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PSMA-PET/CT for imaging prostate cancer (PC) has spread worldwide since its clinical introduction in 2011. The majority of experiences have been collected for PSMA-PET-imaging of recurrent PC. Data for primary staging of high-risk PC are highly promising. Meanwhile, a plethora of PSMA-ligands are available for clinical use (e.g. 68Ga-PSMA-11, 68GaPSMA-I&T, 68Ga-PSMA-617, 18F-DCFBC, 18F-DCFPyL, 18F-PSMA-1007, 18F-rhPSMA-7 and 18F-JK-PSMA-7). However, an official approval is available only for 68Ga-PSMA-11 (approved by the US FDA in 2020) and 18F-DCFPyL (approved by the US FDA in 2021). Recommendations for acquisition times vary from 1-2h p.i. It has been shown that for the majority of tumour lesions, the contrast in PSMAPET/CT increases with time. Therefore, additional late imaging can help to clarify unclear findings. PSMA-PET/CT should be performed prior to commencing an androgen deprivation therapy (ADT) since (long term) ADT reduces the visibility of PC lesions. Following injection of PSMA-ligands, hydration and forced diuresis are recommended for PSMA-ligands with primarily excretion via the kidneys in order to increase the visibility of tumour lesions adjacent to the urinary bladder. PSMA-ligands are physiologically taken up in multiple normal organs. For some 18F-labelled PSMA-ligands, presence of unspecific focal bone uptake has been reported. When using these tracers, focal bone uptake without CT-correlate should be interpreted with great caution. Besides prostate cancer, practically all solid tumors express PSMA in their neovasculature thereby taking up PSMA-ligands, although usually at a lower extent compared to PC. Also multiple benign lesions and inflammatory processes (e.g. lymph nodes) take up PSMA-ligands, also usually at lower extent compared to PC.

Das Ziel der vorliegenden Leitlinie ist es, den Arzt bei der Indikationsstellung, der standardisierten Durchführung, der Interpretation und der Dokumentation der Befunde einer Positronen-Emissions-Tomographie/Computertomographie (PET/CT) mit PSMA-Liganden bei Patienten mit Prostatakarzi-nom zu unterstützen. Es werden Empfehlungen zu Patientenselektion, Bilderfassung, Interpretati-on und Befundung ausgesprochen sowieLimitationen der PSMA-Liganden-PET/CT präsentiert. Die Leitlinie basiert auf einer Zusammenführung wissenschaftlicher Veröffentlichungen, Empfehlungen der Autoren und evidenzbasierter Daten.

Introduction: A surgeon is constantly faced with the question to preserve the kidneys and their function for diverse lesions of the ureter. Often these lesions limit the kidneys in their performance. Material and methods: Between 2001 and 2015, five renal auto transplantations were performed at our center. The patients’ demographic, clinical and lab data was collected and analysed in the pre, intra, and postoperative phases. Results: All five patients in our center undergoing surgery because of ureteral lesions. The retention results were when compared preoperatively to the date of discharge stable. Conclusion: With the data we collected in this study we can only confirm the good long-term results after kidney auto transplantation with stable kidney function. Following the corresponding indication, kidney auto transplantation is a safe and effective procedure to retain the kidney’s function.

To report a large multi-institutional series of laparoendoscopic single-site (LESS) nephroureterectomy (NU).Data on all cases of LESS-NU performed between 2008 and 2012 at 15 institutions were retrospectively gathered. The main demographic data and perioperative outcomes were analysed.The study included 101 patients whose mean (SD) age was 66.4 (9.9) years and mean (SD) body mass index was 24.8 (4) kg/m², and of whom 29.7% had undergone previous abdominal/pelvic surgery. The mean (SD) operating time was 221.4 (73.7) min, estimated blood loss 231.7 (348.0) mL. A robot-assisted LESS technique was applied in 25.7% of cases. An extra trocar was inserted in 28.7% of cases to complete the procedure. Conversion to open surgery was necessary in three cases (3.0%). There was no bladder cuff excision in 20.8% of cases, and excision was carried out using a variety of techniques in the remaining cases. Six intra-operative complications occurred (5.9%). The mean (SD) length of hospital stay was 6.3 (3.5) days. The overall postoperative complication rate was 10.0%, and most of the complications were low grade (Clavien grades 1 and 2). The mean tumour size was 3.1 (1.9) cm. Pathological staging was pTis in two patients, pTa in 12 patients, pT1 in 42 patients, pT2 in 20 patients, pT3 in 23 patients and pT4 in two patients. Pathological grade was high in 71 and low in 30 patients. At a mean follow-up of 14 months, six patients (5.9%) had died. Disease recurrence (including distant and bladder recurrence) was detected in 22.8% of patients, with a mean time to recurrence of 11.5 months.This study reports the largest multi-institutional experience of LESS-NU to date. Peri-operative outcomes mirror those of published standard laparoscopy series. Despite encouraging early findings, longer follow-up is needed to determine the oncological efficacy of the procedure.

To evaluate the safety and feasibility of laparoscopic adrenalectomy (LA) performed in several German centres with different laparoscopic experience, as LA has become the gold-standard approach for benign surgical adrenal disorders; however, for solitary metastasis or primary adrenal cancer its precise role is uncertain.The data of 363 patients who underwent a LA were prospectively collected in 23 centres. All centres were stratified into three groups according to their experience: group A (10 LAs/year), group B (10-20 LAs/year) and group C (20 LAs/year). In all, 15 centres used a transperitoneal approach, four a retroperitoneal approach and four both approaches. Demographic data, perioperative and postoperative variables, including operating time, surgical approach, tumour size, estimated blood loss, complications, hospital stay and histological tumour staging, were collected and analysed.The transperitoneal approach was used in 281 cases (77.4%) and the retroperitoneal approach was used in 82 patients (22.6%). In all, 263 of 363 lesions (72.5%) were benign and 100 (27.5%) were malignant. The mean (sd) operating time was 127.22 (55.56) min and 130.16 (49.88) min after transperitoneal and retroperitoneal LA, respectively. The mean complication rates for transperitoneal and retroperitoneal LA were 5% and 10.9%, respectively.LAs performed by urologists experienced in laparoscopy is safe for the removal of benign and malignant adrenal masses. LA for malignant adrenal tumours should be performed only in high-volume centres by a surgeon performing at least10 LAs/year.

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

To investigate the outcome of ICSI cycles, using frozen-thawed testicular spermatozoa from patients suffering from non-obstructive azoospermia, in relation to the spouse's response to ovarian stimulation.A retrospective study with two groups of couples where males suffered from non-obstructive azoospermia. In group 1 (n = 14), the female partners responded poorly to ovarian stimulation (or = 4 oocytes retrieved). In group 2 (n=14), the female partners responded well (or = 10 oocytes retrieved). Both groups underwent 14 cycles of ICSI using frozen-thawed spermatozoa obtained by TESE.The total amount of gonadotropin, the duration of stimulation, the peak estradiol concentrations and the number of oocytes were significantly different between the two groups. Despite the satisfactory fertilisation rates, the outcome in poor responders was disappointing due to a low number of oocytes. There was only one pregnancy in the poor responder group whereas there were four in the group that responded well. The pregnancy rates per oocyte collection were 7.14% in group 1 versus 28.57% in group 2. The implantation rates were 60.60% versus 55.33%, respectively.It is possible to achieve satisfactory fertilisation rates using frozen-thawed, surgically-retrieved testicular spermatozoa, but the poor ovarian response to stimulation induction is the limiting factor in reaching implantation and pregnancy. It is preferable that poorly stimulated cycles be canceled, in the hope of a better subsequent response.

To compare the outcome of intracytoplasmic sperm injection (ICSI) cycles performed with frozen-thawed epididymal spermatozoa between patients who respond poorly and patients who respond well to ovarian stimulation.17 patients suffering from obstructive azoospermia underwent microsurgical retrieval of epididymal spermatozoa (MESA) and the spermatozoa were frozen. The frozen-thawed spermatozoa were used in subsequent ICSI cycles. In six patients, the female partners responded poorly to ovarian stimulation. They accomplished nine ICSI cycles. In 11 patients, the female partners responded well to ovarian stimulation and they accomplished 16 cycles.Poor responders were older than those who reponded well. The mean number of metaphase II oocytes collected was lower in the poor responder group. In the poor responders, two couples failed to fertilise the oocytes in two ICSI cycles. In the good responders, one couple failed to fertilise the oocytes in an ICSI cycle. There were no significant differences in fertilization rates between the two groups. The estradiol concentrations on the day of hCG administration were significantly higher in the good responders. There was no pregnancy in the poor responder group, while three patients who responded well conceived. Eight good responders had 34 supernumerary 2PN oocytes which were cryopreserved.Frozen-thawed epididymal spermatozoa from men with obstructive azoospermia are potent to achieve satisfactory fertilization rates. Poor ovarian response to stimulation induction appears to be the main limiting factor in reaching the stage of embryo transfer. It is preferable in older women to cancel cycles with poor response in the hope that a better response might be obtained in a subsequent cycle. Thus, the frozen-thawed epididymal sperm can be preserved and the most stressful and expensive phase of IVF-ICSI treatment can be avoided.

Prosthetic substitution of the glenohumeral joint, begun at the end of the last century, has developed greatly in recent years. Today the most widely used shoulder prostheses are defined as "modular" because of their extensive adaptability. The capacity to adapt to anatomic variations must be incorporated within their structure, and normal articular biomechanics must be respected. The choice of prosthesis must be based on the condition of the joint surfaces, on the anatomic and functional condition of the rotator cuff. So endoprosthesis of the shoulder is indicated for avascular necrosis of the head of the humerus, fractures and pseudoarthrosis of the extreme proximal end of the humerus, arthropathy following rotator cuff rupture. Total shoulder prosthetization is indicated for glenohumeral osteoarthritis, rheumatoid arthritis and outcomes of endoprosthesis. The principal contraindications for shoulder replacement include an infection in progress, Charcot's arthropathy and severe neurological pathologies. The complications of shoulder prostheses include infection, dislocation, loosening of a component, periprosthetic humeral and glenoid fractures, nerve injuries, fractures of a prosthetic component and ectopic ossification. At present prosthetic substitution of the glenohumeral joint offers good results. Indispensable conditions for these results include anatomic and functional integrity of the musculature, good bone quality, correct positioning of the prosthetic components and a proper rehabilitation program.

Laparoscopic Nephron Sparing Surgery (LNSS) is a technically challenging procedure. Technical aspects and the outcome of LNSS are investigated. A total of 592 LNSS procedures were collected from 12 Centres, either in extraperitoneal or transperitoneal fashion. Mean tumor size was 2.2 cm. Eight centers reported on tumor position for a total of 407 cases with 338 exophytic tumors (83%) and 69 deep lesions (17%). Four centers, accounting for 185 cases, did not report on tumor position. All the centers performed their LNSS by clamping the hilum. The warm ischemia time was < 30 min in all the centers. The positive margin rate was 2% (12/592). Hemostatic agents and/or sealant or tissue glues were used in 86% of cases (511/592). Types of sealants used included: gelatine matrix (Floseal), fibrin gel (Tissucol), bovine serum albumin (BioGlue) and cianacrylate (Glubran). Two Centres never used sealants, one center used only sealants without suturing and 9 centers used a combination of sealants and bolstering-sutures. The intraoperative open conversion rate was 3.5% (21/592). Postoperative complications included bleeding in 15/592 (2.5%) and urine leak in 13/592 (2.1%). No tumor seeding was reported. LNSS has similar results of open partial nephrectomy. The use of hemostatic agents and/or sealants or tissue glues during LNSS is largely diffuse in European centers and may be an effective add on reducing bleeding and urine leakage when used in combination with bolstering-suturing

OBJECTIVES: Background. Nephron-sparing surgery (NSS) ensures excellent oncological and func'ional outcomes in treating small renal masses. Laparo-Endoscopic-Single-Site Surgery (LESS) is one of the major advances in the evolution of minimally invasive surgery METHODS: A prospective evaluation of patients underwent LESS NSS at our institutions for a solitary, exophytic, enhancing, small (

Background Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the surgical trauma associated with conventional laparoscopy. Partial nephrectomy (PN) represents a challenging indication for LESS. Objective To report a large multi-institutional series of LESS-PN and to analyze the predictors of outcomes after LESS-PN. Design, setting, and participants Consecutive cases of LESS-PN done between November 2007 and March 2012 at 11 participating institutions were included in this retrospective analysis. Intervention Each group performed LESS-PN according to its own protocols, entry criteria, and techniques. Outcome measurements and statistical analysis Demographic data, main perioperative outcome parameters, and perioperative complications were gathered and analyzed. A multivariable analysis was used to assess the factors predicting a short (≤20min) warm ischemia time (WIT), the occurrence of postoperative complication of any grade, and a favorable outcome , arbitrarily defined as a combination of the following events: short WIT plus no perioperative complications plus negative surgical margins plus no conversion to open surgery or standard laparoscopy. Results and limitations A total of 190 cases were included in this analysis. Mean renal tumor size was 2.6, and PADUA score 7.2. Median operative time was 170min, with median estimated blood loss (EBL) of 150ml. A clampless technique was adopted in 70 cases (36.8%), and the median WIT was 16.5min. PADUA score independently predicted length of WIT (low vs high score: odds ratio [OR]: 5.11 [95% confidence interval (CI), 1.50–17.41]; p =0.009; intermediate vs high score: OR: 5.13 [95% CI, 1.56–16.88]; p =0.007). The overall postoperative complication rate was 14.7%. The adoption of a robotic LESS technique versus conventional LESS (OR: 20.92 [95% CI, 2.66–164.64]; p =0.003) and the occurrence of lower (≤250ml) EBL (OR: 3.60 [95% CI, 1.35–9.56]; p =0.010) were found to be independent predictors of no postoperative complications of any grade. A favorable outcome was obtained in 83 cases (43.68%). On multivariate analysis, the only predictive factor of a favorable outcome was the PADUA score (low vs high score: OR: 4.99 [95% CI, 1.98–12.59]; p Conclusions LESS-PN can be safely and effectively performed by experienced hands, given a high likelihood of a single additional port. Anatomic tumor characteristics as determined by the PADUA score are independent predictors of a favorable surgical outcome. Thus patients presenting tumors with low PADUA scores represent the best candidates for LESS-PN. The application of a robotic platform is likely to reduce the overall risk of postoperative complications.

We analyzed the incidence of and risk factors for complications and conversions in a large contemporary series of patients treated with urological laparoendoscopic single site surgery.The study cohort consisted of consecutive patients treated with laparoendoscopic single site surgery between August 2007 and December 2010 at a total of 21 institutions. A logistic regression model was used to analyze the risks of conversion, and of any grade and only high grade postoperative complications.Included in analysis were 1,163 cases. Intraoperatively complications occurred in 3.3% of cases. The overall conversion rate was 19.6% with 14.6%, 4% and 1.1% of procedures converted to reduced port laparoscopy, conventional laparoscopic/robotic surgery and open surgery, respectively. On multivariable analysis the factors significantly associated with the risk of conversion were oncological surgical indication (p=0.02), pelvic surgery (p0.001), robotic approach (p0.001), high difficulty score (p=0.004), extended operative time (p=0.03) and an intraoperative complication (p=0.001). A total of 120 postoperative complications occurred in 109 patients (9.4%) with major complications in only 2.4% of the entire cohort. Reconstructive procedure (p=0.03), high difficulty score (p=0.002) and extended operative time (p=0.02) predicted high grade complications.Urological laparoendoscopic single site surgery can be done with a low complication rate, resembling that in laparoscopic series. The conversion rate suggests that early adopters of the technique have adhered to the principles of careful patient selection and safety. Besides facilitating future comparisons across institutions, this analysis can be useful to counsel patients on the current risks of urological laparoendoscopic single site surgery.

A 66-yr-old man with pain and swelling in the right flank was referred to our clinic for diagnosis. In 2005, the patient underwent a laparoscopic partial nephrectomy for renal cancer of the lower pole of the right kidney. A computed tomography scan revealed a 20-cm tumor in the right abdominal wall, resulting in a suspected diagnosis of port-site metastasis from the first laparoscopic operation. The patient underwent open surgery, which confirmed the diagnosis. After the operation, the patient recovered rapidly.

Die Zytokine Interleukin-2 und Interferon-a2a nehmen eine zentrale Stellung bei der Behandlung von Patienten mit metastasierten Nierenzellkarzinomen ein. Im klinischen Teil der Arbeit wurde die Effektivität der Chemoimmuntherapie monozentrisch an 107 Patienten untersucht. Es zeigte sich eine Rate objektiver Remissionen von 22 % (95 % CI 14,6 - 31,3 %) mit einer zusätzlichen Rate an vorübergehenden Stabilisierungen von 46 %. Das mediane Überleben lag bei 19 Monaten mit einer kalkulierten 5-Jahres-Überlebensrate von 17 %. In der multivariaten Analyse zeigte sich eine hochsignifikante Abhängigkeit vom Karnofsky-Performance-Index der Patienten. Bei den 83 Patienten mit einem Karnofsky-Performance-Index von über 80 % lag das mediane Überleben bei 23 Monaten mit einer kalkulierten 5-Jahres-Überlebensrate von 21 %. Diese Untersuchungsergebnisse rechtfertigen eine weitere Prüfung der Kombination von Interleukin-2, Interferon-a2a und 5-Fluorourazil im Rahmen prospektiver klinischer Studien. In Weiterentwicklung der klinischen Aspekte zur Zytokin-basierten Immuntherapie war es die Aufgabenstellung des experimentellen Teils dieser Arbeit, die Bedeutung von 70 kDa Hitzeschockproteinen (HSP70) beim Nierenzellkarzinom zu untersuchen. Neben ihrer Funktion im Rahmen der zellulären Stressverarbeitung haben Mitglieder der HSP70-Familie (HSP72 und HSP73) eine außerordentliche Bedeutung für tumorimmunologische Fragestellungen erlangt, die sich aus der immunologischen Signalfunktion, der HSP72-vermittelten Interaktion von immunologischen Effektorzellen und Tumorzellen und der Beteiligung von HSP70 an der Peptidprozessierung in malignen Zellen ergeben. An einer Nierenkarzinomzelllinie und an Primärzellen von Nierenkarzinomen konnte die HSP72-Oberfächenexpression durchflusszytometrisch auf der Tumorzelloberfläche nachgewiesen und an der Zelllinie mit einer erhöhten Lyse der Tumorzellen durch Interleukin-2 stimulierte NK-Zellen korreliert werden. Im Gegensatz zu bisherigen Literaturbefunden zeigte sich in diesem Modell jedoch, dass die Membranexpression von HSP72 nicht nur auf maligne Zellen beschränkt, sondern auch bei renalen Zellen aus Normalgewebe nachzuweisen war. In einer immunhistochemischen Studie zur basalen, zytoplasmatischen HSP72-Expression zeigte sich univariat eine signifikante Korrelation einer hohen HSP72-Expression und dem Überleben der Patienten. In einer multivariaten Analyse konnte das Ausmaß der HSP72-Expression als unabhängiger prognostischer Parameter identifiziert werden, der auch mit dem Ansprechen auf eine Chemoimmuntherapie korreliert. Die klinische Etablierung spezifisch wirksamer Vakzinen nimmt eine zentrale Rolle bei der Entwicklung neuer Behandlungsmethoden des metastasierten Nierenzellkarzinoms ein. Dabei spielen Vakzinen auf der Basis von HSP-Peptid-Vakzinen eine besondere Rolle. Ein weiterer Bestandteil der experimentellen Arbeiten war daher in der Entwicklung einer Methode zur Aufreinigung von HSP70-Peptid-Komplexen. Mit der ADP-Affinitätschromatographie konnte eine Methode zur Anwendung gebracht und patentiert werden, durch die sich HSP70-Peptid-Komplexe aus Tumorzellen anreichern lassen. Die HSP70-Peptid-Komplexe sind einerseits für HSP-basierte Vakzinekonzepte verfügbar oder können andererseits für die Identifikation und Charakterisierung HSP70-gebundenener biologisch-aktiver (immunogener) Peptide genutzt werden. Die vorliegenden Untersuchungsergebnisse demonstrieren, dass HSP72 per se eine prognostische Bedeutung beim Nierenzellkarzinom besitzt und weisen auf die potentielle Bedeutung von HSP72 als immunologische Zielstruktur hin. Die Resultate stellen neue Ansätze zum tieferen Verständnis der immunogenen Eigenschaften des Nierenzellkarzinoms dar und liefern Ausgangspunkte für die Etablierung innovativer Vakzinationskonzepte bei der Behandlung des fortgeschrittenen Nierenzellkarzinoms., The cytokines interleukin-2 and interferon-a2a are of central importance in the treatment of patients with metastatic renal cell cancer. In the clinical part of the thesis the efficacy of chemoimmunotherapy was investigated monocentrically on 107 patients. It appeared a rate of objective remissions of 22% (95% CI 14.6 - 31.3%) and an additional rate of temporary disease stabilisations of 46%. The median survival was 19 months, with a calculated 5-year survival rate of 17%. Multivariate analysis revealed a highly significant dependence on the Karnofsky-Performance-Index of the patients. In 83 patients with Karnofsky-Performance-Index over 80% the median survival was 23 months, with a calculated 5-year survival of 21%. These results justify the further investigation of the combination of interleukin-2, interferon-a2a, and 5-fluorouracil in prospective clinical studies. In the context of the clinical aspects of cytokine-based immunotherapy it was the task of the the experimental part of the study to investigate the importance of 70 kDa heat shock proteins (HSP70) in renal cell cancer. Besides their function in cellular stress processing, members of the HSP70 family (HSP72 and HSP73) are especially important for answering questions of tumor immunology resulting from their immunological signal function, the HSP72-mediated interaction of immunological effector cells with tumor cells, and from the involvement of HSP70 in peptide processing in malignant cells. On the basis of a renal cancer cell line and of primary cells of renal carcinomas the HSP72 expression on the surface of tumor cells could be demonstrated by flow cytometry and correlated with an increased lysis of tumor cells on the cell line by interleukin-2 stimulated natural killer cells. In contrast to the findings so far reported in the literature, the present model revealed that the membrane expression of HSP72 was not limited to malignant cells but was detectable in renal cells of normal tissue too. In an immunohistochemical study on basal cytoplasmatical HSP72 expression, a univariate analysis showed a significant correlation of high HSP72 expression and patient survival. In a multivariate analysis the extent of the HSP72 expression could be identified as an independent prognostic parameter that was also correlated with the response of patients to chemoimmunotherapy. The clinical establishment of specifically effective vaccines plays a central part in the development of new treatment strategies for metastatic renal cell cancer. In this context, vaccines on the basis of HSP-peptides are of special interest. Therefore, the experimental part of the work was also aimed at developing a method for enriching HSP70-peptide complexes. With ADP affinity chromatography a method for concentrating HSP70-peptide complexes from tumor cells was created, which proved to be usable and was patented. On the one hand, HSP70-peptide complexes can be used for HSP-based vaccine programmes, on the other hand, they can serve for identifying and characterizing HSP70-bound biologically active (immunogenic) peptides. The present findings demonstrate that HSP72 per se has a prognostic value in renal cell cancer and point to the potential importance of HSP72 as an immunological target structure. The results represent new approaches to a deeper understanding of the immunological properties of renal cell carcinoma and give a basis from which to establish innovative vaccination programmes for the treatment of advanced renal cell carcinoma.