Short-term and long-term outcome of radiological-guided insertion of central venous access port devices implanted at the forearm: a retrospective monocenter analysis in 1704 patients.

OBJECTIVES: The objectives are to analyze the technical success rate as well as the short-term and long-term complications of totally implantable venous access ports (TIVAPs) at the forearm. METHODS: Retrospective analysis of 1,704 consecutively implanted TIVAPs was performed. Primary endpoints were defined as technical success rate, clinical outcome, device service interval, and rates of major complications. Minor complications not requiring port explantation were defined as secondary endpoints. RESULTS: The technical success rate was 99.2 % with no major complications. During follow-up, a total of 643,200 catheter-days were documented, the mean device service interval was 380.6 days/patient. A total of 243 complications (14.4 %) in 226 patients were observed (0.4/1000 catheter-days), in 140 patients (8.3 %) the port device had to be explanted. Disconnection between the port device and the catheter (1.6 %) was more frequent than fracture (0.8 %) and leakage (0.6 %) of the catheter, which occurred more frequently when the catheter was inserted via the cephalic versus the brachial vein. CONCLUSION: TIVAP implantation at the forearm is a simple and safe procedure with a low rate of early and late complications.

Effect of antiresorptive drugs on bony turnover in the jaw: denosumab compared with bisphosphonates.

Osteonecrosis of the jaw as a result of treatment with receptor activators of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab) is a new type of bony necrosis, the exact pathogenesis of which is unknown. Our aim was to find out whether the turnover of bone in the jaw is increased after denosumab has been given compared with other skeletal sites, and if that turnover might have a role in denosumab-related osteonecrosis of the jaw (DRONJ). Bone scintigraphic images of 45 female patients with breast cancer and bone metastases were analysed retrospectively, and divided into 3 groups: those given denosumab, those given a bisphosphonate, and a control group (n=15 in each). All patients had bone scintigraphy before treatment (T0) and during the course of treatment after 12 (T1) and 24 (T2) months. The data were analysed quantitatively using 6 preset bony regions of interest. There was similar turnover of bone in the mandible compared with other skeletal sites (such as the femur), while the maxilla showed significantly higher turnover. None of the bony regions investigated showed any significant changes after the bisphosphonate had been given. There was a tendency to increase bone turnover in those patients taking denosumab. The bone turnover of the jawbone is not overtly changed either by a bisphosphonate or denosumab, so it seems unlikely that oversuppression of bony turnover in the jawbones plays an important part either in the pathogenesis of DRONJ or in the bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Is bone turnover of jawbone and its possible over suppression by bisphosphonates of etiologic importance in pathogenesis of bisphosphonate-related osteonecrosis?

PURPOSE: The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood. The most popular hypothesis has suggested that the bone turnover (BT) in the jawbone is greater than that in other sites and that this turnover will be overly suppressed by bisphosphonates. Using bone scintigraphy, a simple tool for the quantitative evaluation of bone metabolism and blood flow, the goals of the present study were to determine whether the rate of bone remodeling is greater in the jaw and whether the bone BT in the jaw is differentially altered after bisphosphonate intake compared with that in other skeletal sites. MATERIALS AND METHODS: The bone scintigraphies of 90 female patients with breast cancer were retrospectively analyzed (n = 45 with bisphosphonate intake; n = 45 without bisphosphonate intake [control group]). All patients in the study group had undergone bone scintigraphy before therapy and during the treatment (course after 12 and 24 months). The data were quantitatively analyzed using 6 predetermined regions of interest. RESULTS: The bone BT of the mandible was similar to that of the femur and significantly reduced compared with that of the maxilla (P < .01). None of the investigated bone regions (including the mandible and maxilla) were significantly altered after bisphosphonate administration (P > .05). CONCLUSIONS: The finding that the mandible had significantly lower bone BT than that of the maxilla and that two thirds of BRONJ cases occur in the mandible were inconsistent with the investigated hypothesis. Furthermore, the bone BT in the jawbone was not overly suppressed by bisphosphonates. Thus, it is unlikely that over suppression of bone BT is the exclusive causation playing a role in the pathomechanism of BRONJ.

A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire.

The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a 'liquid biopsy' with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characterization. For this purpose, we functionalized a structured medical Seldinger guidewire (FSMW), normally used to obtain safe access to blood vessels and other organ cavities, with a chimeric monoclonal antibody directed to the cell surface expressed epithelial cell surface adhesion molecule (EpCAM). This medical device was optimized in vitro and its biocompatibility was tested according to the regulations for medical devices and found to be safe with no noteworthy side effects. Suitability, specificity and sensitivity of the FSMW to catch and enrich CTCs in vivo from circulating peripheral blood were tested in 24 breast cancer or non-small cell lung cancer (NSCLC) patients and in 29 healthy volunteers. For this, the FSMW was inserted through a standard venous cannula into the cubital veins of healthy volunteers or cancer patients for the duration of 30 min. After removal, CTCs were identified by immuno-cytochemical staining of EpCAM and/or cytokeratins and staining of their nuclei and counted. The FSMW successfully enriched EpCAM-positive CTCs from 22 of the 24 patients, with a median of 5.5 (0-50) CTCs in breast cancer (n=12) and 16 (2-515) CTCs in NSCLC (n=12). CTCs could be isolated across all tumor stages, including early stage cancer, in which distant metastases were not yet diagnosed, while no CTCs could be detected in healthy volunteers. In this observatory study, no adverse effects were noted. Evidently, the FSMW has the potential to become an important device to enrich CTCs in vivo for monitoring the course of the cancer disease and the efficacy of anticancer treatment.

Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) are two of the few tumor tissue-associated cancer biomarkers that have been evaluated successfully and extensively in many preclinical and clinical studies for their clinical utility. Most of the studies have been conducted in early breast cancer to demonstrate the prognostic and predictive value for this malignancy. As a result of these investigations, uPA and PAI-1 have reached the highest level of clinical evidence, level of evidence 1. This article sheds light on the current status of major clinical Phase II and III breast cancer therapy trials (Chemo-N0, NNBC-3 and Plan B), and introduces ongoing clinical trials targeting uPA in advanced cancers of the breast and pancreas, employing synthetic small-size drugs to counteract uPA activity (WX-UK1, Mesupron(®)). The therapeutic effect of a uPA-derived small-size synthetic peptide (Å6) is tested in advanced ovarian cancer patients.