Randomized clinical trial of endovenous laser ablation versus direct and indirect radiofrequency ablation for the treatment of great saphenous varicose veins.

BACKGROUND: The current treatment strategy for many patients with varicose veins is endovenous thermal ablation. The most common forms of this are endovenous laser ablation (EVLA) and radiofrequency ablation (RFA). However, at present there is no clear consensus on which of these treatments is superior. The objective of this study was to compare EVLA with two forms of RFA: direct RFA (dRFA; radiofrequency-induced thermotherapy) and indirect RFA (iRFA; VNUS ClosureFast™). METHODS: Patients with symptomatic great saphenous vein (GSV) incompetence were randomized to receive EVLA, dRFA or iRFA. Patients were followed up at 2 weeks, 6 and 12 months. The primary outcome was GSV occlusion rate. Secondary outcomes included Venous Clinical Severity Score (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ) score and adverse events. RESULTS: Some 450 patients received the allocated treatment (EVLA, 148; dRFA, 152; iRFA, 150). The intention-to-treat analysis showed occlusion rates of 75·0 (95 per cent c.i. 68·0 to 82·0), 59·9 (52·1 to 67·7) and 81·3 (75·1 to 87·6) per cent respectively after 1 year (P = 0·007 for EVLA versus dRFA, P < 0·001 for dRFA versus iRFA, P = 0·208 for EVLA versus iRFA). VCSS improved significantly for all treatments with no significant differences between them. AVVQ scores also improved significantly for all treatments, but iRFA had significantly better scores than dRFA at 12 months. Significantly more adverse events were reported after treatment with EVLA (103) than after dRFA (61) and iRFA (65), especially more pain. CONCLUSION: Primary GSV occlusion rates were better after iRFA and EVLA than dRFA. All three interventions were effective in improving the clinical severity of varicose veins at 1 year.

Bilateral catheter-directed thrombolysis in a patient with deep venous thrombosis caused by a hypoplastic inferior vena cava.

INTRODUCTION: Deep venous thrombosis treatment using catheter-directed thrombolysis is advocated over systemic thrombolysis because it reduces bleeding complications. With the development of a catheter that combines ultrasound vibrations and the local delivering of thrombolytics, new and safer treatments appear that are suitable for more complex problems. REPORT: An adolescent male presented with bilateral iliofemoral thrombosis based on a hypoplastic inferior vena cava that had existed for more than two weeks. He was successfully treated by bilateral ultrasound-accelerated catheter-directed thrombolysis using EkoSonic® (Small Vessel) Endovascular System (EKOS) and stenting of the inferior vena cava. After eight months of follow-up, the inferior vena cava is still patent. CONCLUSION: EKOS thrombolysis of longer existing bilateral deep venous thrombosis in the central venous system is a successful treatment modality in congenital inferior vena cava anomalies.

Death and venous thromboembolism after lower extremity amputation.

BACKGROUND: Lower extremity amputation is often performed in patients with end-stage vascular disease and is considered a high-risk procedure. Uncertainty exists about the rate of venous thromboembolism (VTE) in these patients. OBJECTIVES: To establish the incidence of death and venous thromboembolism after lower extremity amputation. METHODS: A prospective cohort study was performed to establish the incidences of death and VTE after lower extremity amputation, as detected by bilateral complete compression ultrasonography and ventilation-perfusion scintigraphy performed preoperatively and around day 14 postoperatively. Standard low-molecular-weight heparin thromboprophylaxis was given during the study period. A secondary outcome was the incidences of mortality and symptomatic venous thromboembolic complications during 8 weeks of postoperative follow-up. RESULTS: Forty-nine patients (53 amputations) were ultimately included in the intention-to-treat analysis. Five patients died within the 2-week period and an additional seven patients died during the 8 weeks clinical follow-up period. The total mortality rate therefore was 12 of 53 amputations [22.6%; 95% confidence interval (CI), 12.3-36.2%]. Six patients developed pulmonary embolisms (of which two were fatal) and one patient developed an asymptomatic contralateral distal deep venous thrombosis, resulting in a total VTE rate of 7 out of 53 amputations (13.2%; 95% CI, 5.47-25.3%). CONCLUSION: Lower extremity amputation is accompanied by a high mortality rate from sepsis, and respiratory and vascular causes. This study shows that VTE substantially contributes to the morbidity and mortality after lower extremity amputation despite adequate pharmacological thromboprophylaxis in this vulnerable population of patients.

Performance of ePTFE-covered endograft in patients with occlusive disease of the superficial femoral artery: a three-year clinical follow-up study.

AIM: Feasibility of ePTFE-covered endoprosthesis for treatment of atherosclerotic stenosis or occlusions of the SFA. This was a prospective follow-up study on intention-to-treat basis. ePTFE-covered endoprosthesis were used. METHODS: From November 2001 to December 2006, 96 patients were treated for invalidating claudication, critical ischemia or gangrene. ABI and ischemia severity score according to Rutherford were defined. Morphology of the lesions was classified according to the Trans-Atlantic InterSociety Consensus. Clinical outcome was investigated by ABI, Duplex-ultrasound, and luminal diameter measurements inside grafts. Follow-up visits were conducted at six weeks and six months, and yearly thereafter. RESULTS: Significant clinical improvement was achieved in all patients. ABI increased to normal, and did not fall during three-year follow-up. Kaplan-Meier estimates for primary patency were 76% (N.=77), 70% (N.=56) and 67.7% (N.=40), and for secondary patency 86.9% (N.=85), 82.2 (N.=63) and 79.8% (N.=45) at 1, 2, and 3 years. Intraluminal graft diameters did not decrease significantly during follow-up. Graft occlusion was seen in 21/96 endografts; 20 patients underwent additional PTAs, only three patients had intragraft stenosis. Occluded grafts did not show reduction of luminal diameters on follow-up examinations before occlusion. CONCLUSION: ePTFE-covered endografts have excellent properties for treatment of SFA stenosis or occlusions. There was no intimal hyperplasia inside endografts, and graft occlusion occurred due to progression of atherosclerotic disease outside the graft.

Treatment of dilated venous bypass grafts with an expanded polytetrafluoroethylene-covered nitinol endoprosthesis.

An above-knee femoropopliteal bypass graft constructed of great saphenous vein became dilated in 2 patients 12 and 25 years after surgery. Both patients had several concomitant disorders. The dilations were treated by insertion of an expanded polytetrafluoroethylene-covered nitinol endoprosthesis. There were no major procedural complications. One minor endoleak that developed immediately after endograft placement resolved within 6 weeks. The leg swelling subsided, and the endoprostheses have remained patent for 18 and 24 months, respectively. To our knowledge, these were the first cases in which an endoprosthesis was used to treat dilation of a venous bypass graft.

Prospective randomized study of carotid endarterectomy with Fluoropassiv thin wall carotid patch versus venous patch.

INTRODUCTION: The practice of carotid endarterectomy (CEA) with patch angioplasty is more effective compared to primary closure. However, the type of patch material remains a controversy. The Fluoropassiv thin wall carotid patch is a polyester patch with an interpenetrating, nanometer-scale, solvent-applied surface modification, based on a biocompatible fluoropolymer. The present pilot study is the first clinical trial evaluating results of CEA with Fluoropassiv versus venous patch. MATERIALS/METHODS: Eighty-seven patients were randomized to 42 Fluoropassiv patching and 45 venous patching. Patients were observed by a vascular surgeon and a neurologist and scanned using duplex ultrasound with a follow-up of 2 years. No patients were lost to follow-up. Restenosis was defined as a Peak Systolic Velocity ratio >2.6, lumen reduction >50%. RESULTS: Perioperative stroke rate was 2.4% in the Fluoropassiv group and 8.9% in the venous group (p=0.02; 1 regressive, 4 non-regressive strokes). Multivariate analysis showed that bilateral carotid stenosis and stroke as indication for CEA were related to perioperative stroke. There was no link between perioperative stroke and patch type after correction for these factors. Patch type had no influence on operation time, clamp time, cranial nerve damage, hypertension, hematoma, infections, time to discharge, or early thromboembolic events. There were no significant differences between the Fluoropassiv and the venous group for cumulative mortality (respectively 4.4 vs 4.8%), patch occlusion (4.8 vs 2.2%), or stroke rate during 2 year follow-up (2.2 vs 2.4%). CONCLUSION: This first clinical study with the Fluoropassiv thin wall carotid patch showed no enhanced thrombogenicity compared to a venous patch. The Fluoropassiv patch is not related to a higher rate of postoperative bleeding events either.

[Deep venous thrombosis in an amputation stump]. / Diepveneuze trombose in een amputatiestomp.

A 34-year-old patient underwent a knee exarticulation amputation and developed symptoms of pain, redness and swelling of the stump in combination with a feeling of tightness in the chest. These symptoms were first attributed to muscle pain and exertion but further examination revealed deep venous thrombosis (DVT) of the stump and a pulmonary embolism for which he was treated with nadroparine and acenocoumarol. Shortly after treatment he could resume the use of the prosthesis. A DVT in the amputation stump is not frequently encountered, but is a serious complication that can, together with a pulmonary embolism, be life threatening. The literature mentions an incidence ranging from 0-12%. Physical examination is often not conclusive and further examination of the patient with duplex scanning is necessary, with a ventilation-perfusion scan if a pulmonary embolism is suspected. Patients with a lower extremity amputation have a higher risk of developing a DVT because of immobility and increased venous pooling in the residual limb. Symptoms of a red, swollen, warm and painful stump should trigger the physician to suspect a DVT.

Autogenous radial-cephalic or prosthetic brachial-antecubital forearm loop AVF in patients with compromised vessels? A randomized, multicenter study of the patency of primary hemodialysis access.

OBJECTIVE: The construction of an autogenous radial-cephalic direct wrist arteriovenous fistula (RCAVF) is the primary and best option for vascular access for hemodialysis. However, 10%-24% of RCAVFs thrombose directly after operation or do not function adequately due to failure of maturation. In case of poor arterial and/or poor venous vessels for anastomosis, the outcome of RCAVFs may be worse and an alternative vascular access is probably indicated. A prosthetic graft implant may be a second best option. Therefore, a randomized multicenter study comparing RCAVF with prosthetic (polytetrafluoroethylene [PTFE]) graft implantation in patients with poor vessels was performed. METHODS: A total of 383 consecutive new patients needing primary vascular access were screened for enrollment in a prospective randomized study. According to defined vessel criteria from the preoperative duplex scanning, 140 patients were allocated to primary placement of an RCAVF and 61 patients to primary prosthetic graft implantation. The remaining 182 patients were randomized to receive either an RCAVF (n = 92) or prosthetic graft implant (n = 90). Patency rate was defined as the percentage of AVFs that functioned well after implantation. RESULTS: Primary and assisted primary 1-year patencies were 33% +/- 5.3% vs 44% +/- 6.2% (P = .03) and 48% +/- 5.5% vs 63% +/- 5.9% (P = .035) for the RCAVF and prosthetic AVF, respectively. Secondary patencies were 52% +/- 5.5% vs 79% +/- 5.1% (P = .0001) for the RCAVF and prosthetic AVF, respectively. Patients with RCAVFs developed a total of 102 (1.19/patient-year [py]) vs 122 (1.45/py; P = .739) complications in the prosthetic AVFs. A total of 43 (0.50/py) interventions in the RCAVF group and 79 (0.94/py) in the prosthetic graft group were needed for access salvage (P = .077). CONCLUSIONS: Although there were more interventions needed for access salvage in the patients with prosthetic graft implants, we may conclude that patients with poor forearm vessels do benefit from implantation of a prosthetic graft for vascular access.

Glycol methacrylate embedding of alginate-polylysine microencapsulated pancreatic islets.

A method for processing and embedding alginate-polylysine microencapsulated pancreatic tissue in glycol methacrylate resin (GMA) is described. Fixation in 4% phosphate buffered formaldehyde, processing in ascending concentrations of glycol methacrylate monomer and embedding in Technovit 7100 results in well preserved morphological details of hydrogels, hydrogel-cell interfaces, and encapsulated pancreatic tissue. Routine staining with Loeffler's methylene blue, hematoxylin and eosin, and Romanovsky-Giemsa gave excellent images of the GMA embedded alginate polylysine membrane and tissues allowing cells on the outside of the capsule to be analyzed effectively as part of the foreign body reaction against the capsule membrane.

The capsular overgrowth on microencapsulated pancreatic islet grafts in streptozotocin and autoimmune diabetic rats.

This study investigates whether capsular overgrowth on alginate-polylysine microencapsulated islets is influenced by (1) the presence of islet tissue, (2) MHC incompatibility between donor and recipient, or (3) the presence of autoimmune diabetes. Encapsulated Albino Oxford (AO, n = 6, isografts) and Lewis (n = 6, allografts) rat islets, and encapsulated human islets (n = 5, xenografts) were implanted intraperitoneally into streptozotocin-diabetic AO rats. Also, encapsulated AO islets were implanted into autoimmune diabetic Bio Breeding/Organon (BB/O) rats (n = 5, allografts). Five isografts, five allografts, and three xenografts in AO recipients and five allografts in BB/O recipients resulted in normoglycemia. Two weeks after implantation, islets containing capsules were retrieved by peritoneal lavage, after which all animals that had become normoglycemic after transplantation returned to a state of hyperglycemia. Recovery rates of the capsules of these successful grafts, expressed as percentages of the initially implanted graft volume, varied from 72% +/- 7% to 80% +/- 9%. The associated pericapsular infiltrates (PCI) were similar in all groups and varied from 3.2% +/- 1.4% to 8.3% +/- 2.6%. Similar recovery rates and PCI were also found with empty capsules. However, the recovery rates of recipients with graft failures were lower and showed more PCI. Immunohistological staining of PCI showed no differences in the types of cells in the PCI on capsules with or without islets. We conclude that this early PCI is a capsule-induced foreign body reaction that is not influenced by MHC incompatibility or by the presence of autoimmune diabetes, and it should be avoided by improving the biocompatibility of the capsules.

Obstacles in the application of microencapsulation in islet transplantation.

Several factors stand in the way of successful clinical transplantation of alginate-polylysine-alginate microencapsulated pancreatic islets. These obstacles can be classified into three categories. The first regards the technical aspects of the production process. Limiting factors are the insufficient ability to produce small capsules with an adequate production rate, and insufficient insight into the factors determining the optimal chemical and mechanical properties of the capsules. The second category regards the functional aspects of the microencapsulated islets, such as the limitations of the transplantation site and the absence of a physiologic insulin response of the encapsulated islets to elevated blood glucose levels. The third category regards the fact that survival times of encapsulated islet grafts are still limited to several weeks or months, which is mainly explained by a pericapsular fibrotic overgrowth reaction as a consequence of the bioincompatibility of the capsule membrane. This study describes these obstacles, and thereby summarizes the requirements needed for successful clinical application of encapsulated islet transplantation.

Comparison of top and bottom loading of a dextran gradient for rat pancreatic islet purification.

Rat pancreatic islet yields obtained with dextran gradient purification were compared after suspending the digest into either the top or the bottom layer of the gradient. A 5-layer discontinuous gradient was used, which consisted of 16 ml 31% dextran as bottom layer, overlayered with 25%, 23%, 20% and 11% dextran (4 ml each). When the digest of 1 rat pancreas was suspended into the top layer of the gradient, the total number of islets obtained from the 11-20, 20-23 and 23-25% interfaces was 862 +/- 38, 240 +/- 39 and 54 +/- 5, respectively. From this gradient, also 1409 +/- 81 islets were retrieved from the bottom layer (i.e., exocrine pellet). In contrast, when the pancreas digest was suspended into the bottom layer of the gradient, 1964 +/- 63, 435 +/- 42, and 177 +/- 34 islets were obtained from the successive interfaces, and only 50 +/- 20 islets from the exocrine pellet. The total islet volume obtained from the two uppermost interfaces was 3.46 +/- 0.31 microliters after top-loading, and 4.93 +/- 0.16 microliters after bottom-loading (n = 7, p < 0.01). When the islets retrieved from one bottom loaded gradient were transplanted into either 1 (n = 6) or 2 (n = 9) diabetic recipients, glucose levels normalized in all instances. We therefore conclude that a bottom-loaded dextran gradient separates islets from exocrine tissue effectively, resulting in significantly higher islet yields than obtained with a top-loaded dextran gradient.

The efficacy of intraperitoneal pancreatic islet isografts in the reversal of diabetes in rats.

The peritoneal cavity is of renewed interest for pancreatic islet transplantation, since it is the preferable site for transplantation of immunoisolated islets. In this study we investigated the minimum islet graft volume needed to restore normoglycemia after free intraperitoneal isogenic transplantation in streptozotocin diabetic rats. Furthermore, graft function was tested by measuring glucose and insulin response to an intravenous glucose load and spontaneously ingested carbohydrate-rich meal. Three graft volumes were used: 8.0-10.0 (group A); 4.0-5.0 (group B); and 2.0-2.3 microliters (group C); 1 microliter contained about 300 islets. All 10 rats in group A and 7 out of 9 rats in group B became normoglycemic for at least 6 months posttransplant, with blood glucose levels not significantly different from normal control animals. Only 3 out of 9 animals in group C became normoglycemic and never for longer than 3 months. The insulin responses to IVGTT in group A and group B were proportional to the grafted islet volume and always significantly lower than those of normal control rats. The insulin response to the test meal showed a similar tendency, which was found to be associated with the absence of preabsorptive insulin secretion. Maximum postprandial blood glucose levels in group A and group B were 0.8 and 1.5 mM higher than in normal control rats. We conclude that intraperitoneal transplantation of at least 4.0-5.0-microliters islet tissue is needed to reverse blood glucose in streptozotocin diabetic rats, and that glucose and insulin levels on IVGTT and test meal in rats with islet grafts of 8.0-10.0 microliters are not completely normalized. It is suggested that the impaired glucose tolerance is due to an insufficient beta-cell mass and a lack of parasympathetic innervation of the transplanted islet tissue.

Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts.

Albino Oxford rats made diabetic with 75 mg/kg streptozotocin were intraperitoneally transplanted with 2500-2900 alginate-polylysine microencapsulated Lewis islets (n = 9, total islet tissue volume 8.0-11.0 microliters), or a similar volume of non-encapsulated Lewis islets (n = 5). All rats with microencapsulated islets became normoglycaemic, and remained normoglycaemic for 5-16 weeks. In rats with non-encapsulated islet grafts, only a temporary decrease in blood glucose was observed, and all were again severely hyperglycaemic at 1 week after implantation. At 5-6 weeks after transplantation, glucose tolerance in rats with microencapsulated islets was tested by intravenous glucose infusion (10 mg/min over 20 min) and test meal administration (n = 4). During glucose infusion, maximum glucose levels were 13.0 +/- 0.4 mmol/l in rats with microcapsules and 8.9 +/- 0.4 mmol/l in healthy control rats (p less than 0.01). Concomitant maximum plasma insulin levels were 215 +/- 17 pmol/l in rats with microcapsules and 715 +/- 85 pmol/l in controls (p less than 0.001). After the test meal, maximum blood glucose was 10.6 +/- 0.9 mmol/l in rats with microcapsules and 6.2 +/- 0.1 mmol/l in controls (p less than 0.001), with concomitant maximum plasma insulin levels of 247 +/- 11 pmol/l and 586 +/- 59 pmol/l, respectively (p less than 0.001). In conclusion, although the glucose tolerance is impaired and plasma insulin responses to intravenous glucose-load and test-meal are reduced, the alginate-polylysine membrane does provide adequate immunoisolation for the prolongation of allograft survival, resulting in prolonged normoglycaemia in streptozotocin diabetic rats.

Effect of alginate-polylysine-alginate microencapsulation on in vitro insulin release from rat pancreatic islets.

We investigated the effect of alginate-polylysine-alginate microencapsulation on glucose-induced insulin secretion by rat islets. Applying the encapsulation method originally described by Lim, we found severely reduced in vitro insulin release (expressed as picomoles of insulin.10 islets-1.45 min-1 when incubated in 16.5 mM glucose), because the insulin release with encapsulated islets was 1.42 +/- 0.49 compared to 13.58 +/- 0.80 with free control islets. This could not be explained by inadequate permeability of the capsule, because insulin release was also severely reduced (2.12 +/- 0.61) when islets were subjected to the procedure but without the membrane-forming polylysine step. Therefore, islets were tested after having been subjected separately to each of the steps of the procedure. Insulin release was not affected by either alginate or CaCl2 but was severely reduced after prolonged suspension in saline or treatment with citrate. When saline and citrate were replaced by Ca2(+)-free Krebs-Ringer bicarbonate buffer (KRBB) and 1 mM EGTA, respectively, insulin release improved significantly both with complete and with incomplete (no polylysine step) encapsulation. This outcome was verified in a set of experiments run in parallel with islets derived from the same isolation procedure. Insulin release was 1.20 +/- 0.23 from islets encapsulated with the method of Lim and 10.73 +/- 1.04 from free control islets. With the modified procedure, insulin release was 9.17 +/- 0.52 vs. 9.61 +/- 1.27 for complete versus incomplete encapsulation, respectively. We conclude that Ca2(+)-free KRBB instead of saline and EGTA instead of citrate should be used to obtain an adequate insulin response from encapsulated islets and that the capsule membrane as such has no influence on glucose and insulin diffusion.

A versatile alginate droplet generator applicable for microencapsulation of pancreatic islets.

Alginate beads for immunoisolation of pancreatic islets by microencapsulation should be small, smooth, and spherical in order to ensure that around the islets a strong alginate-polylysine-alginate capsule will be formed with optimal biocompatibility and diffusion of nutrients and hormones. However, the preparation of small capsules around islets is difficult. Our newly designed air jet droplet generator allows for variations in the length and diameter of the alginate nozzle and the air jacket and is in this way adaptable to a required bead size. Alginate droplets are converted into rigid beads in a 100 mM CaCl 2 solution. Their size depends upon the diameter of the jacket, the air flow rate, and the outer diameter of the nozzle, whereas the production rate depends upon the pressure on the alginate, and on the diameter and the length of the nozzle. When the air flow or the alginate flow surpasses a certain rate, the droplets are fragmented. This study describes the mutual relationship of these variables and defines their optimal range for reproducible production of smooth and spherical beads for microencapsulation of islets at an acceptable production rate.

Primary cardiac tumors.

From 1970 to 1986, 3 males and 6 females, ranging in age from 13 to 69 years (median 45 years), underwent heart surgery for a primary cardiac tumor. Six patients had a left atrial myxoma; a lipofibroma, a lymphosarcoma and a rhabdomyosarcoma were found each in 1 patient. The following complaints were present: congestive heart failure in 8, fatigue in 7, cardiac arrhythmia in 3, palpitations in 3, fever in 2 and finally weight loss, nocturnal perspiration and clubbing were each in one patient. The duration of symptoms ranged from 6 weeks to more than 2 years (median 10.8 months). All patients were operated with the aid of extracorporeal circulation as soon as they were diagnosed. One patient with extensive tumor growth died at the end of the procedure. During the follow-up period all patients with a primary malignant tumor died within 3 months. Those with myxoma or fibroma are still alive with a follow-up period extending to 13 years (median 7 years). All surviving patients are asymptomatic and well. Malignant cardiac tumors do have a very poor prognosis, they are only amenable for palliative resection and even then prognosis remains poor. When an endocardial biopsy confirms the diagnosis of a cardiac malignancy, the indication for operation is questionable, although there is an absolute indication in case of obstruction. Cardiac myxoma should be resected after diagnosis because the potential embolic complications may be debilitating or lethal. The operative risk is small, and the long term results are excellent.