Paclitaxel-coated stents to prevent hyperplastic proliferation of ureteral tissue: from in vitro to in vivo.

Ureteric stents have become an indispensable tool in the armamentarium of every urologist. However, they carry their own morbidity resulting mostly from infectious or abacterial fouling and biofilm formation, and/or urothelial hyperplastic reaction. All of these may interact and lead to clinical complications. Many different stent designs and coatings have been proposed. In this study, we focused on the effect of paclitaxel-coated stents on hyperplastic proliferation of ureteral tissue, using as example anastomotic strictures after ureteroureterostomy in a rat model. Human urothelial cells (SV-HUC-1) were used to determine paclitaxel dosages in vitro. Polyurethane stents were coated with a paclitaxel containing biodegradable polymer and studied in a ureteroureterostomy rat model. 48 male 9-week-old Sprague-Dawley rats underwent either sham surgery (n = 16) or ureteroureterostomy with sutured anastomosis, and consecutive stenting with either a paclitaxel-coated or an uncoated stent (16 per group), respectively. The animals received daily intraperitoneal injections of 5-bromo-2-deoxyuridine (20 mg/ml, 100 mg/kg body weight) during the first eight postoperative days, and were sacrificed on day 28. Healing of the ureteral anastomosis and proliferation of urothelial cells was examined histologically and immunohistochemically. In vitro, a concentration of 10 ng/mm2 paclitaxel can be considered as non-toxic, while still exerting an anti-proliferative effect on urothelial cells. Histologically, typical wound healing processes were seen at the site of the ureteral anastomosis in vivo. Proliferation of urothelial cells was significantly lower in animals with paclitaxel-coated stents compared to those with uncoated stents (LI 41.27 vs. 51.58, p < 0.001). Our results indicate that stenting of ureteral anastomoses with paclitaxel-coated stents can reduce hyperplastic proliferation of ureteral tissue. Paclitaxel-coated stents thus might be able to prevent not only scar-induced postoperative stenosis after reconstructive surgery, but also hyperplastic urothelial reaction in non-anastomotic stent patients as part of their inflammatory response to the foreign material.

[Renal cell carcinoma diagnosis and prognosis within the context of the WHO classification 2016]. / Histopathologische Diagnose und Prognose des Nierenzellkarzinoms im Kontext der WHO-Klassifikation 2016.

BACKGROUND: Histological classification of renal cell carcinoma (RCC) has become more and more important for clinical management, but relatively few is known regarding the swiftness with which the 2016 World Health Organization (WHO) classification of RCC was adopted in the daily routine diagnostics. AIM: To retrospectively review the histological diagnosis of RCC within the context of 2016 WHO classification followed by survival analysis. MATERIAL AND METHODS: Retrospective register based analysis of RCC diagnosis between 1998 and 2017 and survival analysis. RESULTS: 1440 RCC cases were registered between 1998 and 1917. According to 2016 WHO classification, 77.7% clear cell RCC and 22.3% non-clear cell RCC were diagnosed. A total of 37 rare subtypes were recorded, among those 1% MiT family translocation RCC, 0.35% acquired cystic disease-associated RCC, 0.35% multilocular cystic renal neoplasm of low malignant potential, 0.35% collecting duct carcinoma, 0.3% mucinous tubular and spindle cell carcinoma, 0.1% clear cell papillary RCC and 0.1% RCC with (angio)leiomyomatous stroma. Cox regression analysis showed significant different overall survival and progression-free survival between the histological subtypes. DISCUSSION: The complexity of the 2016 WHO classification of RCC put high demands on histopathological diagnostics. At University Medicine Center Rostock morphological distinct RCC entities have been mostly diagnosed by conventional means via hematoxillin and eosin stained slides, but beyond immunohistochemistry additionally molecular techniques were established. The histologic subtyping of RCC according to 2016 WHO classification has prognostic significance and might have predictive significance for unique therapeutic approaches.

Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

[Allogeneic kidney transplantation. Preoperative, perioperative and postoperative management]. / Allogene Nierentransplantation. Prä-, peri- und postoperatives Management.

Allogeneic renal transplantation is the best treatment for many patients with chronic renal failure and end-stage kidney disease. Especially the health-related quality of life markedly improves after renal transplantation and the side effects of dialysis treatment as well as the progression of organ and tissue deterioration related to renal failure which are not treated effectively by dialysis are greatly reduced. To achieve good results of renal transplantation, however, the best possible preoperative as well as perioperative and postoperative conditions have to be established and patients on waiting lists need to be well prepared. Interdisciplinary patient care is needed before and after renal transplantation in order to achieve durable and long-term success of renal transplantation.

Putative biomarker genes for grading clear cell renal cell carcinoma.

OBJECTIVE: The initial objective of this renal cancer study was to identify gene sets in clear cell renal cell carcinoma (ccRCC) to support grading of ccRCC histopathology. MATERIALS AND METHODS: Preselected ccRCC tumor tissues of grade 1 (G1, n = 14) and grade 3 (G3, n = 15) as well es 14 normal kidney tissues thereof were subjected to microarray expression analysis using Human Genome U133 Plus 2.0 Array. Event ratio scoring, hierarchical clustering and principal component analysis were used to determine gene sets that distinguish expression profiles from normal kidney tissue, G1 and G3 tumor tissues. RESULTS: An initial set of 73 genes provided seven gene subclusters (SC01 to SC07) that distinguish RNA expression profiles from G1, G3 tumor and normal kidney tissues. A ranked list of 24 genes was determined that separated G1 from G3 tumors in high concordance with histopathological grading confirmed by immunohistochemical analysis of ceruloplasmin protein expression. CONCLUSION: A final set of 24 genes has been determined awaiting further validation on the RNA as well as on the protein level by studying an additional cohort of ccRCC patients. A reliable separation of G1 and G3 tumor grades will be instrumental to foster and direct the administration of upcoming targeted therapeutics of ccRCC tumors in a more predictive and reliable manner.

[Testicular metastases from prostate cancer]. / Hodenmetastasen eines Prostatakarzinoms.

Testicular metastases from prostate cancer is an uncommon occurrence and only 100 cases have been reported in the literature. Bilateral metastases are even more uncommon; however, testicular metatases may occur especially in cases of advanced prostate cancer. This article reports two cases with bilateral testicular metastases from prostate cancer.

Immunohistochemical expression of retinoblastoma protein and p16 in renal cell carcinoma.

INTRODUCTION: The regulation proteins retinoblastoma protein (pRb) and p16 play an important role in the cell cycle as tumor suppressors. pRb is the main substrate for the function of cyclin-dependent kinases during the cell cycle in the transition from G(1) to S phase. In this study, the immunohistochemical expression of pRb and p16 in renal cell carcinoma (RCC) were examined. METHODS: Paraffin-embedded specimens from 94 patients with RCC were examined immunohistologically, using primary antibodies for p16 and pRb (Novocastra) and a biotin-conjugated anti-mouse IgG secondary antibody. Microscopically, the expression of p16 and pRb was evaluated by examination of the staining intensity of 100 cells of each specimen, and compared with epidemiological parameters (tumor size, TNM, nuclear grade and follow-up). Statistical analyses were conducted by SPSS, version 15.0 (SPSS® Inc., Chicago, Ill., USA), the χ(2) test (Fisher's exact test), the Kaplan-Meier method and Mantel's log rank test. RESULTS: All 94 tumors showed a positive reaction for pRb (weakly positive in 67.0%; strongly positive in 33.0%). p16 was expressed in only 52.1% (weakly positive in 48.9%; intermediately positive in 3.2%; no strongly positive expression). The expression of p16-positive tumors was significantly associated with the expression of pRb (p = 0.040). Tumor size, grading, lymph node and distant metastases did not correlate with p16/pRb expression. CONCLUSION: pRb and p16 control the cell cycle as tumor suppressors. Therefore, in many tumors they are dysregulated. There are distinct differences in expression in various individual RCC. However, in a limited number of cases there was no significant correlation with clinical parameters.

Invasive zygomycosis in patients with graft-versus-host disease after allogeneic stem cell transplantation.

Invasive mold infections are a threat to immunosuppressed patients such as patients with graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Up to 10% of SCT recipients develop invasive aspergillosis (IA). Invasive zygomycosis (IZ) may occur during treatment against IA. Here we report 4 SCT patients with GVHD diagnosed with IZ. All patients had received myeloablative hematopoietic SCT and developed chronic GVHD requiring systemic immunosuppression. Underlying diseases were acute lymphocytic leukemia (2), osteomyelofibrosis, and multiple myeloma. All patients had developed pulmonary infiltration that led to initiation of antifungal therapy. Treatment for IA was voriconazole, caspofungin, or itraconazole. Organs involved with zygomycosis were lung, nasal sinus, skin, and kidney. Treatment with liposomal amphotericin and posaconazole was initiated in all patients, and 2 patients also had surgical debridement as well. Despite intensive treatment, no patient survived. IZ is becoming more common in patients with GVHD on successful treatment for IA. Even non-specific symptoms are suspicious in this group of patients and need to be evaluated by vigorous diagnostics. Despite effective antifungals and surgical intervention, the prognosis is grim in patients with active GVHD, as immunoreconstitution is mandatory for successful management.

Is there an emerging role for neoadjuvant targeted therapy in renal cell carcinoma?

The recent developments in the medical treatment of metastatic renal cell carcinoma have raised the question of the neoadjuvant use of targeted therapies in locally advanced renal tumours. Evidence at the level of case reports suggests that down-sizing of large renal carcinomas is feasible and small surgical series have so far shown that later surgical tumour removal is not impaired by neoadjuvant treatment. It is at present, however, far too early to fully assess whether such neoadjuvant treatment has an impact on patient survival or quality of life.

Traumatic penile injuries--mechanisms and treatment.

Injuries of the penis are uncommon but represent urological emergencies. We report 3 cases of penile trauma illustrating the diversity of penile injury presentation. Radiological investigations are only mandatory if there is any suspicion of a urethral injury. Primary surgical approach is recommended in cases of penile fracture or local wound infection. An immediate operative exploration with removal of hematoma and primary defect closure should be done in every case. Surgical management should not be delayed to avoid late complications.

Ovarian type surface epithelial carcinoma of the testis with delayed metastatic spread.

Ovarian type surface epithelial carcinomas of the testis and paratestis are rare. The most frequent form is the serous subtype while only a few cases of the mucinous subtype have been reported in the literature. A 67-year-old patient with a mucinous ovarian type surface carcinoma of the testis is presented. The histopathological and immunohistochemical details of this rare lesion are discussed.

[Gunshot wound to the kidney: case report and therapeutic management]. / Schussverletzungen der Niere : Fallbericht und Therapiemanagement.

Gunshot wounds to the kidney occur with different regional incidence. They are commonly combined with thoracic and abdominal injuries. Gunshot wounds may be caused by low-velocity or high-velocity bullets. The latter are usually used with military weapons and cause a higher degree of tissue damage. The therapeutic management of renal gunshot wounds has changed in recent decades resulting in more organ-preserving strategies. An imperative indication for surgical exploration of the kidney is critical renal bleeding with symptoms of hypovolaemic shock. We report the case of a 23-year-old male admitted to the hospital with combined gunshot wounds from a small-bore weapon with damage of the liver, stomach and the left kidney. There were no signs of thoracic injuries. The patient underwent transabdominal exploration with treatment of the liver and stomach lesions, removal of the bullet and preservation of the left kidney. A percutaneous nephrostomy and drainage of the retroperitoneal region were inserted; antibiotic prophylaxis was given. A 4-week postoperative intravenous pyelogram showed complete integrity of the upper left tract and good renal function.

[Genitourinary manifestations of lymphoma]. / Urogenitale Lymphommanifestationen.

Non-Hodgkin lymphoma (NHL) of the genitourinary system is a very rare disease. Only 1 % of NHL are primary genitourinary lymphomas, most commonly of testicular origin. Secondary infiltration from disseminated lymphoma can be found in all the genitourinary organs. We report on five patients with genitourinary lymphoma who were diagnosed at our department: one case of primary testicular lymphoma and four patients with secondary lymphomatous infiltration of kidney, bladder, prostate and testicles, respectively. The clinical courses are described and the current literature is reviewed. The operation could be restricted to a biopsy for assurance of the diagnosis. However, the mostly radical procedures are performed for curative purposes after an incorrect diagnosis of a malignant organ cancer without even recognizing or considering NHL in the differential diagnosis.

[Total infarction of the penis caused by entrapment in a plastic bottle]. / Totale Penisinfarzierung durch Strangulation in einer Plastikflasche.

Penile strangulation injuries are rare emergency situations, but need a fast urological emergency management for decompression of the penis and for removing of the foreign bodies. Strangulation objects can be metallic or non-metallic objects and are usually used for erotic or autoerotic purposes, for masturbation or increasing erection. We report a case of a 62-year old male with a total infected gangrene of the penis caused by a strangulation of a plastic bottle neck which continued 14 days. A total amputation of the penis was necessary. A perineal urethrostomy was performed as definitive urine diversion. Bacteriologic examination has identified Proteus mirabilis. Thus, a systemic antibiotic therapy was perioperatively applicated. The further course was uneventful with a secondary healing wound.

[Bladder rupture caused by spontaneous perforation of an infected urachal cyst]. / Blasenruptur durch spontane Perforation einer infizierten Urachuszyste.

Anomalies of the fetal urachus are rare. Normally, the postnatal urachus presents as a fibrous band extending from the bladder to the umbilicus. Urachal cysts may occur in postnatal life. Spontaneous perforation of urachal cysts is a very rare condition, which clinically may not be distinguishable from other acute abdominal conditions. We report a case of a 63-year-old male with a history of recurrent urinary tract infections and a bladder rupture caused by a spontaneous perforation of an infected urachal cyst. The symptomatology showed abdominal rigidity and pain, a palpable mass in the lower abdomen, and hematuria. Laboratory findings showed leukocytosis and an increased CRP level. The bladder rupture was confirmed by cystography. Bacteriologic examination identified Proteus vulgaris, Corynebacterium species, and Klebsiella pneumoniae. Most of the published cases in the literature report about intraperitoneal perforation of infected urachal cysts. In the present case, we found a spontaneous perforation of an infected urachal cyst leading to an extraperitoneal bladder rupture with an extraperitoneal limitation of the infection. The definitive therapy was complete surgical excision including a cuff of the bladder, drainage, and systemic broad-spectrum and local application of antibiotics. The further course was uneventful.