- Email: [email protected]
171 TREATMENT OF URETERAL LESIONS WITH VERMIFORM APPENDIX: A REPORT OF 14 CASES
University Hospital of Toulouse Rangueil, Dept. of Urology and Andrology, Toulouse, France, 2University Hospital of Toulouse Larrey, Dept. of Endocrinology, Toulouse, France 1
Introduction & Objectives: Adrenal carcinoma (AC) is a rare malignant tumour, whose prognosis remains poor, and unchanged for 15 years. Our objective was to study the impact of the quality of the surgery on prognosis in patients operated for AC. Materials & Methods: In a series of 367 adrenalectomies carried out between 1996 and 2010, 17 had an AC (Weiss score above 3). In addition, we treated postoperatively 6 patients who had been operated for AC in other health facilities of our region. Post-operative management and follow-up were identical for all AC patients. Cases operated in our institution and elsewhere did not differ in socio-demographic variables (age, BMI, sex, size of the lesion) and diseases characteristics. Among the 23 AC, 2 were of stage I, 9 of stage II, 6 of stage III and 6 of stage IV. Fourteen (60%) were considered preoperatively as secreting. Surgery consisted of a laparoscopic adrenalectomy in 2 cases (8.5%), an open adrenalectomy in 11 cases (48%), associated with nephrectomy in 5 cases (22%), with nephrectomy and thrombectomy in 2 cases (8.5%), and with hepatectomy in 3 cases (13%). Surgical margins were positive in 7 cases (30%). Tumor extensions reached the liver in 3 cases, the kidney in 5 cases, and a tumoral thrombus was found in the vena cava in 2 cases. All alive patients were interviewed in August 2010. Survival was estimated using the Kaplan Meyer method, and comparisons between sub-groups using the log rank test. Results: During follow-up, 4 patients (17%) had a metastatic evolution, 6.25 ± 8.5 months (1-19) after the surgery. Seven patients (30%) had a local or remote recurrence, 12.7 ± 11.1 months (1-33) and 16.7 ± 19.8 months (4-60) after the surgery, respectively. The local recurrences were treated by surgery in 3 cases (2 nephrectomies and 1 lymphadenectomy) and radiotherapy in 1 case. Four patients with a metastatic evolution had a chemotherapy (36%) and the others mitotane only. At the date of the survey, 7 patients disease free with an average followup of 48.6 ± 36.4 months (5-114). Sixteen patients had died of their disease, the death occurring 25.67 ± 26.4 months (2-84) after the surgery. Prognostic factors of survival were the stage (log rank, p< 0.001), the Weiss score (log rank, p=0.002), the existence positive surgical margins (log rank, p< 0.001), having an age younger than 55 years (log rank, p< 0.001). The patients operated in other health facilities than the university hospital also had a lower survival rate (log rank, p=0.005). There was no difference according to the type of surgery difficulty of the surgery, blood loss, Op' DDD level, or the secreting character. Conclusions: In addition to the prognostic factors already highlighted (stage, histological score, positive margins, age), we observed that in AC, the quality of surgical management had a prognostic impact on the disease. These results plead for the management of these rare tumors in expert centers.
167
withdrawn
168
Determination of the best biochemical evaluation for the diagnosis of pheochromocytoma
Huyghe E. , Berbé J. , Hamdi S. , Bennet A. , Caron P. , Plante P. 1 University Hospital of Toulouse Rangueil, Dept. of Urology and Andrology, Toulouse, France, 2University Hospital of Toulouse Purpan, Dept. of Biochemistry, Toulouse, France, 3University Hospital of Toulouse Larrey, Dept. of Endocrinology, Toulouse, France 1
2
2
3
3
1
Introduction & Objectives: All available data concerning the biochemical dosages used for the diagnosis of pheochromcytoma were obtained in series of patients presenting with hypertension, and they almost always include extra-adrenal tumors (paraganglioma), whose secretion is different from pheochromocytoma. Nowadays, the major clinical presentation of pheochromocytoma is an incidentaloma. Therefore, we aimed at re-evaluating the diagnostic performances of the various dosages and combinations of dosages of catecholamines and metabolites. Materials & Methods: Design, setting and participants: one center cohort study of patients tested for suspicion of pheochromocytoma between 1998 and 2007. The analysis included 51 patients in whom we had at least one preoperative urine dosage of catecholamines and their metabolites prior to surgery. We divided the population into 2 groups, group 1 (n=38) with patients who had histopathological confirmation of pheochromocytoma and group 2 (n=13) with patients whose histology was different from pheochromcytoma. Main outcome measures: sensitivity and specificity, receiver operating characteristic (ROC) curves for each biochemical tests including adrenaline (A), noradrenaline (NA), dopamine (D), metanephrine (M) and normetanephrine (NM) and for all combinations of A, NA, M and NM by 2 or 3. The same measures were applied for subgroups with M and NM less than four times normal value (4N). Results: in group 1, all parameters were significantly higher than in group 2 (p<0.05). The higher sensitivity was for M (78.9%). All combinations of 2 tests gave a better sensitivity than M alone, ranging from 92 % for M+NM to 81.6% for A+NA. On the contrary, adjunction of a third dosage did not improve sensitivity except adjunction of A to M+NM that enabled a slight increase of sensitivity (+2%). Comparison of
the area under the ROC curve (AUC) for each test showed that M had the best concordance coefficient at 0.90. When Normetanephrine > 2400 μg/24h (4N) or Metanephrine > 1400 μg/24h (4N), sensitivity was 100%. For patients with M and NM < 4N, only NM and A were significantly higher in the group 1 than in group 2 (0.0026 and 0.018, respectively). The sensitivity of all tests decreased below 40%, except M (sensitivity: 64.3%). Among combinations of 2 tests, M + NA ranked first with a sensitivity of 78.6% and specificity at 100%. Compared to combinations of 2 dosages, combinations of 3 parameters enabled to increase sensitivity with sensitivity at 85.7% with A+NA+M, A+NA+NM and A+M+NM. Conclusions: We recommend to measure the level of urine M and NM at first and to prescribe a more thorough evaluation, including urine A and/or NA, if both M and NM are below 4 fold normal range. This strategy may be more cost effective and may improve the diagnosis of pheochromocytoma.
169
Management of Pelvic Fracture Urethral Distraction Defects (PFUDD) in a developing country
Hussain M., Rizvi S.A.H., Lal M., Askari S.H., Hussain Z. Sindh Institute of Urology and Transplantation, Dept. of Urology, Karachi, Pakistan Introduction & Objectives: Stricture clinic is the oldest clinic at our institute since 1972 where patient visit per year is 5760, and indoor admission of urethral stricture disease is 274. The gold standard of managing these patients is by suprapubic cystostomy followed by delayed urethroplasty but complications like restricture formation, erectile dysfunction, infertility and incontinence can occur post operatively which needs to be managed at an early stage. To report the results of management of PFUDD in adult patients with post operative complications and to high light the role of specialized clinic in early diagnosis and rehabilitation of these patients Materials & Methods: During the periods January 2000 to September 2010, 357 patients with (PFUDD) were managed by suprapubic cystostomy followed by excision and primary anastomosis by elaborated transperineal approach. Many patients were referred to us by past history of multiple failed procedures. After management all these patients were followed regularly in dedicated stricture clinic of institute for complications, uroflowmetry, urine culture and urethrogram. Those who found to have erectile dysfunction, infertility, stress incontinence were investigated by duplex ultrasound, semen analysis, urodynamics and were managed appropriately. Results: Out of 357 patients only 300 completed the follow up till October 2010, of these 59 (19.5%) developed recurrence of stricture and were treated by Dviu or urethral dilation, erectile dysfunction after urethroplasty was seen in 36 (12.5%), infertility in 89 (29.8%), retrourethral fistula in 1 (0.3%) and stress incontinence was seen in 3% while blood transfusion was needed in 12%. Operative time ranged from 2-5 hours and hospital stay was 3-7 days. Conclusions: Recurrence of stricture, erectile dysfunction, infertility remains the long term problem in these patients. Specialized referral centers and clinics are of great help to identify these problems at an early stage and rehabilitation of these young patients.
170
Change of renal function after renal injury: Long term follow up more than 10 years
Song J.H., Lee N.K. Medical College of Soonchunhyang University, Dept. of Urology, Cheonan, South Korea Results: Of the 272 renal injuries, 235 (86%) were managed nonoperatively. DMSA scans were obtained on average 11years after renal trauma. Mean decrease in renal function for grade III,IV and V renal injuries was 20%,32% and 70% respectively (Figure). Univarate analysis showed a significant relationship between renal function and AAST grade. Conclusions: This long term follow up study of renal injury shows that change in renal function in strongly correlated with AAST renal injury grade.
171
Treatment of ureteral lesions with vermiform appendix: A report of 14 cases
Komyakov B.K., Ochelenko V.A., Nikolaev N.M. Saint-Petersburg State Medical Academy of I.I. Mechnikov, Dept. of Urology, SaintPetersburg, Russia Introduction & Objectives: Ureteral reconstruction remains one of the most important problems of urology. The incidence of recurrent and complicated ureteral strictures increases but, results of reconstructive surgery are still poor. We believe that ureteral substitution with appendix is a perspective direction in this field of urology. Materials & Methods: From 1998 to 2010 we performed 14 ureteral substitutions with appendix. There were 13 (92.9%) females and only 1 (7.1%) male with a median age of 48±2.6 years (range from 28 to 71 years). Except of ureteral damage 1 female has uretero-vesical fistula and another one has uretero-cutaneous fistula. In 1 patient who developed ureteral stricture after gunshot wound, we performed
Eur Urol Suppl 2011;10(2):77
substitution of the upper third of the right ureter with appendix (uretero-appendicoureteroanastomosis). Another 13 patient had strictures of a lower part of ureter. They underwent ureteral reconstruction with uretero-appendico-cystanastomosis and 2 ureteral substitutions on the left. We performed a novel surgical technique for better appendicocystanastomosis in 8 patients -a flap was dissected from the dome of the cecum to increase diameter of anastomosis. Results: Early postoperative complications have occurred in 2 patients. They had attack of pyelonephritis and were treated conservatively. Late complications developed in 2 cases. 1 patient had stricture of ureteroappendicoanastomosis, which was treated with reanastomosis. Another one had ureteral twist. This patient underwent resection of ureter and reanastomosis. The follow up period range from 1 to 10 years (mean 8±1.6 years). Conclusions: The sufficient length and diameter of the appendix, comparable with ureter, mobile mesentery, sufficient blood supply and adequate peristalsis allows it to be appropriate option for ureteral substitution. We can to use appendix for reconstruction of any part of right ureter and lower part of left ureter.
Poster Session 15 UROTHELIAL TUMOURS: BASIC RESEARCH 1 Saturday, 19 March, 14.15-15.45, Hall H
172
Investigating the risk of bladder cancer among hereditary non-polyposis colorectal cancer (HNPCC) patients with confirmed mismatch repair (MMR) gene mutations
Skeldon S.C.1, Aronson M.2, Semotiuk K.2, Pollett A.3, Van Rhijn B.W.G.1, Bostrom P.J.1, Gallinger S.2, Cohen Z.2, Fleshner N.E.1, Jewett M.A.1, Hanna S.1, Kuk C.1, Van Der Kwast T.H.3, Evans A.3, Bapat B.2, Zlotta A.R.4 1 University Health Network, Princess Margaret Hospital, Dept. of Surgical Oncology, Urology, Toronto, Canada, 2Mount Sinai Hospital, Familial Gastrointestinal Cancer Registry, Toronto, Canada, 3University Health Network, Dept. of Surgical Pathology, Toronto, Canada, 4University Health Network, Princess Margaret Hospital, Mount Sinai Hospital, Dept. of Surgical Oncology, Urology, Toronto, Canada Introduction & Objectives: HNPCC is an autosomal dominant cancer syndrome caused by mutations in MMR genes. An increased risk for urothelial cell carcinoma (UCC) of the ureter and renal pelvis has previously been described in this population, specifically in those with MSH2 gene mutation. We have previously shown a link between MSH2 mutation and an increased risk of bladder cancer (BC). Here, we aim to confirm previous reports and identify a link between MSH2, upper urinary tract (UUT)-UCC and BC at the tissue level. Materials & Methods: The risk of BC and UUT-UCC was analyzed in MMR gene mutation carriers within the Familial Gastrointestinal Cancer Registry (FGICR) in Toronto, Canada. The pathology and histology was analyzed for screening and management recommendations. Data between 1970 to 2007 was obtained from the FGICR of 321 persons with known mutations (MLH1, MSH2, MSH6, PMS2). Among these, 177 patients had germline MSH2 mutations, while 129 patients carried MLH1 mutations. The standardized incidence ratios in Canada were used to compare cancer risk in patients with confirmed germline MMR mutations to the general population. Microsatellite instability (MSI) analysis and immunohistochemistry of the MMR proteins were also performed and compared to gender, stage and grade matched sporadic bladder tumours to provide a histological correlation. Results: Among 177 MSH2 mutation patients, BC was found in 11 (6.21%) patients but only in 3 of 129 patients (2.32%) with MLH1 mutations. No patients with germline MSH6 or PMS2 mutations had a diagnosis of BC. Of the 11 patients with MSH2 mutations, there were 5 men and 6 women, which is in contrast to the expected male to female ratio for BC of 3:1 in Canada. This 6.21% incidence of BC among MSH2 carriers is significantly increased compared to the lifetime risk seen in the general population in Canada. 9 of 11 tumours (81.8%) were MSH2 deficient on immunohistochemistry and 6 of these were MSI-H, 0% lacked expression of MLH1 while all matched sporadic cases displayed normal expression of MSH2 and MLH1. Among MSH2 carriers, UUT-UCC was found in 7 (3.95%) patients. All 7 tumours were found to be deficient in MSH2 expression and 5 of the 7 (71.4%) tumors were MSI-H. Conclusions: HNPCC patients with germline MSH2 mutations are at an increased risk not only for UUT-UCC but also for BC. Family members of germline MSH2 mutation carriers should be screened for urinary UCC by urinalysis and urine cytology. In addition, sporadic UUT-UCC diagnosed in patients under 60 years old or with a family history of HNPCC-related cancers should be screened for HNPCC by immunohistochemistry analysis of MMR proteins. Our study suggests that mutations of MMR genes may have an important contribution in the development of a subset of UCC.
173
MiRNA profile associated with response to neoadjuvant chemotherapy in patients with urothelial cell carcinoma
Gazquez C.1, Mengual L.1, Ribal M.J.2, Fernandez P.L.3, Lozano J.J.4, Alcaraz A.2 1 Hospital Clinic, Dept. of Laboratory of Urology, Barcelona, Spain, 2Hospital Clinic,
Eur Urol Suppl 2011;10(2):78
Dept. of Urology, Barcelona, Spain, 3Hospital Clinic, Dept. of Pathology, Barcelona, Spain, 4Hospital Clinic, CIBERehd. Bioinformatic Platform., Barcelona, Spain Introduction & Objectives: To analyze the miRNA expression profile of bladder cancer patients according to the response to neoadjuvant chemotherapy (NA CT), in order to select the differentially expressed miRNA between both groups and to identify a predictive miRNA panel of response to chemotherapy. Materials & Methods: A total of 81 patients with urothelial cell carcinoma of the bladder (UCC) whom received NA CT followed by radical surgery between 1991 and 2008 at the Hospital Clinic of Barcelona were identified. Of these patients, 10 responders and 10 non- responders to NA CT were analyzed in this analysis. RNA was extracted from the FFPE tissue blocks obtained in the TUR prior to the cystectomy by a commercial kit (RecoverAll Total Nucleic Acid Isolation, Ambion). Real Time Quantitative PCR (qRT-PCR) was performed using TaqMan Arrays containing 738 miRNAs. Results: Sixty three miRNAs were found differentially expressed between responders and non-responders to NA CT (p < 0.05). A miRNA panel containing 9 miRNAs (hsa-miR-17*; hsa-miR-193b; hsa-miR-200c*; hsa-miR-489; hsa-miR548b-5p; hsa-miR-548c-5p; hsa-miR-622; hsa-miR-744*; hsa-miR-886-5p) allows differentiating responders from non-responders to NA CT with sensibility and specificity of 100%. Furthermore, the study of the more differentially expressed miRNAs shows that some of them are related to other cancers. Conclusions: In this initial study we show that miRNA expression profile is able to differentiate between responders and non-responders to NA CT. With that knowledge, we built a miRNA set panel capable to identify those patients that will not respond to the treatment. However, a validation of this miRNA set panel in a larger series of patients, which is currently under investigation in our laboratory by using patient’s samples from 2 centres, is necessary before definitive conclusions can be drawn.
174
Identification of microRNAs epigenetically silenced in bladder cancer
Shimizu T.1, Suzuki H.2, Kitamura H.3, Yamamoto E.2, Imai K.4, Tsukamoto T.3, Toyota M.5 1 Sapporo Medical University School of Medicine, Dept. of Urology &Dept. of Biochemistry, Sapporo, Japan, 2Sapporo Medical University School of Medicine, First Dept. of Internal Medicine & Dept. of Biochemistry, Sapporo, Japan, 3Sapporo Medical University School of Medicine, Dept. of Urology, Sapporo, Japan, 4The University of Tokyo, The Institute of Medical Science, Sapporo, Japan, 5Sapporo Medical University School of Medicine, Dept. of Biochemistry, Sapporo, Japan Introduction & Objectives: Bladder cancer is the one of the most common malignancies in the urothelial tract. MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression post-transcriptionally, either by degradation of target mRNAs or by inhibition of protein translation. MiRNAs are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Recent studies have demonstrated a role of DNA methylation in silencing miRNAs in bladder cancer. The aim of current study is to identify bladder cancer-related miRNAs by screening epigenetically silenced miRNAs in bladder cancer. Materials & Methods: Two bladder cancer cell lines (T-24, UM-UC3) were treated with or without 5-aza-2’deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (4-PBA), and expression of mature miRNAs was examined using a TaqMan Low Density Assay System. We used UCSC genome browser to examine if CpG islands are located in the proximal upstream of the miRNAs upregulated after drug treatment. Methylation-specific PCR (MSP) and bisulfite pyrosequencing were carried out to analyze methylation status of the miRNA genes in bladder cancer cell lines and primary bladder cancer specimens. Results: Of 664 miRNAs examined, 208 miRNAs were up-regulated (>5-fold) in T24 cells, and 200 miRNAs were up-regulated in UM-UC3 cells, respectively. Among the miRNAs, 146 were commonly up-regulated in both T-24 and UM-UC3 cells. Among those 146 miRNAs, 36 miRNAs contain CpG islands in their 5’ end of the genes, and further analyzed. Methylation-specific PCR (MSP) was carried out, and 12 miRNAs showed aberrant methylation in bladder cancer cell lines. Bisulfite pyrosequencing of these 12 miRNAs was carried out, and we identified hypermethylation of 12 miRNAs in cultured and primary bladder cancer specimens. Conclusions: Our results suggest that DNA methylation is associated with miRNAs silencing in bladder cancer, and that these miRNAs may have a role in the development and progression of bladder cancer.
175
Simultaneous siRNA-mediated inhibition of the antiapoptotic factors BCL2, BCL2L1, BIRC5 and XIAP in bladder cancer cells
Kunze D., Kraemer K., Fuessel S., Grimm M.O., Wirth M.P. Dresden University of Technology, Dept. of Urology, Dresden, Germany Introduction & Objectives: An important event in tumor development is the deregulation of the apoptotic pathway which is mainly characterized by overexpression of the antiapoptotic genes BCL2, BCL2L1, BIRC5 and XIAP. The knockdown of these genes, e.g. by using siRNAs, may represent a promising approach in the treatment of bladder cancer (BCa).
Introduction & Objectives: Adrenal carcinoma (AC) is a rare malignant tumour, whose prognosis remains poor, and unchanged for 15 years. Our objective was to study the impact of the quality of the surgery on prognosis in patients operated for AC. Materials & Methods: In a series of 367 adrenalectomies carried out between 1996 and 2010, 17 had an AC (Weiss score above 3). In addition, we treated postoperatively 6 patients who had been operated for AC in other health facilities of our region. Post-operative management and follow-up were identical for all AC patients. Cases operated in our institution and elsewhere did not differ in socio-demographic variables (age, BMI, sex, size of the lesion) and diseases characteristics. Among the 23 AC, 2 were of stage I, 9 of stage II, 6 of stage III and 6 of stage IV. Fourteen (60%) were considered preoperatively as secreting. Surgery consisted of a laparoscopic adrenalectomy in 2 cases (8.5%), an open adrenalectomy in 11 cases (48%), associated with nephrectomy in 5 cases (22%), with nephrectomy and thrombectomy in 2 cases (8.5%), and with hepatectomy in 3 cases (13%). Surgical margins were positive in 7 cases (30%). Tumor extensions reached the liver in 3 cases, the kidney in 5 cases, and a tumoral thrombus was found in the vena cava in 2 cases. All alive patients were interviewed in August 2010. Survival was estimated using the Kaplan Meyer method, and comparisons between sub-groups using the log rank test. Results: During follow-up, 4 patients (17%) had a metastatic evolution, 6.25 ± 8.5 months (1-19) after the surgery. Seven patients (30%) had a local or remote recurrence, 12.7 ± 11.1 months (1-33) and 16.7 ± 19.8 months (4-60) after the surgery, respectively. The local recurrences were treated by surgery in 3 cases (2 nephrectomies and 1 lymphadenectomy) and radiotherapy in 1 case. Four patients with a metastatic evolution had a chemotherapy (36%) and the others mitotane only. At the date of the survey, 7 patients disease free with an average followup of 48.6 ± 36.4 months (5-114). Sixteen patients had died of their disease, the death occurring 25.67 ± 26.4 months (2-84) after the surgery. Prognostic factors of survival were the stage (log rank, p< 0.001), the Weiss score (log rank, p=0.002), the existence positive surgical margins (log rank, p< 0.001), having an age younger than 55 years (log rank, p< 0.001). The patients operated in other health facilities than the university hospital also had a lower survival rate (log rank, p=0.005). There was no difference according to the type of surgery difficulty of the surgery, blood loss, Op' DDD level, or the secreting character. Conclusions: In addition to the prognostic factors already highlighted (stage, histological score, positive margins, age), we observed that in AC, the quality of surgical management had a prognostic impact on the disease. These results plead for the management of these rare tumors in expert centers.
167
withdrawn
168
Determination of the best biochemical evaluation for the diagnosis of pheochromocytoma
Huyghe E. , Berbé J. , Hamdi S. , Bennet A. , Caron P. , Plante P. 1 University Hospital of Toulouse Rangueil, Dept. of Urology and Andrology, Toulouse, France, 2University Hospital of Toulouse Purpan, Dept. of Biochemistry, Toulouse, France, 3University Hospital of Toulouse Larrey, Dept. of Endocrinology, Toulouse, France 1
2
2
3
3
1
Introduction & Objectives: All available data concerning the biochemical dosages used for the diagnosis of pheochromcytoma were obtained in series of patients presenting with hypertension, and they almost always include extra-adrenal tumors (paraganglioma), whose secretion is different from pheochromocytoma. Nowadays, the major clinical presentation of pheochromocytoma is an incidentaloma. Therefore, we aimed at re-evaluating the diagnostic performances of the various dosages and combinations of dosages of catecholamines and metabolites. Materials & Methods: Design, setting and participants: one center cohort study of patients tested for suspicion of pheochromocytoma between 1998 and 2007. The analysis included 51 patients in whom we had at least one preoperative urine dosage of catecholamines and their metabolites prior to surgery. We divided the population into 2 groups, group 1 (n=38) with patients who had histopathological confirmation of pheochromocytoma and group 2 (n=13) with patients whose histology was different from pheochromcytoma. Main outcome measures: sensitivity and specificity, receiver operating characteristic (ROC) curves for each biochemical tests including adrenaline (A), noradrenaline (NA), dopamine (D), metanephrine (M) and normetanephrine (NM) and for all combinations of A, NA, M and NM by 2 or 3. The same measures were applied for subgroups with M and NM less than four times normal value (4N). Results: in group 1, all parameters were significantly higher than in group 2 (p<0.05). The higher sensitivity was for M (78.9%). All combinations of 2 tests gave a better sensitivity than M alone, ranging from 92 % for M+NM to 81.6% for A+NA. On the contrary, adjunction of a third dosage did not improve sensitivity except adjunction of A to M+NM that enabled a slight increase of sensitivity (+2%). Comparison of
the area under the ROC curve (AUC) for each test showed that M had the best concordance coefficient at 0.90. When Normetanephrine > 2400 μg/24h (4N) or Metanephrine > 1400 μg/24h (4N), sensitivity was 100%. For patients with M and NM < 4N, only NM and A were significantly higher in the group 1 than in group 2 (0.0026 and 0.018, respectively). The sensitivity of all tests decreased below 40%, except M (sensitivity: 64.3%). Among combinations of 2 tests, M + NA ranked first with a sensitivity of 78.6% and specificity at 100%. Compared to combinations of 2 dosages, combinations of 3 parameters enabled to increase sensitivity with sensitivity at 85.7% with A+NA+M, A+NA+NM and A+M+NM. Conclusions: We recommend to measure the level of urine M and NM at first and to prescribe a more thorough evaluation, including urine A and/or NA, if both M and NM are below 4 fold normal range. This strategy may be more cost effective and may improve the diagnosis of pheochromocytoma.
169
Management of Pelvic Fracture Urethral Distraction Defects (PFUDD) in a developing country
Hussain M., Rizvi S.A.H., Lal M., Askari S.H., Hussain Z. Sindh Institute of Urology and Transplantation, Dept. of Urology, Karachi, Pakistan Introduction & Objectives: Stricture clinic is the oldest clinic at our institute since 1972 where patient visit per year is 5760, and indoor admission of urethral stricture disease is 274. The gold standard of managing these patients is by suprapubic cystostomy followed by delayed urethroplasty but complications like restricture formation, erectile dysfunction, infertility and incontinence can occur post operatively which needs to be managed at an early stage. To report the results of management of PFUDD in adult patients with post operative complications and to high light the role of specialized clinic in early diagnosis and rehabilitation of these patients Materials & Methods: During the periods January 2000 to September 2010, 357 patients with (PFUDD) were managed by suprapubic cystostomy followed by excision and primary anastomosis by elaborated transperineal approach. Many patients were referred to us by past history of multiple failed procedures. After management all these patients were followed regularly in dedicated stricture clinic of institute for complications, uroflowmetry, urine culture and urethrogram. Those who found to have erectile dysfunction, infertility, stress incontinence were investigated by duplex ultrasound, semen analysis, urodynamics and were managed appropriately. Results: Out of 357 patients only 300 completed the follow up till October 2010, of these 59 (19.5%) developed recurrence of stricture and were treated by Dviu or urethral dilation, erectile dysfunction after urethroplasty was seen in 36 (12.5%), infertility in 89 (29.8%), retrourethral fistula in 1 (0.3%) and stress incontinence was seen in 3% while blood transfusion was needed in 12%. Operative time ranged from 2-5 hours and hospital stay was 3-7 days. Conclusions: Recurrence of stricture, erectile dysfunction, infertility remains the long term problem in these patients. Specialized referral centers and clinics are of great help to identify these problems at an early stage and rehabilitation of these young patients.
170
Change of renal function after renal injury: Long term follow up more than 10 years
Song J.H., Lee N.K. Medical College of Soonchunhyang University, Dept. of Urology, Cheonan, South Korea Results: Of the 272 renal injuries, 235 (86%) were managed nonoperatively. DMSA scans were obtained on average 11years after renal trauma. Mean decrease in renal function for grade III,IV and V renal injuries was 20%,32% and 70% respectively (Figure). Univarate analysis showed a significant relationship between renal function and AAST grade. Conclusions: This long term follow up study of renal injury shows that change in renal function in strongly correlated with AAST renal injury grade.
171
Treatment of ureteral lesions with vermiform appendix: A report of 14 cases
Komyakov B.K., Ochelenko V.A., Nikolaev N.M. Saint-Petersburg State Medical Academy of I.I. Mechnikov, Dept. of Urology, SaintPetersburg, Russia Introduction & Objectives: Ureteral reconstruction remains one of the most important problems of urology. The incidence of recurrent and complicated ureteral strictures increases but, results of reconstructive surgery are still poor. We believe that ureteral substitution with appendix is a perspective direction in this field of urology. Materials & Methods: From 1998 to 2010 we performed 14 ureteral substitutions with appendix. There were 13 (92.9%) females and only 1 (7.1%) male with a median age of 48±2.6 years (range from 28 to 71 years). Except of ureteral damage 1 female has uretero-vesical fistula and another one has uretero-cutaneous fistula. In 1 patient who developed ureteral stricture after gunshot wound, we performed
Eur Urol Suppl 2011;10(2):77
substitution of the upper third of the right ureter with appendix (uretero-appendicoureteroanastomosis). Another 13 patient had strictures of a lower part of ureter. They underwent ureteral reconstruction with uretero-appendico-cystanastomosis and 2 ureteral substitutions on the left. We performed a novel surgical technique for better appendicocystanastomosis in 8 patients -a flap was dissected from the dome of the cecum to increase diameter of anastomosis. Results: Early postoperative complications have occurred in 2 patients. They had attack of pyelonephritis and were treated conservatively. Late complications developed in 2 cases. 1 patient had stricture of ureteroappendicoanastomosis, which was treated with reanastomosis. Another one had ureteral twist. This patient underwent resection of ureter and reanastomosis. The follow up period range from 1 to 10 years (mean 8±1.6 years). Conclusions: The sufficient length and diameter of the appendix, comparable with ureter, mobile mesentery, sufficient blood supply and adequate peristalsis allows it to be appropriate option for ureteral substitution. We can to use appendix for reconstruction of any part of right ureter and lower part of left ureter.
Poster Session 15 UROTHELIAL TUMOURS: BASIC RESEARCH 1 Saturday, 19 March, 14.15-15.45, Hall H
172
Investigating the risk of bladder cancer among hereditary non-polyposis colorectal cancer (HNPCC) patients with confirmed mismatch repair (MMR) gene mutations
Skeldon S.C.1, Aronson M.2, Semotiuk K.2, Pollett A.3, Van Rhijn B.W.G.1, Bostrom P.J.1, Gallinger S.2, Cohen Z.2, Fleshner N.E.1, Jewett M.A.1, Hanna S.1, Kuk C.1, Van Der Kwast T.H.3, Evans A.3, Bapat B.2, Zlotta A.R.4 1 University Health Network, Princess Margaret Hospital, Dept. of Surgical Oncology, Urology, Toronto, Canada, 2Mount Sinai Hospital, Familial Gastrointestinal Cancer Registry, Toronto, Canada, 3University Health Network, Dept. of Surgical Pathology, Toronto, Canada, 4University Health Network, Princess Margaret Hospital, Mount Sinai Hospital, Dept. of Surgical Oncology, Urology, Toronto, Canada Introduction & Objectives: HNPCC is an autosomal dominant cancer syndrome caused by mutations in MMR genes. An increased risk for urothelial cell carcinoma (UCC) of the ureter and renal pelvis has previously been described in this population, specifically in those with MSH2 gene mutation. We have previously shown a link between MSH2 mutation and an increased risk of bladder cancer (BC). Here, we aim to confirm previous reports and identify a link between MSH2, upper urinary tract (UUT)-UCC and BC at the tissue level. Materials & Methods: The risk of BC and UUT-UCC was analyzed in MMR gene mutation carriers within the Familial Gastrointestinal Cancer Registry (FGICR) in Toronto, Canada. The pathology and histology was analyzed for screening and management recommendations. Data between 1970 to 2007 was obtained from the FGICR of 321 persons with known mutations (MLH1, MSH2, MSH6, PMS2). Among these, 177 patients had germline MSH2 mutations, while 129 patients carried MLH1 mutations. The standardized incidence ratios in Canada were used to compare cancer risk in patients with confirmed germline MMR mutations to the general population. Microsatellite instability (MSI) analysis and immunohistochemistry of the MMR proteins were also performed and compared to gender, stage and grade matched sporadic bladder tumours to provide a histological correlation. Results: Among 177 MSH2 mutation patients, BC was found in 11 (6.21%) patients but only in 3 of 129 patients (2.32%) with MLH1 mutations. No patients with germline MSH6 or PMS2 mutations had a diagnosis of BC. Of the 11 patients with MSH2 mutations, there were 5 men and 6 women, which is in contrast to the expected male to female ratio for BC of 3:1 in Canada. This 6.21% incidence of BC among MSH2 carriers is significantly increased compared to the lifetime risk seen in the general population in Canada. 9 of 11 tumours (81.8%) were MSH2 deficient on immunohistochemistry and 6 of these were MSI-H, 0% lacked expression of MLH1 while all matched sporadic cases displayed normal expression of MSH2 and MLH1. Among MSH2 carriers, UUT-UCC was found in 7 (3.95%) patients. All 7 tumours were found to be deficient in MSH2 expression and 5 of the 7 (71.4%) tumors were MSI-H. Conclusions: HNPCC patients with germline MSH2 mutations are at an increased risk not only for UUT-UCC but also for BC. Family members of germline MSH2 mutation carriers should be screened for urinary UCC by urinalysis and urine cytology. In addition, sporadic UUT-UCC diagnosed in patients under 60 years old or with a family history of HNPCC-related cancers should be screened for HNPCC by immunohistochemistry analysis of MMR proteins. Our study suggests that mutations of MMR genes may have an important contribution in the development of a subset of UCC.
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MiRNA profile associated with response to neoadjuvant chemotherapy in patients with urothelial cell carcinoma
Gazquez C.1, Mengual L.1, Ribal M.J.2, Fernandez P.L.3, Lozano J.J.4, Alcaraz A.2 1 Hospital Clinic, Dept. of Laboratory of Urology, Barcelona, Spain, 2Hospital Clinic,
Eur Urol Suppl 2011;10(2):78
Dept. of Urology, Barcelona, Spain, 3Hospital Clinic, Dept. of Pathology, Barcelona, Spain, 4Hospital Clinic, CIBERehd. Bioinformatic Platform., Barcelona, Spain Introduction & Objectives: To analyze the miRNA expression profile of bladder cancer patients according to the response to neoadjuvant chemotherapy (NA CT), in order to select the differentially expressed miRNA between both groups and to identify a predictive miRNA panel of response to chemotherapy. Materials & Methods: A total of 81 patients with urothelial cell carcinoma of the bladder (UCC) whom received NA CT followed by radical surgery between 1991 and 2008 at the Hospital Clinic of Barcelona were identified. Of these patients, 10 responders and 10 non- responders to NA CT were analyzed in this analysis. RNA was extracted from the FFPE tissue blocks obtained in the TUR prior to the cystectomy by a commercial kit (RecoverAll Total Nucleic Acid Isolation, Ambion). Real Time Quantitative PCR (qRT-PCR) was performed using TaqMan Arrays containing 738 miRNAs. Results: Sixty three miRNAs were found differentially expressed between responders and non-responders to NA CT (p < 0.05). A miRNA panel containing 9 miRNAs (hsa-miR-17*; hsa-miR-193b; hsa-miR-200c*; hsa-miR-489; hsa-miR548b-5p; hsa-miR-548c-5p; hsa-miR-622; hsa-miR-744*; hsa-miR-886-5p) allows differentiating responders from non-responders to NA CT with sensibility and specificity of 100%. Furthermore, the study of the more differentially expressed miRNAs shows that some of them are related to other cancers. Conclusions: In this initial study we show that miRNA expression profile is able to differentiate between responders and non-responders to NA CT. With that knowledge, we built a miRNA set panel capable to identify those patients that will not respond to the treatment. However, a validation of this miRNA set panel in a larger series of patients, which is currently under investigation in our laboratory by using patient’s samples from 2 centres, is necessary before definitive conclusions can be drawn.
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Identification of microRNAs epigenetically silenced in bladder cancer
Shimizu T.1, Suzuki H.2, Kitamura H.3, Yamamoto E.2, Imai K.4, Tsukamoto T.3, Toyota M.5 1 Sapporo Medical University School of Medicine, Dept. of Urology &Dept. of Biochemistry, Sapporo, Japan, 2Sapporo Medical University School of Medicine, First Dept. of Internal Medicine & Dept. of Biochemistry, Sapporo, Japan, 3Sapporo Medical University School of Medicine, Dept. of Urology, Sapporo, Japan, 4The University of Tokyo, The Institute of Medical Science, Sapporo, Japan, 5Sapporo Medical University School of Medicine, Dept. of Biochemistry, Sapporo, Japan Introduction & Objectives: Bladder cancer is the one of the most common malignancies in the urothelial tract. MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression post-transcriptionally, either by degradation of target mRNAs or by inhibition of protein translation. MiRNAs are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Recent studies have demonstrated a role of DNA methylation in silencing miRNAs in bladder cancer. The aim of current study is to identify bladder cancer-related miRNAs by screening epigenetically silenced miRNAs in bladder cancer. Materials & Methods: Two bladder cancer cell lines (T-24, UM-UC3) were treated with or without 5-aza-2’deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (4-PBA), and expression of mature miRNAs was examined using a TaqMan Low Density Assay System. We used UCSC genome browser to examine if CpG islands are located in the proximal upstream of the miRNAs upregulated after drug treatment. Methylation-specific PCR (MSP) and bisulfite pyrosequencing were carried out to analyze methylation status of the miRNA genes in bladder cancer cell lines and primary bladder cancer specimens. Results: Of 664 miRNAs examined, 208 miRNAs were up-regulated (>5-fold) in T24 cells, and 200 miRNAs were up-regulated in UM-UC3 cells, respectively. Among the miRNAs, 146 were commonly up-regulated in both T-24 and UM-UC3 cells. Among those 146 miRNAs, 36 miRNAs contain CpG islands in their 5’ end of the genes, and further analyzed. Methylation-specific PCR (MSP) was carried out, and 12 miRNAs showed aberrant methylation in bladder cancer cell lines. Bisulfite pyrosequencing of these 12 miRNAs was carried out, and we identified hypermethylation of 12 miRNAs in cultured and primary bladder cancer specimens. Conclusions: Our results suggest that DNA methylation is associated with miRNAs silencing in bladder cancer, and that these miRNAs may have a role in the development and progression of bladder cancer.
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Simultaneous siRNA-mediated inhibition of the antiapoptotic factors BCL2, BCL2L1, BIRC5 and XIAP in bladder cancer cells
Kunze D., Kraemer K., Fuessel S., Grimm M.O., Wirth M.P. Dresden University of Technology, Dept. of Urology, Dresden, Germany Introduction & Objectives: An important event in tumor development is the deregulation of the apoptotic pathway which is mainly characterized by overexpression of the antiapoptotic genes BCL2, BCL2L1, BIRC5 and XIAP. The knockdown of these genes, e.g. by using siRNAs, may represent a promising approach in the treatment of bladder cancer (BCa).