Sebastian W. Melchior

Conservative surgery of renal cell tumors in 140 patients: 21 years of experience.

Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation.

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.

A Clinical Trial With Chimeric Monoclonal Antibody WX-G250 and Low Dose Interleukin-2 Pulsing Scheme for Advanced Renal Cell Carcinoma

PURPOSE WX-G250 is a chimeric monoclonal antibody that binds to carbonic anhydrase IX(G250/MN), which is present on greater than 95% of RCCs of the clear cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the number of activated ADCC effector cells can be increased by a low dose interleukin-2 pulsing schedule, a multicenter study was initiated to investigate whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome in patients with progressive RCC. MATERIALS AND METHODS A total of 35 patients with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for ADCC capacity. Radiological assessment of metastatic lesions was performed at week 16 and regularly until disease progression. RESULTS A durable clinical benefit was achieved in 8 of 35 patients (23%), including 3 with a partial response and 5 with stabilization at 24 weeks or greater. Mean survival was 22 months. In general treatment was well tolerated with little toxicity. The number of effector cells increased during treatment but lytic capacity per cell did not increase. ADCC and clinical outcome did not appear to correlate. CONCLUSIONS WX-G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well tolerated. With a substantial clinical benefit and a median survival of 22 months in patients with metastatic RCC who have progressive disease at study entry combination therapy showed increased overall survival compared to WX-G250 monotherapy. Survival was at least similar to that of currently used cytokine regimens but with a favorable toxicity profile.

Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses.

PROTEOMEX, an approach which combines conventional proteome analysis with serological screening, is a powerful tool to separate proteins and identify immunogenic components in malignant diseases. By applying this approach, we characterized nine metabolic enzymes which were differentially expressed in renal cell carcinoma (RCC) cell lines and compared their expression profiles to that of normal kidney epithelium cells. Four of these proteins, superoxide dismutase (SODC), triosephosphatase isomerase (TPIS), thioredoxin (THIO) and ubiquitin carboxyl-terminal hydrolase (UBL1) were further analysed for both their constitutive and interferon (IFN)-gamma inducible protein expression pattern in cell lines or tissue specimens derived from RCC or normal kidney epithelium using Western blot analysis and immunohistochemistry, respectively. With the exception of the RCC cell line MZ1940RC, which completely lacks the expression of UBL1, a heterogeneous and variable expression pattern of the different metabolic enzymes was detected in RCC and normal renal epithelium. The highest differences in the expression levels were found for THIO in the RCC cell lines, which was 2-fold upregulated when compared to autologous normal kidney epithelium. Moreover, IFN-gamma treatment did not influence the constitutive expression of these metabolic enzymes. Thus, PROTEOMEX represents a valuable approach for the identification of metabolic enzymes which might be used as markers for the diagnosis of RCC.

Targeting of tumor associated antigens in renal cell carcinoma using proteome‐based analysis and their clinical significance

The suitability of proteome‐based strategies for the targeting of tumor‐associated markers along with further analysis regarding their clinical significance were investigated in human renal cell carcinoma (RCC). The immunogenic protein expression profile of normal kidney and RCC cell lines was studied by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, also termed PROTEOMEX. Employing this approach, a series of proteins reactive with either RCC patient sera and/or reactive with control sera were identified by microanalysis of tryptic peptides. Some of these candidate antigens represent members of the cytoskeletal family, such as cytokeratins, in particular cytokeratin 8, cytoskeletal tropomyosin, F‐actin capping protein, γ‐actin, stathmin, tubulin‐α, tubulin‐β and vimentin. The expression pattern and clinical significance of three of these antigens, namely cytokeratin 8, stathmin and vimentin, were further analyzed in a large series of surgically removed RCC lesions of distinct subtypes. A heterogeneous expression pattern of cytokeratin 8, stathmin and vimentin was demonstrated in the different RCC subtypes. All epithelial cells of the autologous normal kidney showed a strong cytokeratin 8 staining pattern, whereas they totally lack vimentin expression. Stathmin was expressed in 10% of tubule cells. In conclusion, PROTEOMEX could be employed for the identification of tumor‐associated antigens of the cytoskeleton which are differentially expressed in RCC of distinct subtypes as well as in normal renal epithelium.

Diagnosis and Surgical Management of Colovesical Fistulas Due to Sigmoid Diverticulitis

PURPOSE Diverticular disease of the colon is the most frequent cause of colovesical fistulas. In this study we evaluated the accuracy of different diagnostic procedures for the detection of colovesical fistula and the clinical outcome in a series of 49 patients who underwent surgery for colovesical fistula due to sigmoid diverticulitis. MATERIALS AND METHODS Between 1982 and 2007, 42 men and 7 women underwent surgery for colovesical fistula due to sigmoid diverticulitis. Preoperative diagnostic procedures included the poppy seed test, abdominopelvic computerized tomography, magnetic resonance tomography of the abdomen, cystogram, retrograde colonic enema, urethrocystoscopy and colonoscopy. RESULTS All patients had urinary tract infections and dysuria. Pneumaturia and fecaluria, which are pathognomonic symptoms of colovesical fistula, were present in 71.4% and 51.0% of the patients (35 and 25 of 49), respectively. Colovesical fistula was correctly diagnosed by the poppy seed test in 94.6% (35 of 37 examined patients) compared to abdominopelvic computerized tomography in 61.0% (25 of 41), magnetic resonance tomography in 60.0% (3 of 5), cystogram in 16.7% (5 of 30), retrograde colonic enema in 35.7% (15 of 42), cystoscopy in 10.2% (5 of 49) and colonoscopy in 8.5% (4 of 47). Patients underwent resection of the fistulized bowel, single stage bowel anastomosis without protective colostomy and closure of the bladder defect. Postoperative morbidity was 8.2% (4 of 49) and mortality was 0%. During a median followup of 68 months there were no recurrent fistulas. CONCLUSIONS In our series the poppy seed test had the highest sensitivity to detect colovesical fistulas. However, abdominopelvic computerized tomography, colonoscopy and cystoscopy are essential diagnostic procedures because the presence of colon or bladder cancer as an underlying cause of colovesical fistula will determine further therapy.

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

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.

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.

Urological De Novo Malignancy After Kidney Transplantation: A Case for the Urologist

PURPOSE The development of de novo malignancies is a well-known complication after renal transplantation. With increasing donor and recipient age the risk of post-transplant malignancy including genitourinary cancers is increasing. Thus, urologists have an increasing likelihood of treating these cases. We report our experience with the management of urological de novo malignancies after renal transplantation. MATERIALS AND METHODS Urological de novo malignancies developed in 29 of 802 patients after renal transplantation between 1988 and 2009. Data were analyzed for tumor incidence, treatment, followup and possible factors contributing to tumor development. RESULTS Patients had renal cell carcinoma (12 at a median of 46.5 months after renal transplantation), transitional cell carcinoma (6 bladder cases at 35 months, 2 renal pelvis cases at 37.5 months), carcinoma of the prostate (7 at 69 months) and seminoma (2 at 41.5 months). No treatment related graft losses occurred. Of 3 cases of renal cell carcinoma developing in the graft 2 were treated with nephron sparing surgery. CONCLUSIONS Urological post-transplant malignancies are an increasing problem for urologists. Regular surveillance after renal transplantation is mandatory to detect early occurrence of de novo malignancies and standard urological treatment principles can be applied. Nonfunctioning native kidneys with suspicious lesions should be removed early. Radical pelvic surgery after renal transplantation and nephron sparing procedures in the graft can be a challenge even for the experienced urologist, and require surgical versatility.

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.