Plasmakonzentrationen von E-Cadherin bei Tumorerkrankungen der Harnblase

Background

Urinary bladder cancer represents a heterogeneous group of cancers regarding their clinical behaviour. For patients with muscle-invasive bladder cancer the 5-year disease-specific survival rate is only 50%. The main cause of death in this patient group is rapid metastatic progression following surgery. Clinicopathological features provide only limited information to predict disease progression in these patients. E-cadherin is a transmembrane glycoprotein critically involved in epithelial cell adhesion. Elevated circulating E-cadherin levels were shown to be correlated with progression of bladder cancer.

Material and methods

Plasma E-cadherin levels of 97 patients and 17 controls were analysed using an enzyme-linked immunosorbent assay, and results were compared with the clinical follow-up data.

Results

Plasma E-cadherin concentrations were significantly higher in patients than in controls (p<0.001). E-cadherin levels were not significantly correlated with clinicopathological parameters such as tumour stage (p=0.196), grade (p=0.570) and lymph node status (p=0.581). In a subgroup of patients treated by radical cystectomy, E-cadherin concentrations were higher in lymph node-positive cases; however, this correlation (p=0.100) failed to reach statistical significance. Furthermore, plasma E-cadherin levels were not able to predict disease-specific survival or metastasis-free survival (p=0.512 and p=0.197).

Conclusions

Our results suggest that soluble E-cadherin levels are not able to predict patients?? prognosis and underline the importance of external validation in prognostic marker research. Molecular markers predicting disease progression after radical cystectomy to identify high-risk patients and improve therapy decisions are still needed.     

The immunological phenotype of rituximab-sensitive chronic graft-versus-host disease: a phase II study

Chronic graft-versus-host disease is the major long-term complication after allogeneic stem cell transplantation with a suboptimal response rate to current treatments. Therefore, clinical efficacy and changes in lymphocyte subsets before and after rituximab treatment were evaluated in a prospective phase II study in patients with steroid-refractory chronic graft-versus-host disease. Overall response rate was 61%. Only responding patients were found to have increased B-cell numbers prior to treatment. B cells had a naïve-antigen-presenting phenotype and were mainly CD5 negative or had a low CD5 expression. Normal B-cell homeostasis was reestablished in responding patients one year after ritxumab treatment and associated with a significant decline in skin-infiltrating CD8⁺ T cells, suggesting that host B cells play a role in maintaining pathological CD8⁺ T-cell responses. Imbalances in B-cell homeostasis could be used to identify patients a priori with a higher chance of response to rituximab treatment (Eudra-CT 2008-004125-42).     

Mechanism-based pharmacokinetic-pharmacodynamic modelling of the reversal of buprenorphine-induced respiratory depression by naloxone : a study in healthy volunteers

BACKGROUND AND OBJECTIVE: Respiratory depression is a potentially life-threatening adverse effect of opioid therapy. It has been postulated that the difficulty of reversing buprenorphine-induced respiratory depression is caused by slow receptor association-dissociation kinetics at the opioid mu receptor. The aim of this study was to characterise the pharmacodynamic interaction between buprenorphine and naloxone in healthy volunteers. METHODS: A competitive pharmacodynamic interaction model was proposed to describe and predict the time course of naloxone-induced reversal of respiratory depression. The model was identified using data from an adaptive naloxone dose-selection trial following intravenous administration of buprenorphine 0.2mg/70kg or 0.4mg/70kg. RESULTS: The pharmacokinetics of naloxone and buprenorphine were best described by a two-compartment model and a three-compartment model, respectively. A combined biophase equilibration-receptor association-dissociation pharmacodynamic model described the competitive interaction between buprenorphine and naloxone at the opioid mu receptor. For buprenorphine, the values of the rate constants of receptor association (k(on)) and dissociation (k(off)) were 0.203 mL/ng/min and 0.0172 min(-)(1), respectively. The value of the equilibrium dissociation constant (K(D)) was 0.18 nmol/L. The half-life (t((1/2))) of biophase equilibration was 173 minutes. These estimates of the pharmacodynamic parameters are similar to values obtained in the absence of naloxone co-administration. For naloxone, the half-life of biophase distribution was 6.5 minutes. CONCLUSIONS: Because of the slow receptor association-dissociation kinetics of buprenorphine in combination with the fast elimination kinetics of naloxone, naloxone is best administered as a continuous infusion for reversal of buprenorphine-induced respiratory depression.     

Harnwegstumorregister

Ohne Zusammenfassung     

Induktive Systemtherapie mit kurativer Zielsetzung urologischer Tumoren

Up to now systemic therapy with curative intent is possible in only a few tumors. Concerning advanced malignant tumors in urology only testicular cancer can be cured. In metastatic urothelial cancer of the bladder this might be possible in single cases. In advanced renal cell carcinoma a recent group of new substances, so-called target-specific substances, have gained attention. In several phase III studies with sunitinib, sorafenib, and temsirolimus at least progression-free survival could be clearly prolonged. The amazing results in testicular cancer were possible by consistent performance of clinical trials. The success in treatment also is an example for interdisciplinarity. Especially in advanced stages treatment consists of two components, chemotherapy, correctly performed concerning dose and interval, followed by complete residual tumor resection.     

Identifikation der molekularen Grundlagen der Metastasierung zur Entwicklung neuer Therapiestrategien des metastasierten Prostatakarzinoms

Ohne Zusammenfassung     

Freie Hauttransplantate als Alternative bei plastisch rekonstruktiven Eingriffen am Genitale

Problem

In the field of plastic/reconstructive urology, surgery often concerns the correction of congenital anomalies. Besides anomalies of the upper urinary tract these are disorders of the external genitalia like hypospadias and more seldom epispadias or a buried penis in males as well as complete vaginal aplasia or nondevelopment of the distal part of the vagina in different forms of disorders of sexual differentiation in females. The use of local tissue is the first choice for reconstruction. However, there is not always enough local tissue or it has already been used during unsuccessful interventions before. In these cases the use of a free skin graft should be considered.

Patients and methods

We describe the cases of nine patients in whom a free skin graft was used for reconstruction. Two male patients had surgery because of a buried penis, and the third male patient underwent another revision after several unsuccessful corrections of epispadias. In two female patients with adrenogenital syndrome (AGS) construction of the distal vagina was necessary. Four patients had vaginal aplasia and needed a complete neovagina. In the male patients the free skin graft was harvested from the scrotum and in the female patients from the lower abdominal wall.

Results

In all nine patients the free skin graft is revascularized. The male patients show a good cosmetic result. The penile skin is mobile, which is also reflected by an unproblematic erection in the adult patient. The only complication in the female patients was a scar between the free skin graft and the skin of the proximal vagina in a patient with AGS. This scar was incised at 5 and 7 o’clock.

Conclusion

A free skin graft offers the possibility of effectively covering areas when there is insufficient local tissue.     

Patient perspectives on consequences of resection for colorectal cancer: A qualitative study

Background

Colorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal cancer. As treatment options tend to grow, more information on the effects of these treatments is needed to engage in shared decision-making. This study aims to explore the impact of resection for colorectal cancer on patients' daily life.

Methods

Patients (≥18 years of age) who underwent an oncological colorectal resection between 2018 and 2021 were selected. Purposeful sampling was used to include patients who differed in age, comorbidity conditions, types of (neo)adjuvant therapy, postoperative complications and the presence/absence of a stoma. Semi-structured interviews were conducted, guided by a topic guide. Interviews were fully transcribed and subsequently thematically analysed using the framework approach. Analyses were carried out using the following predefined themes: (1) daily life and activities; (2) psychological functioning; (3) social functioning; (4) sexual functioning; and (5) healthcare experiences.

Results

Sixteen patients with a follow-up period of between 0.6 and 4.4 years after surgery were included in this study. Participants reported several challenges experienced because of poor bowel function, a stoma, chemotherapy-induced neuropathy, fear of recurrence and sexual dysfunction. However, they reported these as not interfering much with daily life.

Conclusion

Colorectal cancer treatment leads to several challenges and treatment-related health deficits. This is often not recognized by generic patient-reported outcome measures, but the findings on treatment-related health deficits presented in this study contain valuable insights which might contribute to improving colorectal cancer care, shared decision making and value-based health care.