Primary angiosarcoma of the abdominal aorta: multi-row computed tomography

Primary angiosarcoma of the aorta is a rare tumor. The symptoms resemble those of atherosclerotic occlusive disease, and the radiomorphologic pattern is often nonspecific. In most published cases, the malignant vascular obstruction was diagnosed histopathologically after surgical vascular reconstruction. We report on interventional and CT-angiographic features of an abdominal aortic angiosarcoma, observed in a 71-year-old patient. The polyploid intimal alteration is clearly depicted on CT images. Morphology and the segmental obstruction of the aortic lumen without aneurysmal or extensive atherosclerotic mural changes should lead to the differential diagnosis of an intravascular malignanc

Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention

BACKGROUND: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites. METHODS: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h. RESULTS: URO transiently increased urine sodium excretion from 22 ± 16 μmol/min (mean ± SD) to 78 ± 41 μmol/min (P < 0.05) and there was no effect of placebo (29 ± 14 to 44 ± 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these. CONCLUSION: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO

Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: A phase II-study and historical comparison with the surgical approach

<p>Abstract</p> <p>Background</p> <p>The high complication rates of surgically implanted port catheter systems (SIPCS) represents a major drawback in the treatment of isolated liver neoplasms by hepatic arterial infusion (HAI) of chemotherapy. Interventionally implanted port catheter systems (IIPCS) have evolved into a promising alternative that enable initiation of HAI without laparatomy, but prospective data on this approach are still sparse. Aim of this study was to evaluate the most important technical endpoints associated with the use of IIPCS for the delivery of 5-fluorouracil-based HAI in patients with colorectal liver metastases in a phase 2-study, and to perform a non-randomised comparison with a historical group of patients in which HAI was administered via SIPCS.</p> <p>Methods</p> <p>41 patients with isolated liver metastases of colorectal cancer were enrolled into a phase II-study and provided with IIPCS between 2001 and 2004 (group A). The primary objective of the trial was defined as evaluation of device-related complications and port duration. Results were compared with those observed in a pre-defined historical collective of 40 patients treated with HAI via SIPCS at our institution between 1996 and 2000 (group B).</p> <p>Results</p> <p>Baseline characteristics were balanced between both groups, except for higher proportions of previous palliative pre-treatment and elevated serum alkaline phosphatase in patients of group A. Implantation of port catheters was successful in all patients of group A, whereas two primary failures were observed in group B. The frequency of device-related complications was similar between both groups, but the secondary failure rate was significantly higher with the use of surgical approach (17% vs. 50%, p < 0.01). Mean port duration was significantly longer in the interventional group (19 vs. 14 months, p = 0.01), with 77 vs. 50% of devices functioning at 12 months (p < 0.01). No unexpected complications were observed in both groups.</p> <p>Conclusion</p> <p>HAI via interventionally implanted port catheters can be safely provided to a collective of patients with colorectal liver metastases, including a relevant proportion of preatreated individuals. It appears to offer technical advantages over the surgical approach.</p

A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer

BACKGROUND: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. METHODS: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m(2 )twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m(2 )for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. RESULTS: Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. CONCLUSION: There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent

A prospective randomized multicenter trial comparing histidine-tryptophane-ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation

We aimed to evaluate early pancreas transplant graft function after histidine-tryptophan-ketoglutarate (HTK) versus University of Wisconsin (UW) perfusion. Prospective randomized multicenter study including 68 pancreas transplantations stratified according to preservation fluid used (27 HTK vs. 41 UW). Primary endpoint was pancreas graft survival at 6 months. Serum alpha-amylase, lipase, C-peptide, HbA1C and exogenous insulin requirement were compared at several time points. Mean pancreas cold ischemia time was 10.8 +/- 3.7 (HTK) vs. 11.8 +/- 3.4 h (UW) (P = 0.247). Simultaneous pancreas-kidney transplantation was performed in 95.6% of the patients, pancreas transplantation alone in 2.9%, and pancreas after kidney transplantation in 1.5%. Six months graft survival was 85.2% (HTK) vs. 90.2% (UW) (P = 0.703). Serum amylase and lipase values did not differ between both the groups during the observation period. C-peptide levels were elevated in both the groups without significant differences at each time point. Higher exogenous insulin requirement early after transplantation in the UW group had resolved at 3 months. Six month patient survival was 96.3% (HTK) vs. 100% (UW) (P = 0.397). With a mean cold ischemia time of 10 h in this study, HTK and UW solutions appear to be equally suitable for perfusion and organ preservation in clinical pancreas transplantation

Synthesis of C-X-C and C-C Chemokines by Human Peritoneal Fibroblasts : Induction by Macrophage-Derived Cytokines

Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1β and tumor necrosis factor-α. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1β as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1β and tumor necrosis factor-α produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-κB binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein κB-α proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-κB/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis