[The "right" patient for implant surgery in urology : Why patient selection, informed consent, and communication are so important for patient satisfaction]. / Der "richtige" Patient für die Implantatchirurgie in der Urologie : Warum Patientenselektion, Aufklärung und Patientenkommunikation so wichtig für die Patientenzufriedenheit sind.

In implant surgery for erectile dysfunction and urinary incontinence, adequate patient selection is essential for postoperative therapy success. Several scientific studies report patient satisfaction rates for penile implants and artificial urinary sphincter implantation of over 90%. Nevertheless, studies also report, that between 5 and 30% of the patients are not satisfied with the result of their operation. Sufficient patient information and consent prior surgical procedure in urological prosthetics are a key determinant for later patient satisfaction and therapy success. Diligent assessment of realistic expectations, possible complications, and risks must be made. Unrealistic and exaggerated expectations need to be met and discussed with the patient. Therefore adequate physician-patient communication is essential. Especially in the case of surgical revision or for patients with risk factors, the probability of complications is higher and may significantly increase later dissatisfaction. Also, the involvement of the partner plays a major role in later patient satisfaction in urological implant surgery. Finally, there is a group of patients for which the risk of later dissatisfaction is particularly high. These are patients with compulsive/obsessive behavior, unrealistic expectations, patients after revision surgery, self-entitled patients, as well as those patients who deny the extent of their illness, visit multiple surgeons (surgeon hopping) or have psychiatric illnesses. These patients are referred to with the acronym "CURSED" patients.

[Incontinence surgery-quality criteria and structured follow-up]. / Inkontinenzchirurgie ­ Qualitätskriterien und strukturiertes Follow-up.

The following article summarizes the current evidence including postoperative success rates and complications for various surgical options in the treatment of urinary incontinence. Due to different inclusion criteria and inconsistent definitions of study endpoints, the analysis of available studies is difficult. Thus, comparative studies with new devices for established treatment options should be planned. Structured processes used in certified continence centers improve the quality of care. Furthermore by documenting relevant complications, comparisons of treatment results thus become possible and provide evidence for the use of different surgical options in the treatment of urinary incontinence.

Refinements in reconstruction of penile skin loss using intra-operative prostaglandin injections, postoperative tadalafil application and negative pressure dressings.

PURPOSE: Penile shaft skin defects represent demanding reconstructive tasks because a high degree of flexibility and stability of the skin grafts are essential to allow regular erections and sexual intercourse. METHODS: A new concept of tailoring skin grafts to the erect penis by intra-operative application of prostaglandin E1 and postoperative stabilisation by negative-pressure wound therapy and pharmacological expansion by tadalafil was tested on four patients with penile shaft skin defects. Graft take, stability, pliability, softness and aesthetic results were evaluated up to at least 12 months postoperatively. The ratio of the skin transplanted area in the non-erect compared to the erect penis (non-erect/erect ratio) and the ratio of the skin transplanted area in the erect penis at 12 months compared to intra-operatively (Post/Pre ratio) was determined to define the amount of graft contraction and flexibility. International Index of Erectile Function (IIEF)-5 scores were evaluated postoperatively. RESULTS: There were no complications. Graft take was 97, 100, 100 and 100%. Stable skin grafts were achieved after 2 weeks. Sexual intercourse was possible at 2-3 months. The Post/Pre ratio was between 81 and 87% and proves comparably mild contracture rates. The non-erect/erect ratio of 50-72% shows how significantly undersized penile shaft skin grafts are when adjusted to the non-erect penis and that an adequate flexibility for erections can be reconstructed. IIEF-5 scores proved regular potency in three patients; one patient was no longer sexually active. CONCLUSIONS: With the new concept of tailoring the skin graft to the erect penis, pharmacological expansion and external stabilisation by vacuum-assisted closure (VAC) dressing the difficult task of penile skin reconstruction can be facilitated, accelerated and the functional and aesthetic outcome improved compared to earlier efforts or to results presented in the literature.

A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells.

BACKGROUND: Although cancer of the prostate is one of the most commonly diagnosed cancers in men, no curative treatment currently exists after its progression beyond resectable boundaries. Therefore, new agents for targeted treatment strategies are needed. Cross-linking of tumor antigens with T-cell associated antigens by bispecific monoclonal antibodies have been shown to increase antigen-specific cytotoxicity in T-cells. Since the prostate-specific membrane antigen (PSMA) represents an excellent tumor target, immunotherapy with bispecific diabodies could be a promising novel treatment option for prostate cancer. METHODS: A heterodimeric diabody specific for human PSMA and the T-cell antigen CD3 was constructed from the DNA of anti-CD3 and anti-PSMA single chain Fv fragments (scFv). It was expressed in E. coli using a vector containing a bicistronic operon for co-secretion of the hybrid scFv V(H)CD3-V(L)PSMA and V(H)PSMA-V(L)CD3. The resulting PSMAxCD3 diabody was purified from the periplasmic extract by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA-expressing prostate cancer cells and PSMA-negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST) was used. For in vivo evaluation the diabody was applied together with human peripheral blood lymphocytes (PBL) in a C4-2 xenograft-SCID mouse model. RESULTS: By Blue Native gel electrophoresis, it could be shown that the PSMAxCD3 diabody is mainly a tetramer. Specific binding both to CD3-expressing Jurkat cells and PSMA-expressing C4-2 cells was shown by flow cytometry. In vitro, the diabody proved to be a potent agent for retargeting PBL to lyze C4-2 prostate cancer cells. Treatment of SCID mice inoculated with C4-2 tumor xenografts with the diabody and PBL efficiently inhibited tumor growth. CONCLUSIONS: The PSMAxCD3 diabody bears the potential for facilitating immunotherapy of prostate cancer and for the elimination of minimal residual disease.

Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature.

BACKGROUND: Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed "chronic periaortitis". OBJECTIVE: To determine the optimal therapeutic and diagnostic approaches to IAAA. METHODS: The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. RESULTS: The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. CONCLUSIONS: Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment.

Contractile effects of tacrolimus in human and rat isolated renal arteries.

1. We tested the vasoactive properties of the immunosuppressive drug FK 506 (tacrolimus) in preconstricted rat and human isolated renal arteries in vitro. 2. In rat renal arteries, tacrolimus (3, 10 microM) showed a direct and dose-dependent contractile effect by maximally 23 microm (10% of the noradrenaline effect), which was only observed in the presence of intact endothelium. Moreover, a lower concentration of tacrolimus (1 microM) potentiated pressor responses to the sympathetic neurotransmitter noradrenaline but not to ATP in this species. ATP- (0.01-10 microM) induced vasodilation was not affected by tacrolimus (1 microM). 3. In contrast, in human interlobar arteries, tacrolimus failed to induce direct vasoconstriction and did not significantly potentiate constrictor responses to noradrenaline. Acetylcholine-(1 microM) induced vasodilation was much smaller in human than in rat renal arteries suggesting the lack of functional endothelium in the human preparation. 4. The findings suggest that tacrolimus releases an endothelium-derived constricting factor in rat renal arteries to increase vascular tone and to potentiate pressor responses to noradrenaline. In human interlobar arteries, this effect of tacrolimus is not observed probably because of the absence of functional endothelium or the necessary mediator mechanism.

Comparison of the activation status of tumor infiltrating and peripheral lymphocytes of patients with adenocarcinomas and benign hyperplasia of the prostate.

BACKGROUND: The presence of lymphocytic infiltration in prostate carcinomas has been shown to have prognostic relevance. However, it is not yet clear if this infiltrate represents a tumor-specific activated cell population or not. Therefore, the aim of the present study was to characterize the activation status of freshly isolated tumor infiltrating lymphocytes (TIL) from prostate carcinomas (PCa) and benign hyperplasia (BPH) with respect to the mRNA expression of cytokines and apoptotic factors. METHODS: TIL were isolated from mechanically disaggregated tumor material by gradient centrifugation. The cells of the interphase were depleted from epithelial cells with anti-human epithelial antigen magnetic beads and then CD3(+)- lymphocytes were selected with magnetic beads against this determinant. In these pure lymphocyte preparations the mRNA expression of IL-1, IL-10, IFN-gamma, TNF-alpha, Fas and Fas ligand was determined by using a semiquantitative RT-PCR. Contamination with tumor cells was excluded by a PCR for PSA and PSMA. RESULTS: The CD3(+)-TIL from 21 patients with PCa and 20 patients with BPH expressed significantly higher levels of IL-10- and Fas ligand-mRNA compared to the autologous CD3(+)- PBL, whereas the expression of IL-1-, TNF-alpha- and Fas-mRNA was not different in either cell population. In contrast, the mRNA levels of IFN-gamma were significantly higher only in the CD3(+)-TIL from the carcinomas but not from the BPH compared to autologous CD3(+)-PBL. CONCLUSIONS: Since high levels of IFN-gamma have been reported to be produced by specifically lytic lymphocytes, our results suggest the presence of specifically activated TIL in the prostate carcinomas but not in the BPH, whereas inflammatory activated TIL are present both in the carcinomas and the BPH.

Construction and in vivo evaluation of an anti-PSA x anti-CD3 bispecific antibody for the immunotherapy of prostate cancer.

BACKGROUND: Cross-linking of tumor antigens with the T-cell associated CD3 antigen can be effectively achieved by bispecific monoclonal antibodies and lead to an increase in antigen-specific cytotoxicity in T cells. Because of the high organ specificity of the prostate specific antigen (PSA), a bispecific antibody (BiAb) directed against this antigen and CD3 may be a tool for a highly specific immune therapy of prostate cancer. METHODS: For generating BiAb, the quadroma technique was used. Binding properties both to CD3 and PSA were shown by flow cytometry with the CD3 expressing Jurkat cell line and fluorescein-labeled PSA. Specific tumor cell lysis was tested with the PSA expressing prostate carcinoma cell line LNCaP as target and interleukin-2 activated human peripheral blood lymphocytes as effector cells in a chromium-51-release assay. For in vivo evaluation of the BiAb, a nude mouse model was used. The mice were inoculated with LNCaP prostate carcinoma cells. Animals with growing tumors were treated with 100 micrograms BiAb and 5 x 10(6) effector cells. RESULTS: Three stable quadromas producing anti-CD3 x anti-PSA BiAb were established. From the culture supernatant of one quadroma, BiAb was separated by affinity chromatography and tested in vitro and in vivo for its ability to target effector T lymphocytes against appropriate tumor cells. In vitro, a specific lysis of PSA expressing prostate carcinoma cells was demonstrated. In vivo, a significant reduction in tumor growth (p < 0.05) could be shown in nude mice treated with BiAb and effector cells as compared to a group treated only with effector cells and an untreated control group. CONCLUSION: In the present study, an anti-CD3 x anti-PSA-BiAb was demonstrated to be effective against prostate carcinoma cells in vitro and in vivo. Therefore this BiAb may be a tool for the immunotherapy of prostate cancer.

Systemic and local immunomodulatory effects of intravesical BCG therapy in patients with superficial urinary bladder carcinomas.

PURPOSE: The aim of the present study was to elucidate whether only local, or also systemic immunomodulatory effects may be induced by intravesical BCG therapy of superficial urinary bladder cancer. MATERIALS AND METHODS: A total of 37 patients with stages Ta to T1b superficial transitional cell bladder carcinomas received 6 weekly BCG instillations after transurethral resection of the tumor. In a first group of 19 patients blood was taken before each BCG instillation and 6 weeks after the last one. In a second group of 18 patients blood and urine was taken before and 2, 6, and 24 hours after each BCG instillation. In the mitogen-stimulated whole blood cell cultures and in the urine samples the levels of the cytokines IL-1beta, IL-2, IL-10, TNF-alpha and IFN-gamma were determined by enzymoimmunological tests. Additionally, in all plasma and urine samples the levels of TNF-p75-receptor (TNF-p75-R) were measured. RESULTS: Comparison of ex vivo leukocyte cytokine production in the blood cell cultures of the patients of group I revealed no significant change in the levels of the cytokines. In contrast, TNF-p75-R plasma levels increased significantly during the experimental time of 12 weeks (p < or =0.01). In the blood cell cultures of the group II patients a different daytime variation of cytokine production was seen, compared to the 19 healthy controls. After BCG instillation the normal peak cytokine production in the evening was suppressed. A significant rise in plasma TNF-p-75-R levels was measured 24 hours after BCG instillation (p < or =0.05). In the urine of these patients significantly higher levels of all measured cytokines and TNF-p75-R were observed 6 to 24 hours after the instillation. CONCLUSIONS: The results suggest that besides the well known local immune activation, BCG instillation also leads to a modulation of peripheral immune mechanisms.

Long-term results of dorsal penile vein ligation for symptomatic treatment of erectile dysfunction.

About 20% of patients with erectile dysfunction do not react to intracavernous pharmacological treatment (SKAT) because of a cavernous leak. The first attempt to treat venous insufficiency goes back as far as the beginning of the century. Ligature and resection of the superficial and deep veins of the penis (DPVL) were performed in 122 patients (nonresponders to SKAT with a maintenance flow of less than 40 ml min-1). Twenty-four patients suffered from primary dysfunction and 98 from secondary dysfunction. The average age of the patients was 49 years, and the average duration of the preoperative erectile dysfunction 4.4 years. Postoperative follow-up was carried out for 70 months. In 98% of the patients, cavernosography revealed a dorsal leak. Twenty-six per cent had ectopic veins, 38% a leakage through the crural veins and 24% a glandular or spongiosal shunt. After the 70-month follow-up, only 14% of the 122 patients were able to achieve an adequate spontaneous erection and 19% also responded to SKAT. Depending upon the time elapsed since the operation, the rate of spontaneous reaction was reduced. It was found that younger patients with a short history of erectile dysfunction, no arterial cofactor, a maintenance flow of less than 100 ml min-1 and a severe dorsal leakage from a DPVL were the most likely to benefit from this procedure. Since degeneration of smooth muscle cells of the cavernosa is in most patients the cause of the venous leakage, penis vein surgery is to be regarded as symptomatic treatment.

Anastomotic stricture after radical prostatectomy. Incidence, findings and treatment.

OBJECTIVES: Stricture of the vesico-urethral anastomosis is a well-known complication after radical prostatectomy. Dilatation, stricture incision or resection have been proposed for endoscopic treatment. METHODS: In a retrospective study of 340 patients with prostatic cancer who underwent a radical retropubic prostatectomy from 1988 until 1996, we looked at the incidence of anastomotic strictures. RESULTS: An anastomotic stricture was found in 24 cases (7%) requiring endoscopic treatment. Based on prospective X-ray studies, we were able to show that the site of stricture is located below the bladder neck musculature in most cases well above the distal urethral sphincter and pelvic floor. No continence problems were encountered following structure resection in a follow-up of 12-72 months determined by a questionnaire and pad test. CONCLUSION: The transurethral resection of anastomotic stricture allows for a rather generous tissue resection, which is preferable to incision or dilatation in our hands.

Endoscopic treatment of reflux by subureteric collagen injection: critical review of 5 years' experience.

In the past decade, subureteric endoscopic injection of Teflon or collagen has been propagated as a safe and successful treatment for vesicoureteral reflux. In our center, from 1990 through 1995, 118 children and 5 adults with reflux and recurrent urinary tract infections were injected with cross-linked bovine collagen in an open, prospective study. Efficacy and safety were assessed 6 and 12 months after injection, and long-term (> or =3 years) results were available in 78 cases. The overall success rate was 58% (64% of ureteral units) free from reflux at 12 months and 54% (58%) after 3 years. Analysis of anatomic, urodynamic, and technical features showed the grade of reflux to be the best predictor of success or failure. When only primary low- and middle-grade reflux, without concomitant anatomic disorders, is considered, the long-term success rate rose to 69% (74% of ureteral units). In conclusion, subureteric collagen injection cannot ultimately replace the highly effective surgical reimplantation. However, the procedure offers a minimally invasive alternative in selected cases of mild reflux when conservative management is inadequate.

Digitization and postprocessing of plain-film radiographs for assessment of stone fragmentation after extracorporeal shockwave lithotripsy.

In 50 patients treated for urolithiasis by extracorporeal shockwave lithotripsy (ESWL++), the radiographs taken before and 1 day afterward were initially assessed by conventional radiography and subsequently after standardized digitization and postprocessing. Clinical outcome and passage of stone fragments were reevaluated 3 weeks after ESWL. Using specially developed software routines, new disintegration parameters could be obtained by detecting the number of relevant minima in light-intensity distribution along the length axis of the concrement in digitized images. Comparing the digitized images before with those after ESWL, the concremental surface and axial length in digitized images on average showed no statistically significant difference. However, the number of visually and automatically detected light-intensity minima of the concrement region in digitized images obtained 1 day after ESWL was significantly higher than prior to ESWL and correlated significantly with the number of fissure lines in the conventional images. These new features in digitized images showed a high sensitivity in predicting later passage of stone fragments. Moreover, in six of the seven patients without detectable fissure lines in the early conventional radiographs but obvious signs of concretemental disintegration 3 weeks after ESWL, there was an increase in the number of light-intensity minima in the digitized images 1 day after ESWL. Our findings indicate that this method of digitization and post-processing of radiographs may improve the assessment of ESWL effectiveness by improving standardization in the analysis of all surveyed parameters and by offering new relevant disintegration measures.

[The value of a new digital laser card for image/report documentation and transmission]. / Wertigkeit einer neuen digitalen Laserkarte zur Bild-/Befunddokumentation und Ubermittlung.

The capabilities of a patient-oriented digital optical laser-card for the documentation of the image/report unit and for image transmission were assessed. 150 conventional X-rays covering the fields of urology (n = 50), traumatology (n = 50) and orthopaedics (n = 50) were digitised using a CCD scanner and subsequently transmitted to an Image-Transfer Medium (ITM) and to an optical laser-card. The image quality for the detection of relevant diagnostic parameters was evaluated by 4 radiologists and one clinician of the corresponding specialty. Based upon a total of 4740 decision readings for each method, it was found that the optical laser-card reduced the image quality significantly (p < 0.01) in comparison to the digitised ITM images in all fields. Thus, a primary diagnostic statement cannot be made based upon the images of the optical card. However, concomitant documentation of the image and opinion on the card may be used for the transmission of the radiological report, especially to external referring institutions.

Penile venous surgery for cavernosal venous leakage: long-term results and retrospective studies.

From February 1987 to September 1991, 122 men with erectile impotence and confirmed cavernosal venous leakage underwent penile venous surgery. After a postoperative follow-up of 36 months, only 18.8% of the patients had satisfactory erections without further therapy. Another 32.5% postoperatively converted to responders to intracavernous injection therapy with vasoactive drugs. Therefore, a total of 51.3% benefitted from the operation. Dynamic pharmacocavernography proved to be the most important examination in terms of establishing indication and prognosis. According to our results, there are two basically different forms of cavernosal venous leakage with different postoperative outcomes: primary and secondary corporeal incompetence. In many cases, an arterial cofactor was determined.

[Uretero-arterial fistula. A rare cause of massive hematuria]. / La fistule urétéro-artérielle. Une cause rare d'hématurie massive.

Ureteroarterial fistulae is a rare condition, with less than 25 reported cases. We describe such a fistula in a young female patient, after radiation therapy for cancer of the cervix and rectovaginal and vesicovaginal fistulae requiring sigmoidostomy and an ureteroureterostomy after long-lasting ureteral intubation. Angiography demonstrated the fistula and the reflux of contrast medium up to the pyelocalyceal cavities, and allowed establishing the origin of the massive hematuria, which caused the patient's death.