Insulin-like growth factor-1 (IGF-1)-related signaling is associated with prostate cancer progression. Links were explored between IGF-1 and expression of integrin adhesion receptors to evaluate relevance for growth and migration. Androgen-resistant PC3 and DU145 and androgen-sensitive LNCaP and VCaP prostate cancer cells were stimulated with IGF-1 and tumor growth (all cell lines), adhesion and chemotaxis (PC3, DU145) were determined. Evaluation of Akt/mTOR-related proteins, focal adhesion kinase (FAK) and integrin α and β subtype expression followed. Akt knock-down was used to investigate its influence on integrin expression, while FAK blockade served to evaluate its influence on mTOR signaling. Integrin knock-down served to investigate its influence on tumor growth and chemotaxis. Stimulation with IGF-1 activated growth in PC3, DU145, and VCaP cells, and altered adhesion and chemotactic properties of DU145 and PC3 cells. This was associated with time-dependent alterations of the integrins α3, α5, αV, and β1, FAK phosphorylation and Akt/mTOR signaling. Integrin blockade or integrin knock-down in DU145 and PC3 cells altered tumor growth, adhesion, and chemotaxis. Akt knock-down (DU145 cells) cancelled the effect of IGF-1 on α3, α5, and αV integrins, whereas FAK blockade cancelled the effect of IGF-1 on mTOR signaling (DU145 cells). Prostate cancer growth and invasion are thus controlled by a fine-tuned network between IGF-1 driven integrin-FAK signaling and the Akt-mTOR pathway. Concerted targeting of integrin subtypes along with Akt-mTOR signaling could, therefore, open options to prevent progressive dissemination of prostate cancer.

Background: To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes. Methods: Using the Surveillance, Epidemiology, and End Results database (2004–2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models. Results: Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients. Conclusions: Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.

Background: In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown. Patients and Methods: Relying on the National Inpatient Sample (2000–2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes. Results: Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5). Conclusions: History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality.

Zusammenfassung Hintergrund Die Zeit der ärztlichen Weiterbildung markiert den Karrierebeginn junger Urolog:innen und ist damit ein Grundstein für die zukünftige Krankenversorgung. 2015 führte die German Society of Residents in Urology e. V. (GeSRU) erstmals eine Befragung unter den Ärzt:innen in urologischer Weiterbildung durch und beschrieb den Status quo deren Weiterbildung. Mit dieser Folgeuntersuchung soll ein aktualisiertes Abbild der Weiterbildungs- und Arbeitsbedingungen junger Urolog:innen erstellt und eine Verlaufsbeurteilung ermöglicht werden. Methoden Die GeSRU führte 2020 eine onlinebasierte Befragung aller Ärzt:innen in urologischer Weiterbildung durch. Dafür wurde der Fragebogen von 2015 ausgebaut. Es wurde erneut das Modell der beruflichen Gratifikationskrise eingesetzt. Ergebnisse Insgesamt wurden 332 Fragebögen ausgewertet. Im Vergleich zu 2015 ergaben sich keine wesentlichen Änderungen. Der Arbeitsalltag stellt sich weiterhin stark verdichtet dar. Zudem ist der Einfluss ökonomischer Erwägungen auf die Teilnehmenden weiterhin deutlich spürbar. Familien- und forschungsfreundliche Arbeitsbedingungen fehlen weitgehend. 35 % der Befragten ziehen hieraus berufliche Konsequenzen. Die psychosoziale Belastung ist sehr hoch und stellt ein Risiko für die Gesundheit der Ärzt:innen selbst sowie für die Behandlungsqualität ihrer Patient:innen dar. Schlussfolgerung Auf Basis dieser Befragung bestehen weiterhin systemrelevante Belastungen im Arbeitsleben junger Ärzt:innen in urologischer Weiterbildung, die Anpassungen der Arbeits- und Weiterbildungsbedingungen erfordern. Ein strukturiertes, transparentes Weiterbildungscurriculum, Vergütung von und Zeit für gute Weiterbildung und Modelle zur Vereinbarkeit von Forschung bzw. Familie und Beruf sollten etabliert werden.

To assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement. Using the National Inpatient Sample (2000-2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes. Of 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62-2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality. Radical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality.