[Update of the German S3 guideline on renal cell carcinoma]. / Aktualisierte S3-Leitlinie Nierenzellkarzinom.

BACKGROUND: Renal cell carcinoma is the third most common tumor among urological tumors. In Germany more than 14,000 people are affected every year. The sex ratio is 2/3 men and 1/3 women. OBJECTIVES: The S3 guideline is intended to provide all disciplines dealing with renal cell carcinoma with the current status of diagnostics, therapy and follow-up care of the patients with this tumor. MATERIALS AND METHODS: The first version of the German guideline on renal cell carcinoma was published in 2015. The development was carried out at S3 level, which means that a structured, evidence-based literature search was carried out, recommendations and statements were developed in topic-related working groups and were approved by an interdisciplinary group of officials elected by the different medical societies. The chapters were gradually revised in 2017, 2020 and 2021 to reflect new aspects. This article provides information about the most important innovations of the most recent update from 2023. RESULTS: In the epidemiology subsection, the substance trichlorethene has been added as a risk factor for the development of renal cell carcinoma. While there were no new data on neoadjuvant therapy, the checkpoint inhibitor pembrolizumab was the first substance to demonstrate improved disease-specific and overall survival in the adjuvant situation. The combination nivolumab plus cabozantinib and lenvatinib plus pembrolizumab were included in the chapter on systemic therapy for metastatic clear cell renal cell carcinoma. New are the chapters on non-clear cell renal cell carcinoma and hereditary tumors. CONCLUSIONS: The S3 guideline provides a structured, evidence-based overview of all aspects of renal cell carcinoma.

[German expert consensus on programmed cell death ligand 1 (PD-L1) testing in perioperative systemic therapy of muscle invasive bladder cancer]. / Deutscher Expertenkonsens zur PD-L1-Testung ("programmed cell death ligand 1") in der perioperativen Systemtherapie des muskelinvasiven Blasenkarzinoms.

The risk of recurrence in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy depends on the pathological tumor stage. In particular, patients with lymph node metastasis (pN+), locally advanced (≥pT3), or residual muscle invasive tumor despite neoadjuvant chemotherapy are at high risk. Currently, the importance of adjuvant therapy with immune checkpoint inhibitors is increasing in the context of perioperative systemic therapeutic concepts. The indication for the PD­1 inhibitor nivolumab currently approved in the European Union requires testing of PD-L1 (programmed cell death ligand 1) protein expression by immunochemistry in tumor tissue. Focusing on MIBC patients at high risk of recurrence, new questions arise regarding the implementation and interpretation of PD-L1 testing. An interdisciplinary group of experts from Germany has discussed relevant issues from a clinicopathological point of view and developed practical recommendations to facilitate the implementation of validated and quality-assured PD-L1 testing for the approved indications in daily clinical practice.

[Algorithms for systemic therapy of prostate cancer, transitional cell carcinoma and renal cell carcinoma]. / Algorithmen zur Systemtherapie bei Prostata­, Urothel- und Nierenzellkarzinom.

Systemic therapy in uro-oncology is currently undergoing major changes. In the past, drug therapies only showed good treatment results in metastasized testicular tumors. New developments indicate that an improved understanding of tumor biology will lead to targeted treatment strategies for metastatic prostate, urothelial and renal cell carcinoma. In the following article, we summarize the practice-relevant innovations in systemic therapy in the guidelines on prostate cancer, transitional cell carcinoma of the bladder and renal cell carcinoma.

[Follow-up of renal cell carcinoma based on stage and initial treatment]. / Nachsorge beim Nierenzellkarzinom in Abhängigkeit des Stadiums und der erfolgten Therapie.

BACKGROUND: Renal cell carcinoma is the third most common tumor of the genitourinary system. Small tumors are increasingly treated by nephron-sparing surgery, focal therapy via cryoablation or radiofrequency ablation and also active surveillance. These treatment options are associated with increased follow-up care. OBJECTIVES: What are the current recommendations on follow-up care for different therapeutic approaches in renal cell carcinoma? MATERIALS AND METHODS: We analyzed different biological aspects regarding renal cell carcinoma, diagnostic procedures as well as recommendations of current guidelines (e.g. German S3, EAU AUA). RESULTS: Follow-up of renal cell carcinoma is not well standardized due to the limited amount of data. In general, follow-up should be intensified during the first 3 years following initial therapy as well as in patients with increased risk for tumor recurrence. For risk calculation different prognostic models based on clinical parameters have been published. CONCLUSIONS: Current recommendations on follow-up care in renal cell carcinoma are based on retrospective studies. Future strategies must include markers and be studied in a prospective manner.

[Immunotherapy and tyrosine kinase inhibitors in first-line treatment of metastatic renal cell carcinoma-Which strategy when?] / Immuntherapie und Tyrosinkinaseinhibitoren beim metastasierten Nierenzellkarzinom in der First-line-Therapie ­ Wann welche Strategie?

Immunotherapies with checkpoint inhibitors have led to a paradigm shift in metastatic renal cell carcinoma (mRCC) as they established a new standard in first-line treatment. In addition to the established monotherapy with tyrosine kinase inhibitors, the spectrum of first-line options has now become wider. Based on data from studies and current guideline recommendations, this article discusses possible factors for individual strategies in first-line treatment of mRCC. For this decision, the leading criterion is the patient's risk score. In addition, the efficacy and tolerability of the substances, tumor burden, patient age and preferences as well as considerations about sequence treatment can support the decision. Real-world data for the new combination treatment, biomarkers for personalized medicine as well as studies on optimal sequence treatment for mRCC are needed.

[Molecular tumor board-renal cell carcinoma]. / Molekulares Tumorboard ­ Nierenzellkarzinom.

The introduction of molecular targeted agents has fundamentally changed the treatment of metastatic renal cell carcinoma. A first wave of development was based on the improved understanding of tumor biology since the discovery of the importance of the von Hippel-Lindau gene as the key driver of the disease and paved the way for antiangiogenic agents. Of relevance is the overexpression of proangiogenic and proliferation-promoting factors (VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor) as well as an overactivation of the PI3K-Akt signaling pathway: the target structure is the "mammalian target of rapamycin" (mTOR) molecule, which is involved in the regulation of cell proliferative processes. VEGF-, PDGF-, and mTOR-signals and signaling pathways are central targets of current targeted substances. A second wave is certainly to be seen in the development of therapeutic approaches with the targeted activation and modulation of the immune system, which has brought "immunotherapy" back into the focus of interest. Central development is the application of immune-checkpoint inhibitors, with the help of which (re-)activation of the cellular defense, especially of T cells, takes place, which per se holds the potential of a cytoreductive therapy by killing the tumor cells. Even though the prognosis has improved significantly due to the rapid development of recent years, treatment remains challenging as most patients experience progress, and long-term survival is only achieved in about 20% of cases because some patients are primarily refractory or do not respond. The more intensive interlocking of molecular biology, pathology, clinical research, and interdisciplinary uro-oncology, as is the claim of molecular tumor boards, can contribute to the individual selection of a suitable therapy strategy and, thus, establish the latest findings and developments for the benefit of patients in the clinic.

[New drugs for metastatic kidney cancer]. / Neue Medikamente beim metastasierten Nierenzellkarzinom.

Systemic therapy of metastatic kidney cancer has undergone dramatic changes over the past years. One reason for this is our increasing knowledge of different histological subtypes and associated genetic aberrations. Furthermore, signalling pathways have been identified to be relevant for tumour progression and therapeutic intervention. Until some years ago, systemic therapy for kidney cancer consisted of cytokines. In this review, new drugs for the treatment of metastatic kidney cancer are discussed. These drugs predominantly interact the VEGF, EGFR and mTOR signalling pathways. Four drugs have been studied in phase III trials and were (or will soon be) approved for treatment of metastatic kidney cancer. Additionally, many drugs are currently being tested in phase I and phase II trials. At present, the following scenarios have an impact on therapy decisions: different prognostic groups, first-line and second-line therapy, combination therapies and the impact of different histological subtypes.

[Intravesical cidofovir--instillation therapy for polyomavirus-associated hemorrhagic cystitis after bone marrow transplantation]. / Intravesikale Cidofovir--Instillationstherapie bei Polyomavirus-assoziierter hämorrhagischer Zystitis nach Knochenmarktransplantation.

Viral infections of the urogenital tract are a potential problem in patients taking immunosuppressive medication. We report a 14 year old male patient with hemorrhagic cystitis who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia. Attempts at coagulation as well as instillation treatment and continuous bladder irrigation were not sufficient to stop bleeding. Sequential to these procedures, local instillation with cidofovir into the bladder was started to treat a suspected infection with polyomavirus and the gross hematuria stopped within a few days.

[Is there an indication for neoadjuvant or adjuvant systemic therapy in renal cell cancer?]. / Gibt es eine Indikation zur neoadjuvanten oder adjuvanten Systemtherapie beim Nierenzellkarzinom?

Looking at the most frequent urological tumors kidney cancer has the worst prognosis. Primary therapy consists of operative tumor removal in most cases. A tumor cutoff between 4 and 5 cm represents the turn towards a significant risk for postoperative tumor relapse. In those patients neoadjuvant or adjuvant therapy would be indicated. However, no phase III trials on neoadjuvant therapy of kidney cancer have been published in the literature. In contrast, five phase III trials on adjuvant therapy of kidney cancer have been published. In four trials interferon-alpha and/or interleukin-2 were applied. None of these trials had a positive outcome. Moreover, adjuvant cytokine therapy was associated with significant side effects in 30% of patients. In the fifth trial an autologous tumor cell vaccine (Reniale) demonstrated an improvement of progression-free survival and overall survival. Also, there were less than 1% side effects. Results from active trials investigating a combination of interleukin-2, interferon-alpha and 5-FU, or a heat shock protein vaccine or an antibody are awaited soon. New trials are testing tyrosine kidney inhibitors such as sunitinib and sorafenib.

[Localized amyloidosis of the ureter]. / Lokalisierte Amyloidose des Harnleiters.

Localized amyloidosis of the ureter is a rare condition. Because of the difficulty in differentiating between localized amyloidosis and an obstruction due to other benign or malignant conditions of the urinary tract, in some cases even an unnecessary nephroureterectomy is performed. We describe a patient with obstructive amyloidosis of the right ureter. Diagnosis was confirmed by endoscopy with biopsies. The patient was treated successfully by partial ureterectomy and ureteroneocystostomy. No systemic involvement of other organs was detected and after a 2-year follow-up no local recurrence developed.

[Spontaneous hemorrhage of the adrenal gland during pregnancy]. / Spontane Nebennierenblutung während der Schwangerschaft.

INTRODUCTION: Spontaneous hemorrhage is a rare cause of masses in the adrenal gland and must be differentiated from hemorrhage caused by trauma, neoplasm or metastases. CASE REPORT: A 41-year-old pregnant woman presented with nausea and right flank pain. Under suspicion of a pyelonephritis she was referred to the urological department with a normal obstetric evaluation. Ultrasound revealed an inhomogeneous mass above the right kidney, which seemed to be an abscess. An MRI scan showed an adrenal hemorrhage, but a bleeding caused by a neoplasm was excluded by a post-partum MRI control only. Upon conservative therapy the clinical condition improved and the parameters of inflammation normalized. There was no evidence of a hormone-producing adrenal tumor, an adrenal insufficiency caused by the hemorrhage, or a coagulopathy. CONCLUSION: Spontaneous hemorrhage in the adrenal gland is a rare condition in pregnancy. The diagnosis is confirmed by MRI. If conservative treatment fails, adrenalectomy will be necessary. Adrenal function should be controlled during pregnancy and post-partum. Recurrent hemorrhage and a neoplasm must be excluded by a post-partum MRI.

[Bone formation in the ureter. Osseous metaplasia of an obstructed ureter]. / Der Harnleiterknochen. Knöcherne Metaplasie eines obstruierten Harnleiters.

Bone formation outside the skeleton is well known. Yet, ossification within the urogenital tract is rare. The case of a patient with distal ureteral obstruction, hydronephrosis, and subsequent circular osseous metaplasia of the ureter is presented. Open transperitoneal right-sided nephrectomy with partial resection of the ureter was performed. Intraoperatively and in histopathologic examination circular bone formation adjacent to the ureteral wall was detected. There was no evidence of malignancy. Early animal experiments in the twentieth century showed that bone metaplasia may be induced by epithelium of the urinary tract under certain conditions such as ischemia, inflammation, necrosis, sclerosis, and trauma. Osseous metaplasia may therefore be considered a differential diagnosis of calcification of the upper urinary tract in the absence of urolithiasis.

[Penile skin necrosis after application of a ring and defect coverage by a skin mesh graft]. / Penishautnekrose nach Ringanlage und Defektdeckung mittels Spalthauttransplantation.

INTRODUCTION: Penile strangulations are rare and always need an individual emergency treatment. Functional impairment and loss of organ integrity are the most serious complications. CASE REPORT: A 43-year-old man came to our ambulance with a penile skin necrosis and a penile abscess. This was caused by a heating pipe that he had put on his penis six weeks ago. We first removed the pipe and performed a necrosectomy in a second step a skin mesh graft was applied. Six months later we observed a satisfactory cosmetic and good functional result. CONCLUSION: Even in serious penile injuries caused by strangulation a penectomy can be avoided by means of an individually planned emergency treatment.

[Postoperative polyuria after laparoscopic adrenalectomy for pheochromocytoma]. / Postoperative Polyurie nach laparoskopischer Adrenalektomie wegen Phäochromozytom.

Disturbances of osmoregulation leading to polyuria are well known complications after operations in the sella region. In contrast, increased urinary output following adrenalectomy is rare. We report a case of postoperative polyuria after laparoscopic adrenalectomy for pheochromocytoma with urine output up to 15 l per day. Treatment included careful monitoring of the patient and intravenous and oral replacement of fluids and electrolytes. In our case a normalisation of the urine output was observed after few days. A further treatment with vasopressin was not undertaken as the osmolality at all times was in normal range.

[Combination treatment with antisense oligonucleotides and chemotherapy in vitro]. / Kombinationsbehandlung mit Antisense-Oligonukleotiden und Chemotherapeutika in vitro.

Oncological therapy strategies are increasingly concentrating on the causal, molecular changes involved in carcinogenesis. So called "smart drugs" such as antisense oligoneucleotide (AsON) can be used as specific inhibitors of individual genes. AsONs have shown their effectiveness in many studies. Clinical studies have demonstrated, however, that for many tumours the inhibition of a single gene is, due to multigenetic alteration, largely ineffective. The combination of AsONs with conventional chemotherapeutic agents is currently being investigated in phase III studies. In these studies, chemotherapeutic agents have been evaluated in cell culture together with AsON against the proliferation associated Ki-67 gene, as well as against the apoptosis associated bcl-2 gene via RT-PCR, immunochemistry and MTT cell viability assay. For both AsONs, significant target inhibition was achieved in cell culture with a high target gene expression. The prior treatment of tumour cells with bcl-2 AsON significantly increased the effectiveness of chemotherapy, while the combination of conventional chemotherapeutic agents with Ki-67 AsON showed no synergistic effects.

[Vaccine therapy of prostate cancer]. / Vakzinetherapie des Prostatakarzinoms.

Vaccine therapy of prostate cancer has been increasingly studied in trials over the past few years. The different vaccine techniques are quite variable and are predominantly used in patients with advanced hormone-refractory prostate cancer. In this review, vaccine techniques using tumor cells, dendritic cells or poxvirus are analyzed. For theses approaches phase-III trials are being planned, have been initiated or are already completed. Many trials demonstrate the efficacy with regard to endpoints such as stimulation of the immune system and/or biochemical response and/or clinical response. Recently, one vaccine approach using autologous dendritic cells demonstrated a statistically significant prolongation of overall survival compared to placebo in patients with hormone-refractory prostate cancer. Side effects of vaccination are generally mild. At present, there are trials are being planned or are already ongoing that combine vaccine with other treatment strategies or enroll patients with earlier disease stages.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon-alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be administered as second-line options - for pazopanib the use is restricted to the event of cytokine failure. Everolimus (after TKI therapy) und sorafenib (after cytokines) are other compounds now available for second-line therapy. In addition, axitinib was approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial.The purpose of an interdisciplinary expert meeting held in 2014 was to debate about which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2012 conference provided the basis for the 2014 meeting 1. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.

Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy?

BACKGROUND: Hypertension is an important risk factor for the development of chronic graft failure and decreased graft and patient survival after renal transplantation. METHODS: Between September 1994 and August 1996, 14 patients underwent laparoscopic bilateral nephrectomy for treatment of drug-resistant hypertension after successful renal transplantation. Common causes of hypertension were largely excluded before bilateral nephrectomy. A scoring system was developed for comparison of different antihypertensive regimes. In this system, points were given according to type and dosage of each antihypertensive drug. RESULTS: At 6-month follow-up, all patients showed well-controlled blood pressure (median of mean arterial pressure: 104 vs. 130 mmHg preoperatively, P<0.001, n=14), and significantly fewer antihypertensive drugs were needed according to the scoring system (48.9+/-20.9 points vs. 105.9+/-23.5 points preoperatively, P<0.001, n=14). During laparoscopy, three conversions to open surgery were necessary. Postoperatively, four complications occurred. After laparoscopy, immunosuppression and other oral medication were given continuously. The hospital stay ranged between 3 and 6 days (median: 5 days). CONCLUSIONS: The results indicate that bilateral nephrectomy using the laparoscopic technique can be an effective alternative method for a selected group of patients with severe hypertension, which is unresponsive to conservative management after successful renal transplantation with regard to improving the long-term graft survival.

Technology evaluation: TG-1031, Transgene SA.

Tumor-associated antigens have considerable promise not only as diagnostic or prognostic markers but also as targets for active or passive immunotherapy. The epithelial mucin MUC1 is a transmembrane molecule which is expressed by most glandular epithelial cells. Transgene has developed VV-MUC1-IL-2 (TG-1031), an antigen-specific therapy, involving the tumor antigen MUC1 and the cytokine IL-2 combined with a vaccinia virus vector. Vaccinia virus vectors have been shown to stimulate a strong immune response to encoded antigens in vivo. This therapy has potential for the treatment of breast cancer, prostate cancer and other adenocarcinomas and is currently under investigation in phase I and II trials.