The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.

1,3-Halogen migration as an entry to aryl coppers from an unintuitive starting material.

A copper(I) catalyzed 1,3-halogen migration/borylation migrates a bromine from an sp(2) carbon to a benzylic carbon with concomitant borylation of the aryl-bromine bond. This transformation proceeds via an aryl copper intermediate which can be accessed independently and then trapped with electrophiles. As such, copper-catalyzed 1,3-halogen migration provides unique and mild access to an aryl copper species that allows for rapid aromatic functionalization from an unconventional starting material.

[Value of immunotherapy in the perioperative treatment of localized muscle invasive bladder cancer]. / Stellenwert der Immuntherapie in der perioperativen Behandlung des lokalisierten muskelinvasiven Harnblasenkarzinoms.

Immune checkpoint inhibitors are standard of care in the treatment of metastatic and locally advanced urothelial cancer. Their use in perioperative treatment is currently under investigation as monotherapy as well as in combination with chemotherapy or radiation regimens. This article provides an overview of recent trials, current data as well as an outlook on future developments in the perioperative management of urothelial cancer.

["Surgery only" is not enough: potential of multimodal therapy in urothelial bladder carcinoma]. / "Surgery only" reicht nicht aus: Potenziale einer multimodalen Therapie beim Urothelkarzinom der Harnblase.

Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Using perioperative cisplatin-based chemotherapy, 5­year overall survival rates are 5% higher with neoadjuvant chemotherapy compared to local therapy alone. New multimodal concepts have been developed to improve oncologic efficacy and to reduce treatment-related morbidity. Perioperative use of checkpoint inhibitors aims at improving efficacy, while bladder-preserving concepts try to avoid cystectomy in good responders. This article reviews new developments in radioimmunotherapy and perioperative combination therapies as well as bladder-preserving concepts like trimodal bladder therapy.

[Immuno-oncological approaches in the perioperative therapy of muscle invasive bladder cancer]. / Immunonkologische Ansätze in der perioperativen Therapie des muskelinvasiven Urothelkarzinoms.

Perioperative chemotherapy has become a standard treatment for muscle invasive bladder cancer and is recommended by national and international guidelines. The treatment of metastatic urothelial cancer evolved by the use of immune-modulating therapies like checkpoint inhibitors. Many clinical trials have been initiated which try to evaluate the role of immune checkpoint inhibition in the neoadjuvant and adjuvant setting. These trials focus not only on monotherapy, but also on the combination of checkpoint inhibitors with classical chemotherapy or with local radiation therapy (radioimmunotherapy). In neoadjuvant radioimmunotherapy, the radiation is supposed to act as a sensitizer for the systemic effects of checkpoint inhibition, in addition to the local effects. This review presents and discusses current trials and published results for perioperative immunomodulating treatment-alone or in combination-in muscle invasive bladder cancer.

[Update 2016 - Immunotherapy for urothelial carcinoma]. / Update 2016 - Immuntherapie beim Urothelkarzinom.

Advanced urothelial carcinoma of the bladder is an aggressive tumor with a poor prognosis. Besides surgical therapy, classical chemotherapy with platinum compounds is the mainstay of advanced bladder cancer treatment. In recent years, immune modulating therapies have come into the focus of clinical trials. This review provides an overview of the biological mechanisms and immuno-oncological drugs that are currently being analyzed in clinical trials as well as established standard therapies.

[Pharmaceutical treatment of advanced urinary bladder cancer: new developments in 2014]. / Medikamentöse Therapie des fortgeschrittenen Blasenkarzinoms : Neue Entwicklungen 2014.

The perioperative treatment of muscle-invasive bladder cancer has become a standard procedure in recent years. New agents, such as programmed cell death protein 1 (PD1) and PD1-ligand 1 (PD1-L1) inhibitors have opened up the door for immunomodulation therapy of metastasized bladder cancer. This article focuses on data which have changed or have the potential to change the pharmaceutical treatment of advanced bladder cancer with a review of the literature in Medline PubMed and proceedings of major meetings, e.g. the European Association of Urology (EAU), the American Society of Clinical Oncology (ASCO), the ASCO Genitourinary Cancers Symposium (ASCO GU) and the American Urological Association (AUA).

[Current developments in the medical treatment of advanced urothelial carcinoma of the bladder]. / Aktuelle Entwicklungen in der medikamentösen Therapie des fortgeschrittenen Blasenkarzinoms.

Medical treatment of advanced urothelial carcinoma of the bladder consists of perioperative treatments as well as palliative chemotherapy in advanced stages. This article focuses on important clinical trials and developments of the last two years, with a review of literature and proceedings of the relevant meetings (ASCO, GU-ASCO, EAU, AUA). The general benefit of perioperative chemotherapy is confirmed. Chemotherapy with Gemcitabin/Cisplatin remains the therapy of choice in the palliative setting. So far, targeted therapies did not show convincing results.

Formal Asymmetric Hydrobromination of Styrenes via Copper-Catalyzed 1,3-Halogen Migration.

An enantioselective Cu(I)-catalyzed 1,3-halogen migration reaction accomplishes a formal hydrobromination by transferring a bromine activating group from a sp2 carbon to a benzylic carbon in good er and with concomitant borylation of the Ar-Br bond. Computational modelling aids in understanding the reaction outcome and suggests future directions to improve the formal asymmetric hydrobromination. The benzyl bromide can be displaced with a variety of nucleophiles to produce a wide array of functionalized products.

[Hands-on teaching for students in urology: the use of peer teaching and simulators]. / Praktische Studentenausbildung in der Urologie: Einsatz von studentischen Tutoren und Simulatoren.

BACKGROUND: Hands-on training in urology for medical students is characterized by several challenges. We tried to improve our practical training day using peer teaching/peer-assisted learning and simulators. MATERIAL AND METHODS: An average of 116 students participated in our practical training day every semester between 2007/2008 and summer semester 2011. We evaluated students' satisfaction, human resources, and student to teacher ratio before and after the restructuring. RESULTS: After the restructuring in 2008/2009, all categories showed improvement (1=best; 6=worst). The general rating rose from 2.2 (2008) to 1.45 (2011); practical training improved from 2.85 (2008) to 1.55 (2011). DISCUSSION: Peer teaching and simulators are reasonable tools in medical education in urology. They increase individual coaching of students and lead to improved satisfaction and subjective learning success. Interprofessional education with the selective use of nursing staff as teachers was widely accepted. With these tools essential hands-on skills in urology can be acquired by all medical students.

[Systemic therapy of metastatic bladder cancer.] / Systemische Therapie des metastasierten Blasenkarzinoms.

This review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.