on our experience we created staging system of LR, based on TNM staging system and is in correlation with the Response Evaluation Criteria in Solid Tumors (RECIST-1). Material & Methods: For the period of 17 years (1992-2009) we had 1408 neprectomies for RCC. Of them 57 patients developed local recurrence. We implicated in practice two concepts – Degree of Aggressiveness of Local Recurrence (DALR) – which reflects the degree of invasion of the local recurrence in the adjacent tissues and Stage of DALR. Results: The cumulative incidence of LR in our study is 4.05%, but the real incidence drops to 1.77%, for those patients who had surgery in our department only. Of all cases of LR we operated 37(64,9%) patients. In all cases the histology of LR had no difference to the primary tumor. The aggressiveness of the local recurrence could be separated on 4 Degree of Aggressiveness - DА1, DА2, DА3, DА4. The statistical analysis showed that there is correlation between DALR and the size of LR, and the DALR rises with the increasing of the size of LR. To prove that and in the same time to make correct statistical analysis we joined stages DA1 and DA2 in group 1 and stages DA3 and DA4 in group 2. The analysis showed that group 1 correlates with approximate size of the process up to 6.5cm and group 2 correlates to approximate size of the process more than 6,5cm. In order to have exact reflection of absence or presence of lymph node metastases or distant metastases we adapted the DALR to TNM 2002, and formed 3 stages of LR. According to the TNM 2002 our DALR staging was: DA1= T1 - LR with maximal size ≤ 6,5 см, limited to the ispilateral renal fossa, DA2 = T2 - LR with maximal size ≤ 6,5 см, with infiltration of LR to the adjacent tissues and organs. DA3 = T3 - LR with size ≥ 6,5 см, with infiltration of LR to the adjacent tissues and large blood vessels. DA4 = T4 - LR with size ≥ 6,5 см, with infiltration of LR to the adjacent tissues, large blood vessels and distant organs and systems. According to the DALR system, we separated our patient in 3 staging groups - Stage of DALR: DA Stage I - DA1, DA2, N0, M0; DA Stage II - DA1, DA2, DA3, N1, M0; DA Stage III - Any DA, Any N, M1 In our study the distribution of the patients according to DALR was as shown: DА1-18(31,58%); DА2-15(26,32%); DА3-11(19,30%); DА4-13(22,80%). The patients were also staged as: DA Stage I-33(57,90%) patients; DA Stage II-15(26,32%) patients; DA Stage III-9(15,78) patients. Conclusions: Staging of LR after nephrectomy for RCC gives the clinician an opportunity for better preoperative assessment, as well as better defining of the disease prognosis. For the implication in practice and validation of this staging system, a multi center study involving larger number of patients must be conducted.
S128
One stage surgery for bilateral synchronous RCC – is it feasible for the patients?
Ormanov D.I.1, Georgiev M.I.1, Yanev K.P.1, Timev A.I.1, Dimitrov P.D.1, Vassilev V.D.1, Simeonov P.L.1, Kirilov S.P.1, Mladenov V.D.1, Atanassova S.S.1, Blazev D.T.1, Ormanov I.D.2, Panchev P.K.3 1 Medical University Sofia, Dept. of Urology, Sofia, Bulgaria, 2Al Rashid Hospital, Dept. of Urology, Kuwait, Kuwait, 3Medical University, Dept. of Urology, Sofia, Bulgaria
Eur Urol Suppl 2010;9(6):589
Evaluation of bcl-2 and P-53 markers as prognostic factors in patients with Clear Cell type renal cell carcinoma in patient undergone radical nephrectomy
Shahrokh H., Ajami H., Erfanian Daneshvar S. Hashemi Nejad, Dept. of Urology, Tehran, Iran Introduction & Objectives: To improve our understanding of the clinical relevance of p53, and bcl-2 proteins overexpression in clear cell type renal cell carcinoma ( ccRCC ), we retrospectively in a cohort group of patients investigated the immunohistochemical expression of p53, and bcl-2 and the relationship of this expression to clinicopathologic and prognostic characteristics. Material & Methods: The expression of p53 and bcl-2 was evaluated in 50 paraffin-embedded ccRCC specimens who has undergone radical nephrectomy in last 4 years in our center using immunohistochemistry.The clinical significance of these markers in relation to disease-specific survival and occurrence of metastasis or recurrence were analyzed. Patients followed up for 18 months (between 3 to 60 month).Variable factors including age, sex, tumor grade and stage, metastasis, recurrence and survival were analysed statistically in relation to the markers. Results: The expression of the p53 and bcl-2 protein was recognized in 12(25.5%) and 15(32.0%) cases, respectively; No correlation was noted between these two proteins and any clinicopathologic parameters, except bcl-2 expression and occurrence of metastasis.The detection level of p53 expression was consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl2 expression showed a correlation with probability of metastasis but could not be significantly correlated with other parameters and could not demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. Conclusions: Only bcl-2 attained independent prognostic significance in metastatic ccRCC. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC. Adjunctive use of bcl-2 and P-53staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC.At the present time, the combination of both tumor grade and stage represents the best prognostic markers available.
S125
Soluble CD30 as a predictor of acute renal allograft rejection
Kamali K. Hashemi Nejad Hospital, Dept. of Urology and Kidney Transplantation, Tehran, Iran Introduction & Objectives: Recent studies suggest that high pre and post renal transplant soluble CD30 levels may be associated with increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of serum sCD30 for prediction of acute graft rejection. Material & Methods: In this prospective study, we analyzed clinical data of 40 patients, whose pre and post transplant serum levels of sCD30 were detected by ELISA. Eight patients (20%) developed acute rejection (AR),12 patients showed delayed graft function (DGF) and 20 recipients experienced uncomplicated course group (UC) respectively. The patients were followed for 3 months and there was no death. Results: Preoperative sCD30 levels of three groups were 96.2±32.5, 80.2±28.3 and 76.8±29.8 U/ml, respectively (p=0.28).After transplantation significant decrease of sCD30 was detected in three groups on day 14 post-transplantation respectively (81.6±30.4, 63.2±28.5 and 55.5±27.7 U/ml respectively, p<0.001), while sCD30 levels of AR group remained significantly higher than DGF and non-rejecting patients(24.3±5.2,18.1±3.2 and 19.8±4.7 ng/ml respectively, p=0.02).Positive Panel reactive antibody(PRA)was not statistically different among groups(p=no significant).Also hemodialysis did not affect sCD30 levels(p=no significant). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 14 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 15 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Conclusions: Measurement of soluble CD30 on day 14 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.
S126
Chemotherapy with gemcitabine and 5 fluorouracil in patients with poor prognosis metastatic renal cell cancer – significant palliative role?
Janjic A., Bojanic N., Micic S., Vuksanovic A., Tulic C., Pejcic T. Urology Clinic Belgrade, Dept. of Urology, Belgrade, Serbia Introduction & Objectives: Determination of clinical resposnse rate of the
combination chemotherapy with weekly intravenous gemcitabine with 5 fluouracil ( 5FU) in patients with poor prognosis metastatic renal cell cancer ( RCC). Quality of life assessment prior and after cjemotherapy. Material & Methods: Between february 2007 and january 2010, 14 patients with metastatic RCC were enrolled onto this therapeutic protocol consisted of gemcitabine 1000mg/m2on days 1,8,15 and 5 FU 300mg/m2 on days 1 to 5 of a 28 days cicle. Patients had an ECOG performanse status of 0 to 3, with a median time since diagnosis of metastatic desease of 10 months. 10 patients ( 71.4%) had multiple metastatc sites and 4 patients had ( 28.5%) had massive locally advanced desease. Nephrectomy was performed in 12 patients and renal tumor biopsy in 2 . In all patients clear cell histology of RCC was defined with Fuhrman grades of 2 to 4. Minimal number of therapeutic cycles was 2, maximal 5 . Results: Of the all assessable patients, there were no complete resposnes, but 2 partial resposnes ( 14.2%) were detected. In 3 patients ( 21.4%) minor resposnes ( 25 to 50 % reduction in tumor size ) were observed.9 patients progressed ( 64.5%). The duration of resposnse in those 5 partial responses was 2,3,7, 8 and 14 months. The regimen was well tolerated, with fatigue,mucositis, nausea, vomiting, and grade 2 haematologic toxicities being the most common.Quality of life assessment was done with FACT G qustionnaire prior to chemotherapy and after completition of minimum 2 cycles of therapy, with average 43 points prior and 33 points after chemotherapy. Use of pain medication was less common during therapy. Conclusions: Weekly gemcitabine with 5 fluouracil is an active combination in patients with metastatic RCC.Therapy is wel ltolerated and produced an modest improvement in progression free survival with significant quality oflife benefits.
S127
Local recurrence in the renal fossa after nephrectomy for RCC
Yanev K., Ormanov D., Georgiev M., Dimitrov P., Vassilev V., Mladenov V., Simeonov P., Kirilov S., Timev A., Panchev P. Medical University Sofia, Dept. of Urology, Sofia, Bulgaria Introduction & Objectives: In the literature the frequency of local recurrence (LR) after radical nephrectomy for RCC varies between 0.77 to 4%. Based on our experience we created staging system of LR, based on TNM staging system and is in correlation with the Response Evaluation Criteria in Solid Tumors (RECIST-1). Material & Methods: For the period of 17 years (1992-2009) we had 1408 neprectomies for RCC. Of them 57 patients developed local recurrence. We implicated in practice two concepts – Degree of Aggressiveness of Local Recurrence (DALR) – which reflects the degree of invasion of the local recurrence in the adjacent tissues and Stage of DALR. Results: The cumulative incidence of LR in our study is 4.05%, but the real incidence drops to 1.77%, for those patients who had surgery in our department only. Of all cases of LR we operated 37(64,9%) patients. In all cases the histology of LR had no difference to the primary tumor. The aggressiveness of the local recurrence could be separated on 4 Degree of Aggressiveness - DА1, DА2, DА3, DА4. The statistical analysis showed that there is correlation between DALR and the size of LR, and the DALR rises with the increasing of the size of LR. To prove that and in the same time to make correct statistical analysis we joined stages DA1 and DA2 in group 1 and stages DA3 and DA4 in group 2. The analysis showed that group 1 correlates with approximate size of the process up to 6.5cm and group 2 correlates to approximate size of the process more than 6,5cm. In order to have exact reflection of absence or presence of lymph node metastases or distant metastases we adapted the DALR to TNM 2002, and formed 3 stages of LR. According to the TNM 2002 our DALR staging was: DA1= T1 - LR with maximal size ≤ 6,5 см, limited to the ispilateral renal fossa, DA2 = T2 - LR with maximal size ≤ 6,5 см, with infiltration of LR to the adjacent tissues and organs. DA3 = T3 - LR with size ≥ 6,5 см, with infiltration of LR to the adjacent tissues and large blood vessels. DA4 = T4 - LR with size ≥ 6,5 см, with infiltration of LR to the adjacent tissues, large blood vessels and distant organs and systems. According to the DALR system, we separated our patient in 3 staging groups - Stage of DALR: DA Stage I - DA1, DA2, N0, M0; DA Stage II - DA1, DA2, DA3, N1, M0; DA Stage III - Any DA, Any N, M1 In our study the distribution of the patients according to DALR was as shown: DА1-18(31,58%); DА2-15(26,32%); DА3-11(19,30%); DА4-13(22,80%). The patients were also staged as: DA Stage I-33(57,90%) patients; DA Stage II-15(26,32%) patients; DA Stage III-9(15,78) patients. Conclusions: Staging of LR after nephrectomy for RCC gives the clinician an opportunity for better preoperative assessment, as well as better defining of the disease prognosis. For the implication in practice and validation of this staging system, a multi center study involving larger number of patients must be conducted.
S128
One stage surgery for bilateral synchronous RCC – is it feasible for the patients?
Ormanov D.I.1, Georgiev M.I.1, Yanev K.P.1, Timev A.I.1, Dimitrov P.D.1, Vassilev V.D.1, Simeonov P.L.1, Kirilov S.P.1, Mladenov V.D.1, Atanassova S.S.1, Blazev D.T.1, Ormanov I.D.2, Panchev P.K.3 1 Medical University Sofia, Dept. of Urology, Sofia, Bulgaria, 2Al Rashid Hospital, Dept. of Urology, Kuwait, Kuwait, 3Medical University, Dept. of Urology, Sofia, Bulgaria
Eur Urol Suppl 2010;9(6):589