Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy.

OBJECTIVE: To evaluate clinical predictors for Gleason score upgrade (GSU) in radical prostatectomy (RP) specimen, especially in patients with 'very' low risk PCA (T1c and biopsy Gleason score ≤6 and PSA <10 ng/ml and ≤2 positive biopsy cores and PSA density <0.15). PATIENTS AND METHODS: 402 consecutive patients undergoing RP between 2004 and 2006, including a subgroup of 62 patients with 'very' low risk PCA, were examined. Patients were categorized for clinically relevant GSU (defined as upgrade into a higher PCA risk category). Parameters including number of biopsy cores obtained, positive biopsy cores, prostate weight, PSA, DRE and pathology department were evaluated for their role as predictors. Furthermore, GSU in RP specimen was analyzed for its impact on pT-stage. RESULTS: Clinically relevant GSU occurred in 38.1% in the whole cohort and in 32.3% in the 'very' low risk PCA subgroup. Gleason score downgrade (GSD) occurred in 4.7%. Number of biopsy cores obtained and prostate weight were independent negative predictors of GSU in all 402 patients (P = 0.02 and P = 0.03, respectively). In the 'very' low risk group, only number of biopsy cores obtained revealed as an independent negative predictor of GSU (P = 0.02). PSA, DRE, number of positive cores or pathology department were not associated to GSU. In the 'very' low risk group, GSU was related with extracapsular tumor extension (P = 0.05). CONCLUSIONS: Clinically relevant GSU in RP specimen is still a challenging problem. Increasing the number of biopsy cores lower this risk significantly. GSD is rare and thus of minor importance for treatment decisions.

Single center comparison of anastomotic strictures after radical perineal and radical retropubic prostatectomy.

OBJECTIVES: To analyze the incidence and management of anastomotic strictures (ASs) after radical perineal prostatectomy (RPP) and retropubic prostatectomy (RRP) and to identify possible predisposing factors. METHODS: Between 1997 and 2007, we performed 866 RPP and 2052 RRP for localized prostate cancer. Median follow-up was 52 months (12-136). We analyzed preoperative serum prostate-specific antigen, prostate size, clinical and pathologic tumor stage, neoadjuvant hormone deprivation, previous transurethral resection of the prostate, transfusion requirement, anastomotic insufficiency, and acute urinary retention (AUR) and its subsequent management to identify possible predisposing factors for AS formation. RESULTS: The rate of AS after RPP and RRP was 3.8% (33/863) and 5.5% (113/2048), respectively (P = .067). In multivariate analysis, RRP was a statistically significant risk factor for AS (P = .0002). On survival analysis, the incidence of AS was lower for RPP as compared with RRP at median follow-up (P = .0229). Primary response to endoscopic AS incision or resection was 94% (31/33) and 72.6% (82/113) after RPP and RRP, respectively. On multivariate logistic regression analysis biopsy Gleason score, previous transurethral resection of the prostate, prostate volume, pathologic tumor stage and grade, transfusion requirement, AUR, and surgical technique were independent risk factors for the development of AS. An AS developed in 45.4% (20/44) and 10.9% (5/46) of the postoperative AUR cases treated with a suprapubic cystostomy tube and a transurethral Foley catheter, respectively (P <.05). CONCLUSIONS: ASs occur more frequently after RRP in comparison with RPP. Primary endoscopic AS incision or resection are both highly successful. Treating postoperative AUR with a suprapubic cystostomy poses a high risk for AS formation and should be avoided.

Urokinase-plasminogen-activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer.

OBJECTIVE To evaluate the expression of urokinase-plasminogen-activator receptor (uPA-R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis. PATIENTS AND METHODS In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA-R expression was detected by dual-immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow-up was initiated to detect tumour relapse (defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL). RESULTS Overall, there was expression of 'CK + uPA-R' in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high-risk cancer (P = 0.005). The relative risk for CK + uPA-R expression in the BM was 3.1 times higher in high-risk than in low-risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA-R expression in BM or PB. The PSA-recurrence free survival was significantly lower in patients with CK + uPA-R-positive BM cells (P = 0.01). CONCLUSION In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high-risk disease. All patients with a later PSA relapse had had uPA-R expression in their DTC from the BM. DTC with uPA-R expression was an adverse prognostic factor for prostate cancer.

C-kit and its ligand stem cell factor: potential contribution to prostate cancer bone metastasis.

The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion.

Renal tumour surgery in elderly patients.

OBJECTIVE: To analyse morbidity, renal function and oncological outcome in patients aged >or=80 years who had surgery for renal tumours, as in the elderly such surgery is controversial in relation to life-expectancy and other causes of death. PATIENTS AND METHODS: Between 1990 and 2006, in our institution 1625 patients had surgery to treat solid renal tumours suspected to be renal cell carcinoma (RCC); 62 (4%) were aged >or=80 years (mean 82.5), and 73% of these elderly patients had radical nephrectomy (RN) and 27% nephron-sparing surgery (NSS). RESULTS: The median (range) follow-up was 3.1 (0.2-14.1) years (89% of the patients). There was no perioperative mortality. There were only minor complications in 47% of patients, most (34%) being temporary increases in serum creatinine level. Histopathologically, 10% of the 62 patients had benign lesions and 90% had RCC. Of the 56 patients with RCC, the stage was pT1a in 34%, pT1b in 25%, pT2 in 5% and pT3 in 36%. For those treated with RN the median (range) serum creatinine level before and after RN was 1.0 (0.7-1.8) and 1.4 (1.0-2.8) mg/dL (P < 0.05), and for those treated with NSS were 1.1 (0.7-4.4) and 1.2 (0.7-4.8) mg/dL (not significant), respectively. The 5-year overall survival was 68% and the cancer-specific survival was 85%. CONCLUSIONS: Surgery for renal tumours is safe in elderly patients, with a low perioperative morbidity and a good overall survival rate. Patients should be selected carefully according to comorbidities, biological age and social support.

Extraprostatic spindle cell stromal tumor of the prostate: case report.

Several benign and malignant nonepithelial and stromal-like lesions arise in the prostate. Because such lesions are rare, their recognition is essential, because treatment and prognosis depend on an adequate pathohistologic classification. We report a case of an 83-year-old man with a stromal tumor of the prostate of uncertain malignant potential (STUMP). He presented with urinary retention and rectal constipation. On bimanual examination, a rectally and suprapubically palpable mass was found. Imaging studies revealed a 12 x 8 cm pararectal inhomogeneous mass of uncertain origin compressing rectum and urethra. The tumor was resected by a retropubic approach and examined immunohistochemically.

Small renal tumors: correlation of clinical and pathological features with tumor size.

PURPOSE: We analyzed the association between tumor diameter and pathological stage, histological subtype, tumor grade and the incidence of metastases in renal cell carcinoma with a diameter of up to 4 cm (clinical stage T1a). MATERIALS AND METHODS: We analyzed a consecutive series of 663 patients with renal tumors 4 cm or less who underwent surgery at our institution between 1990 and 2006. After excluding 115 patients (17.3%) with benign tumors 548 with renal cell carcinoma were included in the study. Tumor size on preoperative imaging was correlated with pathological stage, tumor grade, histological subtype and incidence of metastases at diagnosis. For data analysis tumors were stratified by tumor diameter into 3 groups, including 2 cm--99 patients with tumors up to 2 cm, 3 cm--234 with tumors between 2.1 and 3.0 cm, and 4 cm--215 with tumors between 3.1 and 4.0 cm in diameter. RESULTS: Median clinical diameter of renal cell carcinoma in the whole series was 2.93 cm (range 0.8 to 4.0). Tumor stage was pT1a, pT1b and pT3 in 84.5%, 8.0% and 7.5% of cases, respectively. Tumor grade was 1 to 3 in 24.5%, 65.0% and 10.6% of cases, respectively. The renal cell carcinoma histological subtype was clear cell carcinoma in 77.9% of patients, papillary carcinoma in 15.3% and chromophobe carcinoma in 6.8%. Advanced tumor stage (pT3) was found in 3.0%, 5.1% and 12.1% of the patients in the 2, 3 and 4 cm groups, respectively (p <0.05). Grade 3 was found in 7.1%, 9.0% and 14.0% of the patients in the 2, 3 and 4 cm groups, respectively (p <0.05). Metastases at diagnosis were found in 3.0%, 2.6% and 6.0% of the patients in the 2, 3 and 4 cm groups, respectively. CONCLUSIONS: Negative prognostic features increase with tumor diameter and they are associated with even small tumors. However, above a tumor size of 3.0 cm there is a sharp increase in the incidence of negative prognostic parameters. New diagnostic tests are warranted to better stratify patients with respect to treatment aggressiveness for small incidental renal tumors.

Bilateral synchronous sporadic renal cell carcinoma: surgical management, oncological and functional outcomes.

OBJECTIVE: To analyse the functional and oncological outcomes of surgical treatment of bilateral synchronous sporadic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between 1969 and 2006, 57 patients with bilateral synchronous sporadic RCC were identified from our kidney database. The mean (range) follow-up was 4.8 (0.1-23.8) years; 28 patients (49%) had radical nephrectomy (RN) and contralateral nephron-sparing surgery (NSS), and 22 (39%) had bilateral NSS. The oncological outcome and long-term renal function were analysed. RESULTS: After excluding four patients (7%) with bilateral benign renal tumours, six (11%) with metastatic bilateral RCC and three (5%) who had bilateral RN, the cancer-specific outcome was analysed. For 44 patients with bilateral RCC who had surgery with intent to cure and avoid dialysis, 13 (30%) had stage pT1a, 10 (23%) pT1b, nine (17%) pT2 and 12 (27%) pT3 disease. At 5 and 10 years, the cancer-specific survival rates were 86% and 75%, and the local recurrence-free survival rates were 87% and 80%. The median serum creatinine level at the latest follow-up was 1.18 mg/dL in patients after bilateral NSS and 1.40 mg/dL after unilateral NSS and contralateral RN (P < 0.05). CONCLUSIONS: These long-term data support the concept that NSS, whenever possible bilateral, is the treatment of choice for bilateral synchronous sporadic RCC. NSS provides adequate local tumour control and cancer-specific survival. Preservation of renal function is more efficient with bilateral NSS than with unilateral NSS and contralateral RN.

Long-term follow-up of submucosal tunnel and serosa-lined extramural tunnel ureter implantation in ileocaecal continent cutaneous urinary diversion (Mainz pouch I).

OBJECTIVE: To assess upper urinary tract complications and renal function in patients with a submucosal tunnel and serosa-lined extramural tunnel ureter implantation during the long-term follow-up of ileocaecal continent cutaneous urinary diversion (Mainz pouch I). PATIENTS AND METHODS: In all, 458 patients who had diversion with the ileocaecal pouch were analysed in a retrospective follow-up study. Uretero-intestinal implantation was done using a submucosal tunnel (ST) in 809 reno-ureteric units (RUs) and by the serosa-lined extramural tunnel (ET) technique in 74 RUs. The median age of the patients at the time of surgery was 47.1 years, and the median follow-up was 89.0 months. RESULTS: For the ST, there was anastomotic obstruction in 59 RUs (7.3%) at a median of 16.8 months after diversion; the obstruction-free intervals at 1, 5 and 10 years were 97%, 93% and 91%, respectively. Obstruction rates were 13.9% for previously dilated upper tracts and 17.1% in patients with a neurogenic bladder. Serum creatinine levels were < or =1.6 mg/dL in 97% of the patients at the latest follow-up. For ET, there was anastomotic obstruction in three RUs (4.1%) at a median of 17.2 months after diversion. Obstruction-free intervals at 1, 5 and 10 years were 100%, 96% and 96%. Preoperative dilation of the upper tracts did not reduce the obstruction rate (3.1%), but it was 7.1% in patients with a neurogenic bladder. Serum creatinine levels were < or =1.6 mg/dL in 98% of the patients at the latest follow-up. CONCLUSIONS: The ET gives lower obstruction rates than the ST, especially when upper tracts are dilated and in patients with a neurogenic bladder. Renal function remained stable with both techniques in the long term.

Long-term followup of the intussuscepted ileal nipple and the in situ, submucosally embedded appendix as continence mechanisms of continent urinary diversion with the cutaneous ileocecal pouch (Mainz pouch I).

PURPOSE: We analyzed stoma related complications and continence rates in patients who underwent continent urinary diversion with the cutaneous ileocecal pouch (Mainz pouch I). We compared the intussuscepted ileal nipple and in situ, submucosally embedded appendix as continence mechanisms. MATERIALS AND METHODS: A total of 401 patients were included in a retrospective followup study. Continence mechanisms were the intussuscepted ileal nipple in 205 patients and the in situ, submucosally embedded appendix in 196. RESULTS: A total of 144 patients (36%) required intervention for a stomal complication. Of patients who received an intussuscepted ileal nipple 34 (17%) had stomal stenosis at a mean time to first stenosis of 43.8 months, 41 (20%) had stones at a mean interval to the first stone of 62.8 months, 12 underwent reoperation for stomal incontinence, including 1 because of nipple necrosis, and 82% were completely continent. Of patients who received an in situ, submucosally embedded appendix 63 (32%) had stomal stenosis at a mean time to first stenosis of 31.4 months, 20 (10%) had stones at a mean interval to the first stone of 47.5 months, 3 underwent reoperation for stomal incontinence, 4 had appendiceal necrosis and 92% were completely continent. CONCLUSIONS: Of stomal complications 63% were treated endoscopically. The higher rate of stomal stenosis with the appendiceal stoma is most likely due to the smaller diameter of the appendix. The higher rate of stone formation in patients with the intussuscepted ileal nipple is related to metal staples. Continence rates of the 2 outlets are good with somewhat larger amounts of mucous secretion from the larger stoma of the intussuscepted ileal nipple.

Nephron sparing surgery for renal cell carcinoma with normal contralateral kidney: 25 years of experience.

PURPOSE: We report the long-term results of our consecutive series of 504 patients who underwent NSS for cancer suspicious, solid renal tumors in the presence of a normal opposite kidney at our institution since 1979. MATERIALS AND METHODS: A total of 715 patients underwent NSS since 1969, including 504 for an elective indication, that is with a normal opposite kidney. Of these patients 381 (75.6%) had RCC, 123 (24.4%) had cancer suspicious benign lesions, including 53 (10.5%) with oncocytoma, 33 (6.5%) with angiomyo(lipo)ma, 23 (4.6%) with a complicated cyst and 13 (2.8%) with other benign lesions. Of the 381 patients with RCC 283 (74.3%) had clear cell, 68 (17.8%) had papillary and 30 (7.9%) had chromophobic RCC. Mean tumor diameter was 3.0 cm (range 0.5 to 11.0). Mean followup was 6.77 years (range 0.2 to 24.1). The oncological outcome was studied, including pathological features associated with tumor progression. RESULTS: Estimated cancer specific survival rates at 5 and 10 years were 98.5% and 96.7%, respectively. Estimated survival rates free of distant metastasis at 5 and 10 years were 97.5% and 95.1%, respectively. Nine patients with localized RCC experienced local recurrence after NSS. Estimated survival rates free of local recurrence at 5 and 10 years were 98.3% and 95.7%, respectively. CONCLUSIONS: The long-term results of our series support the concept of organ sparing surgery for RCC in the presence of a normal opposite kidney with excellent long-term survival and a low tumor recurrence rate.

Lymph node metastases in non-muscle invasive bladder cancer are correlated with the number of transurethral resections and tumour upstaging at radical cystectomy.

UNLABELLED: The first paper in this section, from Mainz, attempts to identify the clinical variables associated with the prevalence of lymph node metastases in non-muscle invasive bladder cancer. The authors found that delay in cystectomy in this potentially dangerous type of tumour is to be avoided, with a higher incidence of lymph node metastases as the number of transurethral resections increases. A paper from Austria shows that in renal carcinoma the pT1 subdivision is associated with differences in conventional histopathology and expression of biomarkers. OBJECTIVE: To identify clinical variables associated with the prevalence of lymph node metastases (LNMs) in patients with non-muscle invasive transitional cell carcinoma (TCC) of the bladder treated with radical cystectomy. PATIENTS AND METHODS: Of 866 patients treated by radical cystectomy and pelvic lymphadenectomy between 1989 and 2002, 219 had non-muscle invasive TCC of the bladder. A retrospective evaluation of these patients included univariate and multivariate analyses of sex, age, number of transurethral resections of the bladder tumour (TURBTs), interval between first TURBT and cystectomy, adjuvant therapy, maximum histopathological tumour stage and grade at TURBT, and tumour upstaging in the cystectomy specimen. RESULTS: LNMs were diagnosed in 33 patients (15%). After multivariate analysis modelling, the number of TURBTs and tumour upstaging in the cystectomy specimen were correlated with the prevalence of LNMs at cystectomy. The number of TURBTs increased the prevalence of LNMs from 8% in patients with one TURBT to 24% in those with two to four TURBTs. Tumour upstaging in the cystectomy specimen increased the prevalence of LNMs from 4% to 36%. CONCLUSION: Inappropriate delay and inadequate staging of high-grade non-muscle invasive TCC of the bladder are to be avoided. The present multivariate analysis showed that the number of TURBTs and tumour upstaging in the cystectomy specimen correlated with an increased prevalence of LNMs.

Specific complications of radical perineal prostatectomy: a single institution study of more than 600 cases.

PURPOSE: Although groups at several institutions have long experience with radical perineal prostatectomy (RPP), only few reports of larger series describe associated complications, mostly without reporting management options in detail. We analyzed specific perioperative and postoperative complications of the perineal approach and management strategies thereof. MATERIALS AND METHODS: The medical records of 630 patients who underwent RPP between January 1997 and May 2003 were retrospectively reviewed in regard to complications and their management. Median followup was 8 months (range 1 to 68). RESULTS: Major complications requiring open surgical intervention were noted in 11 patients (1.7%) for a total surgical revision rate of 2.4% (15 of 630). Two patients with persistent urinary fistula required fistula excision and closure. Two patients with a rectocutaneous fistula needed temporary diverting colostomy. Three patients with a combined urinary and fecal fistula were treated with protective colostomy, fistula excision and the interposition of a tunica vaginalis graft. No further morbidity was observed in these patients. In 7 patients a subvesical hematoma was drained surgically, including 3 mentioned in whom a hematoma expanded into the urethral anastomosis. Minor complications, which could be successfully managed conservatively or with endoscopic interventions only, developed in 124 patients for a total rate of 19.7%. In the long term 9% of the patients experienced postoperative de novo changes in stool habits after RPP but only 2.7% reported distressing anal sphincter incompetence. CONCLUSIONS: RPP is a safe and reproducible procedure with low major complication and reintervention rates even in a training center setting with many involved surgeons. A subvesical hematoma should be revised early since it can be the origin of subsequent major complications.

Transitional cell carcinoma of the renal pelvis presenting as a renal abscess.

We report on a 76-year-old woman who was diagnosed with a primary renal abscess of the left kidney. After percutaneous drainage, no clinical improvement was observed. Surgical exploration and nephrectomy were performed. The histologic evaluation revealed an unsuspected transitional cell carcinoma of the renal pelvis, which had been misinterpreted as a primary renal abscess. Malignancy must be considered as an underlying cause for the formation of a renal abscess, especially if no other predisposing factors such as diabetes mellitus or urinary stones are present.