Selective Intra-arterial Chemotherapy with Floxuridine as Second- or Third-Line Approach in Patients with Unresectable Colorectal Liver Metastases

Background: An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). Methods: Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. Results: Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6months (range, 2.5-55.7months), 3.9months (range, 0.7-55.7months), and 5.5months (range, 1.6-55.7months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P=0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P=0.09). No differences were observed in OS (P=0.69) or PFS (P=0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P<0.0001). Toxicities were manageable with dose modifications and supportive measures. Conclusions: FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsize

Lack of Effective Anti-Apoptotic Activities Restricts Growth of Parachlamydiaceae in Insect Cells

The fundamental role of programmed cell death in host defense is highlighted by the multitude of anti-apoptotic strategies evolved by various microbes, including the well-known obligate intracellular bacterial pathogens Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. As inhibition of apoptosis is assumed to be essential for a successful infection of humans by these chlamydiae, we analyzed the anti-apoptotic capacity of close relatives that occur as symbionts of amoebae and might represent emerging pathogens. While Simkania negevensis was able to efficiently replicate within insect cells, which served as model for metazoan-derived host cells, the Parachlamydiaceae (Parachlamydia acanthamoebae and Protochlamydia amoebophila) displayed limited intracellular growth, yet these bacteria induced typical features of apoptotic cell death, including formation of apoptotic bodies, nuclear condensation, internucleosomal DNA fragmentation, and effector caspase activity. Induction of apoptosis was dependent on bacterial activity, but not bacterial de novo protein synthesis, and was detectable already at very early stages of infection. Experimental inhibition of host cell death greatly enhanced parachlamydial replication, suggesting that lack of potent anti-apoptotic activities in Parachlamydiaceae may represent an important factor compromising their ability to successfully infect non-protozoan hosts. These findings highlight the importance of the evolution of anti-apoptotic traits for the success of chlamydiae as pathogens of humans and animals

Molekular zielgerichtete Therapie

Until recently, cancer therapy was based on three modalities: surgery, radiotherapy, and cytostatic chemotherapy. In most instances treatment of solid tumors was a surgical domain. For patients with incomplete resection or relapse after surgery, radiotherapy and chemotherapy usually offered only partial response and mostly of limited duration. By the mid-1990s visions of antibody-based therapies, vaccination strategies, and even gene-specific therapies existed but seemed far from clinical practice. United States Federal Drug Administration approval of the humanized antibody rituximab (1997) and the tyrosine kinase inhibitor imatinib (2001) has changed perceptions of oncologic treatment. These drugs turned visions into reality and led the pharmaceutical industry, clinicians, and patients to new perspectives. This article gives an overview of the development of this fourth modality in cancer therapy, so-called targeted therapy

Effects of an outpatient physical exercise program on hematopoietic stem-cell transplantation recipients: a randomized clinical trial

Patients who undergo hematopoietic stem cell transplantation (HSCT) often experience physical and psychological problems, even long after treatment has been completed. This study was performed to evaluate the effects of a 12-week outpatient physical exercise program, incorporating aerobic and strength exercises, as compared to a usual care control condition on patients’ physical performance and psychosocial well-being. Methods: Patients who had completed HSCT up to 6 months earlier were randomly assigned to a supervised physical exercise program (n = 64) or a usual care control group (n = 67). Primary outcomes were quantified physical performance and self-reported physical functioning. Secondary outcomes were body composition measurement, quantified walking activity and patient-reported outcomes (physical activity, fatigue and health-related quality of life). Assessments were at baseline, immediately after program completion and at 3-month follow-up. Results: Significant intervention effects were observed at both post-treatment and follow-up on physical performance measures. No other outcomes yielded statistically significant group differences. Conclusion: Physical exercise should be considered in the management of HSCT recipients to improve physical performance after discharge from hospital. Further research is needed to determine how the program can be enhanced so that improved physical performance also translates into improved physical and psychosocial functioning in daily life