[Abdominal organ retrieval: strategies to improve quality]. / Viszerale Organexplantation: Maßnahmen zur Verbesserung der Qualität.

The blatant problem of organ shortage leads to an increasing acceptance of organs from extended criteria donors. This increases the importance of the process of organ donation and retrieval. A working group of representatives of Bavarian retrieval surgeons and the procurement organization German Foundation of Organ Transplantation (DSO) was initiated to develop consensus-based recommendations for quality improvements in the field of organ retrieval on the basis of regional data. The main aim was to professionalize retrieval teams by specified training standards and to define objective qualifications for retrieval surgeons. Initial measures of the working group included agreement on standardized retrieval techniques and improvement of documentation in terms of quality forms and the return rate of the forms. Quality data are being analyzed prospectively with a new categorization of complications. Communication among centers and teams and complication reporting has already been improved and initial structural changes have been set up.

Utility of immunohistochemistry markers in the interpretation of post-high-intensive focussed ultrasound prostate biopsy cores.

PURPOSE: To overcome the difficulties in the interpretation of postoperative tumor obtaining biopsy cores for patients who treated their prostate cancer with high-intensity focussed ultrasound (HIFU) therapy. METHODS: The H&E slides of 58 patients with residual prostate cancer after HIFU treatment were systematically reviewed. Correlation between the pathologist's findings and immunohistochemical expression of MIB-1, alpha-Methyl-Co-Racemase and 34ßE-12 staining was analyzed. RESULTS: Mean time from treatment to biopsy was 40.2 (8-208) weeks. The expert review of the H&E slides identified 40 patients with viable carcinoma in the post-HIFU biopsy cores. 18 patients were revised to necrosis-only-tumors. These biopsies were performed not later than 16 weeks after HIFU treatment (median 10.9 weeks, range 8-14). Both MIB-1 and AMACR staining displayed significant differential expression in viable carcinoma (p < 0.001) compared to necrosis tumors. Referring to viable carcinoma tissue, AMACR staining index was significantly rising, the longer treatment dated back from biopsy (p < 0.002). In this context, 34-ß-E12 stained negative through all tumor areas and positive in the majority (85%) of the surrounding non-neoplastic epithelium. CONCLUSIONS: AMACR and MIB-1 reliably differentiate viable carcinoma from a process of ongoing irreversible necrosis in early post-HIFU prostate biopsy cores and therefore proposed-in addition with 34 beta-E12-as useful markers exposing suspicious tumor foci in difficult cases.

[19th annual conference of the working group on kidney transplantation of the academy of german urologists : mainz, 10-12 november 2011]. / 19. Jahrestagung des Arbeitskreises Nierentransplantation der Akademie der Deutschen Urologen : Mainz 10. bis 12. November 2011.

The 19th Annual Conference of the Working Group on Kidney Transplantation (KTX) of the Academy of German Urologists took place on 10-12 November 2011 in Mainz. The main topics at the meeting were surgical and technical aspects, immunosuppressive therapy, transplant rejection, pregnancy, sexuality, and psychological conflicts of kidney transplant recipients. The speakers documented the pertinence of interdisciplinarity for KTX and were not only from the field of urology but also from anesthesiology, gynecology, surgery, dermatology, nephrology, radiology, and psychosomatic medicine. The Bernd Schönberger Prize was awarded at the end of the event.

[Value of radical oncological surgery in bilateral synchronous renal cell cancer and coincidental simultaneous prostate cancer]. / Die operative Strategie bei koinzidentem Auftreten eines bilateral synchronen Nierenzellkarzinoms und simultanen Prostatakarzinoms.

To date, the current literature does not report on oncological surgery in bilateral renal cell cancer and coincidental simultaneous prostate cancer. We present the case of a 66-year-old patient presenting as a challenge due to this oncological-surgical constellation. Based on the present case study and the postoperative follow-up, we discuss possible surgical strategies and demonstrate that, even in the case of multiple tumour locations, a satisfying oncological and functional long-term result is achievable.

Polymorphisms of human estrogen receptor (ER) gene alpha and beta in prostate cancer PC-EW and PC-OR cell lines.

BACKGROUND: Prostate cancer is the second leading cause of death among men in Western countries. Genetic alterations of the estrogen receptor gene are known to be indicative of a higher risk of this disease. The estrogen receptor gene is found as two subtypes, alpha and beta. In this study the estrogen receptor alpha and beta genes were tested in 2 human prostate cancer cell lines: the hormone-sensitive PC-EW and the hormone-independent PC-OR. MATERIALS AND METHODS: Genomic DNA was isolated from 2 cell lines from metastatic prostate adenocarcinoma in hetero-transplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 and intron 1 of the human estrogen receptor gene alpha, and exons 1-9 of estrogen receptor gene beta. RESULTS: No point mutations were detected in the ER gene subtypes of either cell line. Polymorphisms were found of ER-alpha in exon 1, intron 1, exon 3, 4, 5, intron 6 and exon 8 and of ER-beta in intron 2 and exon 9. CONCLUSION: Point mutations of ER-alpha and -beta are not necessary for metastatic prostate cancer, alterations in different areas of the ER genes are more often found. These polymorphisms are a part of many genetic influences that accumulate to contribute to men's overall risk for developing prostate cancer.

[Penoscrotal elephantiasis]. / Penoskrotale Elephantiasis.

Penoscrotal elephantiasis is not an uncommon clinical picture that may arise as a symptom of many diseases; it is usually a sequela of a recurring inflammatory process, eczema or malignancy. Elephantiasis often occurs after radical operations in the pelvic region. Displacement of lymphatic pathways leads to a local edema which over the course of time may lead to a considerable increase in volume of the patient's genitals or other affected parts. The diagnosis of elephantiasis is not difficult. It is much more difficult to determine which disease has caused the obstruction of the lymphatic pathways. If it is a reversible stage, the object of treatment is to remove the obstruction and reinstate the physiological lymph flow. Conservative measures such as administration of anti-inflammatory drugs and diuretics, physical measures such as baths, massage, elevation of the affected parts and treatment of the underlying disease may be considered. On progression to irreversible elephantiasis a chronic lymphatic edema occurs for which conservative measures will be unsuccessful. For cases where physical and anti-inflammatory measures are unsuccessful, excision and amputation of the affected penoscrotal region is recommended in order to eliminate the functional dysfunction. We report on two cases of penoscrotal elephantiasis, one in a child and the other in an adult man.

[Congenital cystic juvenile granulosa cell tumor of the testes. Scrotal space-occupying lesion in a male neonate]. / Kongenitaler zystischer juveniler Granulosazelltumor des Hodens. Skrotale Raumforderung beim männlichen Neugeborenen.

This article reports on a newborn with a scrotal space-occupying lesion and histologically proven granulosa cell tumor of the testes. A massive scrotal space-occupying lesion was diagnosed in a full-term male neonate with a birth weight of 2,260 g and body length of 45 cm. Sonography of the right testicle revealed a mass 6x6x4 cm in size which was multiply septate and cystic. The testicular parenchyma was poorly defined with a Swiss cheese appearance. Chemical analysis of blood serum evidenced normal levels of testosterone, beta-HCG, and inhibin B as well as physiologically a clearly elevated alpha-fetoprotein level at 35,350 ng/ml. Based on the clinical and sonographic findings of the right testicle, inguinal surgical exposure of the testes was undertaken. Since there was hardly any testicular parenchyma, we decided to perform high inguinal ablation of the right testicle. This case report confirms that congenital granulosa cell tumors usually exhibit benign behavior during the neonatal period.

[B-cell lymphoma of the testes]. / B-Zell-Lymphome des Hodens.

The occurrence of primary non-Hodgkin's lymphomas of the testes is described in just a few studies in the urological literature. The clinical symptomatology and especially the treatment concept for this relatively rare tumor entity are hardly discussed. Imaging diagnostics, e.g., with CT or MRI, play a decisive role in determining the diagnosis and whether a primary testicular disease is involved or a generalized systemic disease. In cases of primary B-cell lymphomas of the testes, a high inguinal orchiectomy should be performed for diagnostic and therapeutic purposes. The standard chemotherapy for aggressive non-Hodgkin's lymphomas is the CHOP regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. This article presents two adults aged 67 and 75 years with histologically proven B-cell lymphoma of the testes and discusses the characteristics of this relatively rare clinical picture as well as treatment and prognosis.

Prostate biopsy in the supine position in a standard 1.5-T scanner under real time MR-imaging control using a MR-compatible endorectal biopsy device.

Thirty-seven consecutive patients with elevated PSA levels and negative tumor prostate biopsies underwent a MR-guided prostate biopsy in a 1.5-T scanner in the supine position. After localization of suspected tumor areas using an endorectal coil and two body-phased array coils, the biopsy device was positioned without any repositioning of the patient. The biopsy device consisted of a mount, a ball joint, a positioning stage and an insertion stage with a needle guide, which was filled with a MR-visible fluid to control positioning of the needle using a balanced steady-state free precession sequence (TrueFISP) and a high-resolution turbo spin echo (T2-TSE) sequence. Core biopsies were taken manually in the magnet. The biopsy needle could be correctly positioned in all cases. Suspected lesions with a diameter > or =10 mm could be successfully punctured. Four to nine (mean = 6) biopsies were taken per patient. In 14 patients, prostate cancer was confirmed at histology. Twenty-four biopsies positive for cancer were performed in 14 patients. A correct correlation was found between the site of biopsy and histology. MR-guided prostate biopsy can be effective in increasing primary positive tumor biopsy results in patients with a history of negative tumor TRUS-guided prostate biopsies.

Does the distance to normal renal parenchyma (DTNRP) in nephron-sparing surgery for renal cell carcinoma have an effect on survival?

BACKGROUND: The effect of the distance to normal renal parenchyma (DTNRP) on survival after nephron-sparing surgery (NSS) for renal cell cancer (RCC) was analyzed. Additionally, the role of T-classification, tumor diameter and tumor grading was considered. PATIENTS AND METHODS: NSS was performed on 126 patients with RCC between 1988 and 2000. Eighty-six patients were submitted to annual follow-up. These 86 patients were sub-classified into statistical groups according to the distance to normal renal parenchyma (< or = 2mm; > 2mm - < or = 5mm; >5 mm), T-classification, tumor diameter (< or = 20mm; > 20mm - < or = 30 mm; >30 mm - < or = 50mm; > 50mm) and tumor grading. The effect of belonging to one of these groups on survival was analyzed using the Log-Rank-Test (SPSS; version 11.0) and the Kaplan and Meier survival data. The level of significance was set at p < 0.05. RESULTS: During the follow-up period, 4 patients died related to RCC and 15 patients died from other causes. The tumor-specific survival was 95.4%. At the end of 2002, the mean follow-up time was 5.5 years (range 0.1 - 14.7). None of the variables which had been analyzed in our statistical groups had an effect on the overall survival. CONCLUSION: The distance to normal renal parenchyma does not influence survival, suggesting an additional resection to be unnecessary even in cases where the DTNRP is reported by frozen section to be less than 2 mm. RCC up to 5 cn in tumor diameter can be safely removed by NSS, even in the presence of a functional intact contralateral kidney.

Radiochemotherapy after transurethral resection is an effective treatment method in T1G3 bladder cancer.

AIM: Conservative therapy using deep transurethral resection (TUR) followed by radiochemotherapy is a novel treatment strategy in stage TI grade 3 (TIG3) transitional cell carcinoma (TCC) of the bladder. The aim of this study was to present our long-term results of radiochemotherapy in T1G3 TCC patients. MATERIALS AND METHODS: A total of 64 patients with TIG3 TCC of the bladder underwent a TUR and a subsequent radiochemotherapy protocol at our institution. Following TUR, a median dose of 55.8 (range; 45-69.4) Gy radiation therapy was applied to the bladder, and simultaneous chemotherapy was initiated using cisplatin, carboplatin and/or 5-fluorouracil. After completion of the protocol, response was evaluated by repeat TUR, and check cystoscopies were performed at regular intervals. Median patient age was 66 (range; 30-82) years and median follow-up was 43.2 (range; 6-127) months. RESULTS: Complete response was achieved in 55 (90.2%) patients. Of the complete responders, 7 patients experienced a superficial (Ta, T1) recurrence and 8 patients had progression. In 8 patients with refractory superficial and invasive relapses, a salvage cystectomy was mandated. The overall progression rate was 14%. The overall and disease-free survival rates were 76% and 93%, respectively at 5 years. During followup, 4 patients suffered from reduced bladder capacity, and 2 patients underwent cystectomy due to shrinking bladder. CONCLUSION: Combined multimodality therapy is a safe and curative treatment option for patients with T1G3 TCC of the bladder in the hands of dedicated multimodality teams. Therefore, it is reasonable to justify radiochemotherapy combined with TUR in the first-line treatment of T1G3 tumors.

Combination of adenovirus-mediated thymidine kinase gene therapy with cytotoxic chemotherapy in bladder cancer in vitro.

We evaluated efficacy, toxicity and potential synergism of adenoviral-mediated thymidine kinase (tk)- ganciclovir (GCV) gene therapy in combination with 4 cytotoxic chemotherapeutic agents (doxorubicin, cisplatin, mitomycin C, and methotrexate) in 3 human bladder cancer cell lines. Cell lines were exposed to (1) 10 different concentrations of adenovirus expressing tk plus GCV; (2) 8 different concentrations of either doxorubicin, methotrexate, mitomycin C or cisplatin; or (3) combination treatment consisting of either low-, medium- or high-dose tk-GCV gene therapy plus 8 different concentrations of a single chemotherapeutic agent. Cell survival was determined using a MTT-based cell proliferation-assay. For most combinations, adding chemotherapy to tk-GCV gene therapy did not result in any therapeutic benefit. In some scenarios, we observed modest improvement with combinations of high-dose tk-GCV gene therapy and high-dose standard chemotherapy over tk-GCV monotherapy. Low concentrations of methotrexate enhanced the antitumor effects of low- and medium-dose tk-GCV gene therapy. Low level negative interference between tk-GCV gene therapy and chemotherapy occurred in some combinations but was overall negligible. In general, adding chemotherapy to tk-GCV gene therapy did not demonstrate significant therapeutic benefit in vitro. High doses of chemotherapeutic agents should be used in combination with tk-GCV gene therapy in order to take advantage of the occasional instance where modest improvement occurred with combination therapy. Additional studies exploring the role of methotrexate in enhancing the tk-GCV system are required. Investigation of other, potentially more synergistic chemotherapeutic agents in combination with tk-GCV is warranted.

Androgen receptor gene mutations do not occur in ovarian cancer.

Genetic alterations have been frequently found in ovarian cancer. There is some indirect evidence indicating that mutation of the steroid receptor genes may play a role in the carcinogenesis of ovarian cancer. Human androgen receptor (hAR) gene mutations have been found in up to 50% of hormone-relapsed prostate cancer. The role of hAR mutation and its association with decreased expression in ovarian cancer has never been elucidated. In this study mutations of hAR gene in 38 human ovarian cancer cell lines with different AR expression pattern were studied using SSCP. No mutation of the hAR gene was found. Mutation of hAR gene is an infrequent event and therefore unlikely to be involved in the development of ovarian cancer. The decreased expression of hAR in advanced ovarian tumor is not due to genetic aberration of hAR. Mutation screening of hAR may not provide any information for risk assessment of developing ovarian cancer.

PROGINS polymorphism of progesterone receptor is increased in female offspring with maternal exposure to diethylstilbestrol.

DES (Diethylstilbestrol) was used for the treatment of corpus luteum insufficiences in early pregnancy. Prenatal exposure to DES leads to an increased frequency of vaginal cancer in female offspring. DES causes persistent alterations of steroid hormone binding in the vaginal tissue. The frequency of a polymorphism (PROGINS) of human progesterone receptor (hPR) gene which is associated with an increased risk of sporadic ovarian cancer was tested in DES-exposed offspring with vaginal dysplasia. Genomic DNA was isolated from the serum of 15 US Caucasian DES-offspring. PROGINS analysis was performed using sequencing, gel-electrophoresis and SSCP-PCR. The results demonstrated that the frequency of PROGINS is increased in DES-offspring (DES: 6.7% homozygous, 26.7% heterozygous, normal US Caucasians: 3.3% homozygous, 15% heterozygous). Mutation screening of PROGINS is an important advantage for the clinical management of screening and can give additional information to prevent or find vaginal cancer in early stages in DES-offspring.

Comparison of long-term survival of cytomegalovirus promotre versus Rous Sarcoma virus promoter-driven thymidine kinase gene therapy in nude mice bearing human ovarian cancer.

The cytomegalovirus (CMV) promoter is considered one of the strongest positive regulators leading to expression of higher levels of the thymidine kinase (TK) enzyme than the Rous Sarcoma virus (RSV) promoter in vitro and in vivo. Cell killing efficacy of adenovirus-mediated CMV promoter-driven herpes simplex virus (HSV) TK gene therapy has been found to be 2 to 10 times more effective than RSV driven HSV-TK gene therapy in vitro. In this study the impact of CMV- versus RSV-driven HSV-TK gene therapy on long-term survival of nude mice bearing human ovarian cancer has been evaluated using a prospective randomized experimental design. The experiment was designed to show significance of survival differences from a 50% increase of survived days at a p-value of 0.05 with a power of 80%. All treatment groups showed an increase in median survival compared with control groups. Treatment benefit was ADV/CMV-TK vector dose dependent. At a given viral dose, no significant prolongation of survival was observed comparing CMV- and RSV-driven ADV-TK indicating that simply increasing cell killing efficacy in vitro above a minimal threshold level using a stronger promoter may not lead to prolongation of survival in the HSV-TK/GCV system.

Improvement of gene therapy for ovarian cancer by using acyclovir instead of ganciclovir in adenovirus mediated thymidine kinase gene therapy.

Adenovirus(ADV) mediated thymidine kinase(TK) gene therapy followed by ganciclovir(GCV) administration is widely used in different types of cancer. ACV shares the same mechanism of selective cell killing in ADV/TK positive cells as GCV and can be used at 4.5 times higher doses in patients without significant side effects. An increased dose of TK substrate is associated with improved bystander effect and more efficient cell killing. Toxicity and cell killing efficacy were assessed using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide(MTT) based assay in three ovarian cancer cell lines with different proliferation patterns. At the same concentration, equal or higher cell killing efficacy and bystander effect were observed using ACV rather than GCV. 2.5 and 5 times (25 micrograms/ml and 50 micrograms/ml) higher concentrations of ACV always resulted in more effective cell killing than GCV (10 micrograms/ml, P < 0.01). Our data indicate that replacing GCV with ACV in the ADV-TK gene therapy may increase the treatment effect without increasing toxicity.

The efficacy of adenovirus-mediated gene therapy of ovarian cancer is enhanced by using the cytomegalovirus promoter.

The cytomegalovirus(CMV) promoter is considered one of the strongest positive regulators. In this study toxicity, cell killing efficacy and bystander effect of Rous Sarcoma Virus(RSV) driven herpes simplex thymidine kinase(TK) gene therapy was compared with CMV driven TK gene therapy in three ovarian cancer cell lines with different growth patterns using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetra-zolium bromide (MTT) based assay. ADV/CMV-TK was shown to be 2 to 10 times more effective in tumor cell killing than ADV/RSV-TK. The difference in cell killing efficacy between ADV/CMV-TK and ADV/RSV-TK was dependent on the individual cell line. A CMV promoter dependent eight to ten fold improvement in cell killing efficacy was observed in the relatively slow growing SKOV3 cell line which is not easily transducible, while only a 2 to 4 fold difference was observed in the easily transducible OV-CA-2774 and OV-CA-1225 cell lines. ADV/CMV-TK also showed a stronger bystander effect than ADV/RSV-TK in all three ovarian cancer cell lines. Our data demonstrated that the efficacy of adenovirus-mediated gene therapy of ovarian cancer can be enhanced by using the CMV promoter without increasing toxicity.