Introduction of embryonic stem cells into vein grafts reduces intimal hyperplasia in mice.

AIM: Atherosclerosis with its cardiovascular events including cardiac and peripheral ischemia represents the main cause of death in the developed countries. Although interventional treatments like percutaneous transluminal angioplasty or stents are increasingly applied for the treatment of peripheral arterial disease, they are not always technically applicable or durable and bypass surgery is needed. Compared to synthetic grafts, vein grafts show a better patency especially when used for the lower leg as well as a lower risk for infection compared to synthetic grafts. Still the long-term patency rates are unsatisfactory due to accelerated intimal hyperplasia, a thickening of the vessel wall. The aim of this study was to elucidate, if the implantation of embryonic stem cells into vein grafts can reduce the development of intimal hyperplasia in a mouse in vivo model. METHODS: In this study we implanted LacZ-tagged (ROSA26) murine embryonic stem cells into decellularized vein grafts. Control groups were: 1) untreated veins; 2) decellularized veins; 3) decellularized veins with gel and plastic film; and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film. Six weeks after insertion into the carotid artery of mice, the grafts were excised and analyzed immunohistochemically, morphologically, and by x-gal staining and compared to the control groups. The Mann-Whitney U test was used to compare groups. Statistical significance was indicated by a value of P<0.05. RESULTS: Decellularized veins with implanted stem cells showed significantly less intimal thickening compared to all control groups (intimal hyperplasia vs. luminal circumference mean±SD 7.3±3.5 µm, median 8 µm). The control groups: 1) untreated veins (60.3±25.5 µm, median 58.5 µm); 2) decellularized veins (53.9±22.4 µm, median 48.4 µm); 3) decellularized veins with gel and plastic film (70.6±22.4 µm, median 72.6 µm); and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film (73.5±18.1 µm, median 73.6 µm) all showed the same high degree of intimal hyperplasia. CONCLUSION: This study demonstrates that embryonic stem cells have a therapeutic competence to favourably modulate intimal hyperplasia in vivo.

Novel chimney-graft technique for preserving hypogastric flow in complex aortoiliac aneurysms.

We describe the feasibility and result of a novel approach to preserve pelvic perfusion during endovascular aortoiliac aneurysm repair (EVAR) in patients with aortoiliac aneurysms extending to the iliac bifurcation. The iliac chimney-graft technique consists of the deployment of a ViaBahn™ graft into the hypogastric artery in combination with standard abdominal aortic stent-grafts. The chimney graft was deployed using a transsubclavian access and placed parallel with the iliac limb into the standard aortic stent graft, which was deployed directly before. The technical procedure was successful. Postoperative control showed a sufficiently excluded aneurysm without evidence of endoleak and good distal perfusion of both iliac arteries. The CT-scan after 6 months confirmed the result. The chimney-graft stent grafts to maintain perfusion to hypogastric arteries are feasible and provide an alternative to hypogastric artery exclusion or branched grafts. Long-term follow-up is needed to evaluate stent-graft patency and failure rates.

Novel chimney-graft technique for preserving hypogastric flow in complex aortoiliac aneurysms.

We describe the feasibility and result of a novel approach to preserve pelvic perfusion during endovascular aortoiliac aneurysm repair (EVAR) in patients with aortoiliac aneurysms extending to the iliac bifurcation. The iliac chimney-graft technique consists of the deployment of a ViaBahn™ graft into the hypogastric artery in combination with standard abdominal aortic stent-grafts. The chimney graft was deployed using a transsubclavian access and placed parallel with the iliac limb into the standard aortic stent graft, which was deployed directly before. The technical procedure was successful. Postoperative control showed a sufficiently excluded aneurysm without evidence of endoleak and good distal perfusion of both iliac arteries. The CT-scan after 6 months confirmed the result. The chimney-graft stent grafts to maintain perfusion to hypogastric arteries are feasible and provide an alternative to hypogastric artery exclusion or branched grafts. Long-term follow-up is needed to evaluate stent-graft patency and failure rates.

Outcome of patients with open and endovascular repair in acute complicated type B aortic dissection: a systematic review and meta-analysis of case series and comparative studies.

AIM: Acute complicated type B aortic dissection is a life-threatening condition. We summarized all published studies for TEVAR among patients with acute complicated typ B aortic dissection (TBAD) with respect to clinical success, complications, and outcomes. Furthermore, we determined whether TEVAR reduces death and morbidity compared with open repair for TBAD. METHODS: Studies were identified from a literature search using various databases, and included studies when three or more patients were reported and at least in-hospital mortality was reported. Data from comparative studies of TEVAR versus open repair of the descending aorta in TBAD were combined through meta-analysis. RESULTS: Seventy-six observational studies involving 1951 patients were included in the present meta-analysis. In-hospital mortality was 11.5% and other major complications (i.e., stroke (6.3%), paraplegia (4.9%), retrograde type A aortic dissection (7%), renal impairment including dialysis (6.9%), bowel infarction (4.1%), vascular problems including major amputation (2.5%)) occurred less frequently. Long-term follow-up was limited to a mean of 24 months. During this time, endovascular reintervention was required in 11.3%, surgical reintervention in 7.7%, and late aortic rupture was calculated for 3.2% of cases. A complete false lumen thrombosis was estimated to occur in 76.1% of cases. In comparative studies, 30-day/in-hospital mortality (OR=0.256, P=0.001) and paraplegia/paraparesis (OR=0.256, P=0.001) were significantly reduced for TEVAR versus open repair. In addition to that, the rate of vascular complications was reduced for TEVAR (OR=0.373, P=0.036). There was no significant difference between TEVAR and open repair in patients with acute complicated TBAD for the following outcomes: late mortality, reintervention rate, renal dysfunction (including dialysis), and stroke rate. CONCLUSION: This summary analysis suggests that endovascular treatment of complicated acute type B aortic dissection produces favourable initial outcomes and would seem to be a great addition to the treatment options for this condition. Further study of long-term outcomes is required.

Outcome of carotid endarterectomy under local anaesthesia with respect to the patients' risk profile.

BACKGROUND: In the present study the perioperative complication rate is compared between high- and low-risk patients when carotid endarterectomy (CEA) is routinely performed under local anaesthesia (LA). PATIENTS AND METHODS: From January 2000 through June 2008 1220 consecutive patients underwent CEA under LA. High-risk patients fulfilled at least one of the following characteristics: ASA 4 classification, "hostile neck", recurrent ICA stenosis, contralateral ICA occlusion, age > or = 80 years. The combined complication rate comprised any new neurological deficit (TIA or stroke), myocardial infarction or death within 30 days after CEA, which was compared between patient groups. RESULTS: Overall 309 patients (25%) were attributed to the high-risk group, which differed significantly regarding sex distribution (more males: 70% vs. 63%, p = 0.011), neurological presentation (more asymptomatic: 72% vs. 62%, p = 0.001) and shunt necessity (33% vs. 14%, p < 0.001). In 32 patients 17 TIAs and 15 strokes were observed. In 3 patients a myocardial infarction occurred. Death occurred in one patient following a stroke and in another patient following myocardial infarction, leading to a combined complication rate of 2.9% (35/1220). In the multivariate analysis only previous neurological symptomatology (OR 2.85, 95% CI 1.38-5.91) and intraoperative shunting (OR 5.57, 95% CI 2.69-11.55) were identified as independent risk factors for an increased combined complication rate. CONCLUSIONS: With the routine use of LA, CEA was not associated with worse outcome in high-risk patients. Considering the data reported in the literature, it does not appear justified to refer high-risk patients principally to carotid angioplasty and stenting (CAS) when LA can be chosen to perform CEA.

Meta-analysis of subfascial endoscopic perforator vein surgery (SEPS) for chronic venous insufficiency.

OBJECTIVES: The degree of benefits and risks, and the role of subfascial endoscopic perforator vein surgery (SEPS) in the management for chronic venous insufficiency (CVI) remains uncertain. METHODS: A multiple health database search was performed including Medline, Embase, Ovid, Cochrane Database of Systematic Reviews, and Cochrane Database of Abstracts of Reviews of Effectiveness, on all studies published between 1985 and 2008 that reported on health outcomes in patients with CVI treated with SEPS and comparing this therapy with the conventional Linton procedure. Three studies, which compared SEPS with conventional surgery, were included in the present meta-analysis. RESULTS: Between SEPS and Linton groups, there was a significant lower rate of wound infections for SEPS (odds ratio [OR] 0.06 [95% confidence interval (CI) 0.02 to 0.25]) and a significantly reduced hospital stay for SEPS (OR -8.96 [95% CI -11.62 to -6.30]). In addition, SEPS was associated with a significant reduced rate of recurrent ulcers (mean follow-up 21 months) (OR 0.15 [95% CI 0.04-0.62]). There was no significant difference between the groups in the following dimensions: rate of hospital re-admission (OR 0.21 [95% CI 0.03-1.31]), death at six months (OR 3.00 [95% CI 0.11-78.27]), ulcer healing rate at four months (OR 0.44 [95% CI 0.09-2.12]), and the rate of deep vein thrombosis (DVT) (OR 0.35 [95% CI 0.01-8.85]). CONCLUSION: From the level of evidence available by now it seems that SEPS, used as a part of a treatment regimen for severe CVI, benefits most patients in the short term regarding ulcer healing and the prevention of ulcer recurrence. It can be safely performed with less early postoperative complications compared with the Linton procedure. However, further prospective randomized trials are required to define the long-term benefits of SEPS.

Meta-analysis of transilluminated powered phlebectomy for superficial varicosities.

AIM: The purpose of the present meta-analysis was to analyze the data available concerning the transilluminated powered phlebectomy (TIPP). METHODS: A multiple electronic health database search was performed including Medline, Embase, Ovid, Cochrane Database of Systematic Reviews, and Cochrane Database of Abstracts of Reviews of Effectiveness (DARE), on all studies published between 1996 and 2007 that reported about health outcomes in patients with cardiovascular insufficiency (CVI) treated with TIPP and comparing this therapy with the conventional procedure. Five studies, that compared TIPP with conventional surgery, were included in the present meta-analysis. RESULTS: Currently, these data clearly proved significant statistical advantage of TIPP technique over the conventional treatment, only for number of incisions, mean cosmetic score and duration of the procedure. However, TIPP technique seemed to be faster only for extensive varicose veins. There was, however, a significantly reduced incidence of calf hematoma after hook phlebectomy compared to TIPP, and TIPP procedure was associated with a worse mean pain score. CONCLUSION: Further randomized trials are needed to determine the benefit of this procedure.

Endovascular therapy of a symptomatic mobile thrombus of the thoracic aorta.

INTRODUCTION: The therapeutic strategies of a mobile luminal thrombus of the descending thoracic aorta with peripheral arterial embolization remain a matter of debate. REPORT: We report the case of recurrent peripheral arterial embolism caused by a mobile thrombus of the descending aorta, which was successfully treated by implanting an endovascular stent graft. DISCUSSION: Our case demonstrates, that endovascular stent graft placement is feasible and can be performed as an effective and minimally invasive treatment option for mobile thoracic aortic thrombi.

Systematic review and meta-analysis of endovenous radiofrequency obliteration, endovenous laser therapy, and foam sclerotherapy for primary varicosis.

AIM: Radiofrequency obliteration (RFO), endovenous laser therapy (EVLT) and foam sclerotherapy (FS) are potential treatments for varicose veins. A systematic review was undertaken to assess their safety and effectiveness and to compare these endoluminal therapeutic options with conventional ligation and vein stripping. METHODS: An electronic health database search was performed on all studies published between 1970 and 2007 describing RFO, EVLT, and FS for treating varicose veins. RESULTS: Twenty-nine EVLT studies, 32 RFO studies and 22 FS trials were included. RFO was associated with the worst short and long-term safety and efficacy results compared to EVLT and FS regarding ''complete occlusion at the end of follow-up'', ''phlebitis'', ''deep vein thrombosis'', and ''paraesthesia''. EVLT had the best results concerning the long-term effectiveness parameters for ''occlusion at the end of follow-up'' and ''recanalization, recurrence or development of new veins'', compared to RFO and FS. Foam sclerotherapy of varicose veins is associated with a higher recurrence rate in patients with saphenofemoral incompetence compared to the rates after EVLT or RFO treatment. CONCLUSION: EVLT, RFO, and FS seem to be safe and effective modalities with good short and mid-term RESULTS: Acquisition of comparative long-term and very long-term data on clinical efficacy (particularly with regard to the formation of recurrent varicose veins), safety, quality of life outcomes and costs is needed by large high-quality prospective randomized trials of endovenous techniques versus each other and versus surgery before considering endovenous techniques as the standard treatment.

Meta-analysis of randomized trials comparing carotid endarterectomy and endovascular treatment.

OBJECTIVE AND DESIGN: In order to evaluate the comparative efficacy and safety of carotid angioplasty with or without stent placement (CAS) versus carotid endarterectomy (CEA) we performed a meta-analysis of the presently available randomized studies. MATERIALS AND METHODS: A multiple electronic health database search on all randomized trials describing CAS compared with CEA in patients with symptomatic or asymptomatic carotid artery stenosis was performed. RESULTS: Seven trials totalling 2972 patients (1480 randomized to CEA and 1492 randomized to CAS) were included in the meta-analysis. Results significantly favoured CEA over CAS in terms of death or any stroke at 30 days after procedure; the risk of death, any stroke, or myocardial infarction at 30 days; ipsilateral ischaemic stroke at 30 days; any stroke at 30 days; death or stroke at 6 months; and the risk of procedural failure. There was a significantly reduced risk of cranial neuropathy at 30 days after CAS. There was no significant difference between CAS and CEA groups in the odds of death or disabling stroke at 30 days, death or stroke at 1 year after the procedure, and ipsilateral intracerebral bleeding at 30 days. CONCLUSIONS: The results of this meta-analysis suggest that CEA can be performed with more safety than CAS. As a result, CEA remains the "gold standard" treatment for suitable de novo carotid stenosis and CAS should only be performed within randomized trials of stenting versus surgery.

Combined endovascular-open surgical procedure in a great hepatic artery aneurysm.

Visceral artery aneurysms are rare lesions. They involve the hepatic artery in approximately 20% of cases. Various therapeutic options are available for patients with hepatic artery aneurysms (HAAs). Dictated predominately by the need to maintain distal end-organ perfusion, potential therapies include traditional surgical techniques and laparoscopic surgery, endovascular methods of embolization, and stenting of the lesions. There is still a lack of studies demonstrating the comparative efficacy or inefficacy of any particular treatment, so there are currently no precise indications for determining which type of treatment should be used. In this paper, we present a case of great HAA in a 59-year-old man. He was preoperatively diagnosed and treated with a combined surgical and endovascular approach. The clinical presentation, management, and therapy of patients with HAAs are discussed. In addition to that, we reviewed the literature dealing with HAAs. This case report lays emphasis on the aspect that the treatment strategy in HAAs has to be determined individually in each case due to the high anatomic variability of the arterial supply of the liver. Treatment with a combined surgical and endovascular approach may reduce the risk of liver ischemia and morbidity.

Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers.

BACKGROUND AND OBJECTIVES: We evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with various gastrointestinal cancers and if they decrease following complete surgical resection. METHODS: Blood samples from 40 gastrointestinal cancer patients were analyzed prior and following surgical resection by direct quantitative real-time reverse transcriptase-PCR (RT-PCR) assays. RESULTS: Survivin mRNA expression was pre-operatively detected in 35 of 40 cancer patients (88%). Post-operative survivin levels were significantly lower than pre-operative levels in 59% of resected patients and were non-detectable in 38% (Wilcoxon rank test: P < 0.04). CONCLUSIONS: This is the first report showing that direct quantitative real-time RT-PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection.

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

Feasibility of sentinel node concept in gastric carcinoma: clinicopathological analysis of gastric cancer with solitary lymph node metastases.

BACKGROUND: The feasibility and diagnostic reliability of sentinel lymph node biopsy of gastric carcinoma are still unclear and controversial. PATIENTS AND METHODS: To assess the applicability of the sentinel node concept to gastric carcinoma, we retrospectively analyzed the location of metastatic lymph nodes in patients with only one or two lymph node metastases. RESULTS: A total of 135 patients, who underwent gastrectomy with D2 lymphadenectomy for primary gastric adenocarcinoma between 1997 and 2001, were enrolled in this study. An average of 39 lymph nodes were resected and analyzed for each patient. Of the 135 patients, 88 (65%) were subtyped as pN+ (with lymph node metastasis); of the latter, 15 cases (pT1-3; 17% of N+ cases) showed one or two lymph node metastases. In 14 (93%) of these patients, lymph nodes directly adjacent to the primary tumor were involved. Skip metastases were only seen in one patient with cardia carcinoma and lymph node involvement of compartment II (left gastric artery). CONCLUSION: In patients with gastric carcinoma, especially in early stage carcinoma, the phenomenon of skip metastasis is infrequent. Therefore, the sentinel node concept may be feasible in gastric cancer.

Masaoka staging is of prognostic relevance in type B3 / C thymomas.

BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index (LI) with the Masaoka classification and the new WHO-classification in type B3 / C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas were evaluated, and archived specimens were histologically reclassified according to Masaoka staging, the new WHO classification and the Ki-67 LI in a retrospective analysis. RESULTS: Four patients presented with Masaoka stage II disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3 WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C). The statistical analysis revealed a significant correlation between Masaoka staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in patients with type B3 / C thymoma whereas WHO-classification did not (p = 0.3266). Between survivors and non-survivors there was no statistically significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study indicated that the Masaoka staging system is of prognostic relevance in type B3 / C thymomas.

A gulf of difference: disputes over Gulf War-related illnesses.

The social discovery of Gulf War-related illnesses, like other occupational and environmental disease, is firmly rooted in ongoing disputes over causation. Pressure from veterans groups, as well as intra-governmental disputes, have driven innovative research directions and challenged the dominant epidemiological paradigm. This dominant epidemiological paradigm was originally a position that viewed stress as the primary causal factor. In the emerging dominant epidemiological paradigm, researchers view veterans' symptoms as similar to other multi-symptom diseases and conditions, but with a firmer respect for the reality of those symptoms. In addition, some researchers pursue interactions between stress and physical exposure. We examine the evolution of the DEP to demonstrate that in many disease disputes, an affected population challenges government and science decision-making, and even ways of knowing, in an attempt to negotiate a disease definition and etiology that results in better treatment and prevention. After considerable research effort, only limited evidence has been found for environmental causation, and even many researchers sympathetic to veterans are doubtful that much more will be found. We analyze the social discovery and ongoing contestation of these illnesses, and the consequent effects on health and public policy. For extension to other disease disputes, we provide an overall model of disease discovery and contestation, examining the key forces of government, science, and citizens.

Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients.

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined by the American College of Chest Physicians/Society of Critical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 septic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined in serum. In some experiments, IL-18 mRNA levels were determined in peripheral blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 levels were significantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment. These data might underscore the role of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue damage. Furthermore, these findings raise the notion that mediator measurement in immunologically active organs might serve as pivotal indicators of sepsis prior to the actual fulfillment of specific clinical criteria that defines the patient as being septic.

Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses.

The effect of acetyl - tyrosyl-valyl-alanyl-aspartyl - chloromethylketone (ac-YVAD-cmk), an irreversible caspase-1 (IL-1beta converting enzyme, ICE) inhibitor on mortality, leukocyte and platelet counts and cytokine levels was investigated in a double-blind rat model of endotoxaemia. Intravenous (i.v.) bolus administration of lipopolysaccharide (LPS) (25-75 mg kg(-1), n=12 per group) to anaesthetized rats induced a dose dependent increase in mortality over 8 h (LD(50)=48 mg kg(-1)). During this period, animals became leukopenic and thrombocytopenic. Serum levels of IL-beta, IL-6, and TNF-alpha were highly elevated. Pretreatment of rats with ac-YVAD-cmk at a dose of 12.5 micromol kg(-1) significantly reduced mortality from 83 to 33% using Log Rank analysis. However, ac-YVAD-cmk did not modify blood cell counts or cytokine profiles as compared with the LPS-drug vehicle group. These data lay credence to the potential importance of caspase-1-inhibition in modifying the inflammatory response to endotoxin. Further investigations are warranted in understanding the relationship between caspase-1 inhibition, cytokine production and animal survival in different experimental paradigms of sepsis.