Balloon sclerotherapy: a new method for the treatment of truncal varicose veins.

BACKGROUND: Truncal varicose veins may be treated by conventional surgery or endovenous therapy. Endovenous ablation, such as laser or radiofrequency treatment, is less invasive but technically demanding, not cheap and has still the possibility of important side-effects. Moreover the treatment requires in the best case tumescent anesthesia. Catheter based endovenous sclerotherapy has the potential of systemic effects of sclerosing agent and air. We therefore aimed to develop a simple, minimal-invasive and cheap method for the treatment of truncal varicose veins reducing the potential risk of systemic effects of the sclerosing agent to a minimum. METHODS: A double lumen double balloon catheter was developed. Thereby a treatment site within a vein can be isolated from blood for localized administration of a sclerotherapeutic agent. Later, a substantial portion of the therapeutic agent can be removed from the isolated segment thus minimizing the amount necessary. Occlusion of longer varicose segments is achieved by pointwise repetition of the manoeuvre or careful retraction of the expanded balloons with the "catched" sclerotherapeutic agent in between. RESULTS: The application was filed as United States Patent No. 6,726,67 B2. 18 balloon prototypes successfully passed an extensive test series (leak tests, dimension tests, mandrel--, guide wire--and introducer compatibility tests, destructive tests). Three patients with varicosity of the greater saphenous vein and the vena saphena accessoria lateralis, respectively, were successfully treated with complete occlusion of the vessels 10, 6 and 2 months after the intervention. CONCLUSIONS: Balloonsclerotherapy combines two well-established procedures (balloon catheter therapy and sclerotherapy, namely) and promises to be a minimal-invasive and cheap endovenous therapy of truncal varicose veins, requiring local anesthesia at the puncture site only and reducing possible systemic side effects of the sclerosing agent.

Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation.

Despite a clinically recognized association between the lymphatics and metastasis, the biology of tumor-lymphatic interaction is not clearly understood. We report here that functional lymphatic capillaries are absent from the interior of a solid tumor, despite the presence within the tumor of the lymphangiogenic molecule vascular endothelial growth factor (VEGF)-C and endothelial cells bearing its receptor, VEGF receptor 3. Functional lymphatics, enlarged and VEGF receptor 3 positive, were detected in some tumors only at the tumor periphery (within 100 microm of the interface with normal tissue). We conclude that although lymphangiogenic factors are present, formation of functional lymphatic vessels is prevented, possibly due to collapse by the solid stress exerted by growing cancer cells.

Alveolar echinococcosis of the liver: sequelae of chronic inferior vena cava obstructions in the hepatic segment.

BACKGROUND: The clinical pattern and long-term course of chronic inferior vena cava (IVC) obstructions are variable and depend on the underlying cause, the segment involved, and the extension of secondary thrombosis. Pertinent data on IVC obstructions in well-defined series of patients are lacking. We report the sequelae of chronic IVC obstructions in the hepatic segment in 11 consecutive patients derived from a cohort of 104 patients with alveolar echinococcosis of the liver. METHODS: Based on the results of computed tomography scans, 11 patients (7 men, 4 women; mean age, 53.4 years) with IVC obstructions were selected from an ongoing prospective long-term chemotherapy trial comprising 104 patients with alveolar echinococcosis studied at yearly intervals according to a protocol. Obstruction of the IVC in the 11 patients existed for a mean duration of 8.6 years. In these patients, magnetic resonance imaging was performed to assess the morphologic features and extension of the IVC obstruction, as well as the collateral venous pathways. Patency and valvular function of the femoropopliteal veins were analyzed by color-coded duplex ultrasonography. RESULTS: Total occlusions of the IVC were evident in 8 patients (73%) and subtotal stenoses in 3 patients (27%). Only 4 patients (36%) exhibited signs and symptoms of chronic venous insufficiency of the lower extremities; 2 (18%) of the 4 had a history of swelling in the lower extremity. Seven patients (64%) had no lower extremity symptoms. One patient had a history of pulmonary embolism. Abdominal collateral veins were documented in 5 patients (45%) by using magnetic resonance imaging; however, they were clinically evident in only 3 patients (27%). In the 8 patients with IVC occlusion, thrombosis ended at the confluence of the hepatic veins. Obstruction of the IVC was limited to the hepatic segment in 2 patients (18%) and extended to the distal IVC or the iliofemoral veins in 6 patients (54%). Chronic venous insufficiency was present only if the femoropopliteal veins had been involved in the thrombotic process, showing residual venous obstruction, valvular incompetence, or both. Bilateral renal vein thrombosis with moderate proteinuria was observed in 2 patients (18%). The main collateral drainage was achieved through the ascending lumbar, azygos, and hemiazygos veins. CONCLUSIONS: In patients with alveolar echinococcosis, obstruction of the IVC in the hepatic segment often develops asymptomatically and rarely leads to the impairment of renal function. The collateral circulation fully compensates for obstruction of the IVC. Thrombotic involvement and valvular incompetence of the femoropopliteal veins seems to determine the development of chronic venous insufficiency of the lower extremities.

Phlebosclerosis, phlebothrombosis, and thrombophlebitis: A current perspective.

Phlebosclerosis, phlebothrombosis, and thrombophlebitis are three fundamentally different structural changes affecting superficial, deep, visceral, and cerebral veins. Phlebosclerosis is a frequent, age-dependent fibrotic degeneration of one or all three wall layers. It does not represent a distinct disease entity but may impair the venous function and contribute to the development of thrombosis. Phlebothrombosis represents a serious circulatory disorder. It may be due to a variety of factors including phlebitis, i.e., a primary inflammatory disease of the venous wall. Thrombophlebitis may be a relatively harmless disorder, such as represented by idiopathic skipping phlebitis (phlebitis saltans), or it may be a symptom of an underlying systemic disease. Whereas phlebothrombosis in nonvaricose veins is suspicious of an underlying malignancy or a coagulation disorder, thrombophlebitis is not related to malignancies but may accompany Buerger's disease or other systemic vasculitides. The histopathological distinction of phlebothrombosis and thrombophlebitis is therefore of paramount importance and determines further clinical investigations. A proposal for classification of thrombophlebitides and some guidelines for clinicopathological differentiation of the various types of phlebitides are presented.

Fluorescence microlymphography of the upper extremities. Evaluation with a new computer programme.

BACKGROUND: To evaluate the initial lymphatics of the superficial skin in healthy volunteers using fluorescence microlymphography and to establish controls values for comparison with lymphedema patients. METHODS: Fluorescence microlymphography was performed on the hand dorsum, on the lower and the upper arm in 12 healthy subjects (58.7+/-8.0 years). At each of these sites 10 microl FITC-dextran was injected subepidermally using a steel cannula. The studies were recorded on video tape using a fluorescence microscope and a CCD video camera. Final magnification was 24 and 62. The maximum spread of the fluorescent contrast medium was measured 10 minutes after injection. The area of the visualized lymph capillaries was determined using a computer programme. SETTING: University Hospital, Department of Medicine, Division of Vascular Medicine (Angiology). RESULTS: The mean area of the visualised lymph capillary network 95.3+/-41.3 mm2 (42-174 mm) at the upper and 89.4+/-45.5 mm2 (44-171 mm). The maximum spread was 4.8+/-3.5 mm (1.9-13.6 mm) and 4.4+/-3.7 mm, respectively. The mean diameter of the lymph capillaries was 84.1+/-19.9 microm and 75.5+/-14.8 microm, respectively. CONCLUSIONS: The extension of the lymph capillary network at the upper and lower arm are comparable to those at the lower extremities. Considering the two-dimensional nature and the irregular shape of the network the area measurement seems to be more appropriate than the maximum spread in one direction.

Long-term results of percutaneous thrombo-embolectomy in patients with infrainguinal embolic occlusions.

BACKGROUND: The aim of the study was to review early and long term clinical results of percutaneous thrombo-embolectomy in patients with acute embolic occlusions of the infrainguinal arteries. METHODS: Retrospective analysis of consecutive cases. A total of 88 procedures in 84 patients were performed between 1986 and 1996 in a University Hospital (46 men, 42 women; mean age 67.6 +/- 14.4 years). Patients with a history of chronic symptomatic arterial occlusive disease were not included in the analysis. Indications for treatment were severe claudication (n = 45 procedures) and limb threatening ischaemia (n = 43 procedures). Percutaneous thrombo-embolectomy was performed via an ipsilateral approach by means of an end hole aspiration catheter. Local thrombolysis or balloon angioplasty was used as appropriate during the intervention. Follow-up included clinical data, ankle pressure measurements, pulse volume recordings and duplex sonography or angiography if indicated. RESULTS: Technical success was achieved in 85 (96.6%) of the 88 procedures. Two patients (2.3%) suffered major and two patients (2.3%) minor complications. One patient died within 30 days after the procedure. Mean follow-up was 3.7 +/- 2.9 years. Twelve patients (16%) were lost to follow-up. Primary clinical success rate was 88.4% at one and 81.7% at two years and declined to 76.5% at eight years. Out of the 16 interval failures 10 (63%) were due to recurrent embolism to the same leg. They resulted in nine catheter reinterventions and one bypass graft. Six patients were treated conservatively. Cumulative mortality was 11.7% at one year and increased to 29.5% at eight years. CONCLUSIONS: From our single centre experience we conclude that catheter treatment of acute embolic occlusion of infrainguinal arteries is safe and has favourable long-term RESULTS. We therefore regard the technique as a less invasive alternative to surgery.

Microvascular changes in venous disease: an update.

In an overview the microvascular involvement in chronic venous insufficiency (CVI) is described. Microangiopathy in the lower leg areas is characterized by the presence of typical enlarged and ramified blood capillaries, reduced capillary number, microvascular thrombosis and obliterations, and/or increased permeability of microlymphatics. Transcutaneous oxygen tension (tcPO2) is decreased and directly correlated to the number of perfused capillaries, whereas laser Doppler flux is enhanced. This apparent paradox may be explained by hyperperfusion in the deeper skin layers (mainly shunt vessels) and hypoperfusion in the superficial nutritive vessels. Microvascular changes are of patchy distribution. Trophic changes up to overt venous ulceration are mainly caused by microvascular ischemia and edema formation due to increased capillary permeability and deficient lymphatic drainage.

[Discomfort in the leg--differential edema/pain diagnosis of the lower extremities]. / Pein im Bein--Differentialdiagnose von Odem/Schmerzen der unteren Extremitäten.

Pain and/or edema are a frequent complaint of ambulatory patients. Differential diagnosis may be difficult and must consider a wide spectrum of vascular and non-vascular disorders. A systematic overview of the most frequent underlying disorders with two tables is presented. Such tables may be helpful but it must be kept in mind that the symptoms may be varying and/or overlapping. The additional explanations point out some of the most frequent pitfalls.

Evidence for microvascular thrombosis obtained by intravital fluorescence videomicroscopy.

A pattern of enlarged capillaries densely packed with red cells and not filled by the intravital dye Na-fluorescein for 10-20 min is described. Probably it corresponds to microvascular thrombosis. Alternative explanations like prolonged stasis appear unlikely. Up to now the pattern has been detected in severe chronic venous incompetence, collagen vascular disease and essential thrombocytosis.

[Biopsy in systemic vasculitis: guidelines and risks]. / Die Biopsie bei systemischen Vaskulitiden: Richtlinien und Fallstricke.

Biopsy examinations may be of great importance for the diagnosis of systemic vasculitides if they are correctly performed and some general pitfalls are avoided. Apart from technical mistakes (insufficient or too superficially excised material, necrotic tissue material without intact border areas, bad or retarded fixation), the following points should be kept in mind: Immunohistochemical and electron microscopic examinations are practically worthless for diagnostic reasons. The surgical access to the biopsy area and the tolerability of the intervention should be carefully evaluated. Biopsies without sufficient information to the pathologist about the clinical findings and the laboratory results are often responsible for insufficient pathology reports. Biopsies during or immediately after a corticosteroid treatment provide faulty results. Skin biopsies in systemic vasculitides usually present non-specific alterations. Polymyalgia does not cause a temporal arteritis and no conclusive findings within the striated musculature. A "blind" temporal artery biopsy has only a limited chance to provide findings of diagnostic value. The sites which offer the best possibilities for biopsy in various systemic vasculitides are enumerated and the possible histology findings at these sites are discussed.

Dose-dependent increase of transcapillary diffusion of sodium fluorescein after histamine microinjections.

BACKGROUND: To study the dose-dependent effects of histamine on capillary permeability in human skin, using the microinjection technique. PATIENTS AND METHODS: Eight healthy volunteers (2 w, 6 m; mean age 33 years) were included in the study. On two separate occasions, glass microcannulas with a tip diameter of 7 to 9 microns were inserted into the subepidermal layer of the skin at the distal medial tibia surface of each lower limb with a micromanipulator. In each subject, 0.5 microliter of 3 different concentrations of histamine solution (0.1/1000, 0.01/1000 and 0.001/1000) were injected and compared to the solvent (0.9% NaCl). Transcapillary diffusion of intravenously administered Na-fluorescein was assessed simultaneously using two fluorescence videomicroscopy systems. Off-line video densitometry was performed in an area of 0.56 mm2 around the injection sites and fluorescence light intensities were measured in arbitrary units (AU) at 10, 30, 60, 120 and 600 s after dye appearance. RESULTS: Compared to the solvent histamine microinjections resulted in a dose-dependent increase of mean fluorescence light intensities (FLI). Whereas mean FLI for the 0.001/1000 histamine injection was only significantly elevated 10 min after dye appearance (p < 0.05) an increase of mean FLI was already observed 10 s after dye appearance following the 0.1/1000 histamine injection (p < 0.05), which was more pronounced at later time points (p < 0.001). Mean FLI's for the 0.01/1000 histamine solution were in between and resulted in significantly elevated values 1 min to 10 min after dye appearance (p < 0.05). CONCLUSIONS: We conclude that the microinjection technique together with fluorescence videomicroscopy described previously [6] is able to document a dose-dependent effect of histamine microinjections on skin capillary permeability. The technique may facilitate to determine appropriate dosages not only of histamine in order to test the effect of antagonists on human skin capillary permeability.

Spontaneous reversibility of early reobstruction following percutaneous transluminal angioplasty.

Early reocclusion and late restenosis are well-known problems after percutaneous transluminal angioplasty (PTA). We report here on a phenomenon not described so far in two patients with peripheral arterial occlusive disease who had PTA of the common iliac and the superficial femoral artery, respectively. Both had a good hemodynamic and clinical initial result. However, within two days after PTA symptomatic reobstruction occurred documented by noninvasive measurements. Noteworthy, this reobstruction was spontaneously reversible within days. The possible pathomechanism is discussed.

[Microangiopathies in chronic venous insufficiency (CVI)]. / Mikroangiopathie bei chronisch-venöser Insuffizienz (CVI).

The degree of cutaneous microangiopathy at the medial ankle correlates with the severity of chronic venous insufficiency, most probably it is the trigger factor for development of trophic skin lesions. Using intravital fluorescence videomicroscopy, microlymphography, transcutaneous oxygen tension measurement and laser Doppler flowmetry, the microangiopathy is characterized by morphological alterations of blood and lymph capillaries and by dynamic changes (decreased transcutaneous oxygen tension reflecting microvascular ischemia, increased skin perfusion). Microangiopathy in patients with chronic venous insufficiency is recognized by the presence of dilated, elongated and tortuous (glomerulus-like) capillaries and by an increase in diameter of the pericapillary space (halo) filled by Na-fluorescein. In severe CVI a reduction of the capillary number can be observed, probably as a result of previous capillary thrombosis. Lymphatic drainage is disturbed and lymph capillaries are obliterated in part. Laser Doppler flowmetry, which detects flux in deeper, non-nutrient skin vessels, shows increased blood flow. However, the postural vasoconstrictive response remains intact and there is little alteration in the spontaneous rhythmic flux waves. In contrast to deeper skin flux transcutaneous oxygen tension is reduced, in keeping with the microangiopathy observed in the superficial nutrient capillaries. These pronounced morphological and dynamic changes explain the development of trophic skin lesions.

[Hyperbilirubinemia]. / Hyperbilirubinämie.

A 22-year-old woman had icteric sclerae since childhood. Five years ago of Gilbert-Meulengracht's disease was diagnosed (hyperbilirubinemia, normal other liver laboratory parameters, no evidence of hemolysis). The patient was admitted for re-evaluation. Apart from jaundice of the sclerae no other clinical symptoms were found. Analysis of urine revealed bilirubin and an increased urobilinogen. Serum bilirubin was also elevated. The differentiation of the bilirubin gave evidence of an increase of the direct (conjugated) bilirubin portion. Additional investigations (total coproporphyrin in the urine, isomer I and isomer III coproporphyrin excretion and bromsulphalein test) suggested Rotor's syndrome. Further examinations (oral cholecystography, liver biopsy) were not added because of relative invasiveness, lack of clinical consequences and opposition of the patient. Nevertheless the diagnosis of a Rotor's syndrome is highly probable.

[Clubbed fingers, hourglass nails]. / Trommelschlegelfinger, Uhrglasnägel.

Clubbing was the main clinical symptom in a 27 year old male patient. There was no clubbing in other family members. Secondary clubbing was excluded by clinical findings, laboratory, x-ray of the chest, electrocardiography, pulmonary function test, blood gas analysis, colonoscopy, x-ray of hands and feet and capillary microscopy. Final diagnosis was idiopathic clubbing.

[Secondary prevention of arteriosclerosis]. / Sekundärprävention der Arteriosklerose.

Secondary prevention of arteriosclerosis tries to inhibit progression of the atherosclerotic process. Therapeutic measures focus on modification of cardiovascular risk factors and antithrombotic treatment. Hypercholesterolemia is the main risk factor for coronary artery disease. The risk of a coronary event is correlated to the plasma cholesterol level. Lowering plasma cholesterol results in reduction of vascular morbidity and mortality. Cigarette smoking is the predominant risk factor for peripheral arterial occlusive disease (PAOD). Smoking cessation reduces progression of PAOD and lowers cardiovascular morbidity and mortality. The preventive effect of antihypertensive therapy in hypertensive patients is most pronounced for cerebrovascular events. Antihypertensive measures improve prognosis after stroke and myocardial infarction. The increased cardiovascular risk in diabetics is in part explained by hyperglycemia and hyperinsulinemia, but also depends on coexisting dyslipidemia and hypertension. Intensive treatment of elevated blood glucose levels, dyslipidemia and hypertension are important preventive measures. Aspirin is highly effective in secondary prevention of vascular events. For the coronary arteries, low-dose aspirin is well established. Whether low-dose aspirin is equally effective for reducing progression of arteriosclerosis in the cerebrovascular and in the peripheral vessels is questionable. Ticlopidine serves as an alternative to aspirin; however, neutropenia may occur, which requires supervision of the patient.

Effect of venous and lymphatic congestion on lymph capillary pressure of the skin in healthy volunteers and patients with lymph edema.

The aim of the present study was to assess the influence of venous and lymphatic congestion on lymph capillary pressure (LCP) in the skin of the foot dorsum of healthy volunteers and of patients with lymph edema. LCP was measured at the foot dorsum of 12 patients with lymph edema and 18 healthy volunteers using the servo-nulling technique. Glass micropipettes (7-9 microm) were inserted under microscopic control into lymphatic microvessels visualized by fluorescence microlymphography before and during venous congestion. Venous and lymphatic congestion was attained by cuff compression (50 mm Hg) at the thigh level. Simultaneously, the capillary filtration rate was measured using strain gauge plethysmography. The mean LCP in patients with lymph edema increased significantly (p < 0.05) during congestion (15.7 +/- 8.8 mm Hg) compared to the control value (12.2 +/- 8.9 mm Hg). The corresponding values of LCP in healthy volunteers were 4.3 +/- 2.6 mm Hg during congestion and 2.6 +/- 2.8 mm Hg during control conditions (p < 0.01). The mean increase in LCP in patients with lymph edema was 3.4 +/- 4.1 mm Hg, and 1.7 +/- 2.0 mm Hg in healthy volunteers (NS). The maximum spread of the lymph capillary network in patients increased from 13.9 +/- 6.8 mm before congestion to 18.8 +/- 8.2 mm during thigh compression (p < 0.05). No increase could be observed in healthy subjects. In summary, venous and lymphatic congestion by cuff compression at the thigh level results in a significant increase in LCP in healthy volunteers as well as in patients with lymph edema. The increased spread of the contrast medium in the superficial microlymphatics in lymph edema patients indicates a compensatory mechanism for lymphatic drainage during congestion of the veins and lymph collectors of the leg.

Severe potential consequences of delayed diagnosis in patients with hip claudication.

Delayed diagnosis in patients with hip claudication can lead to severe consequences. We report on patients with ischaemic hip claudication which had primarily been attributed to coxarthrosis. One patient went through a variety of treatments including hip arthroplasty. The second patient had a life-threatening abdominal aortic aneurysm (AAA) which remained undiagnosed. Orthopaedic surgeons should maintain a high degree of suspicion for vascular disease. Moreover, we strongly advocate that all men over 60 years old who seek medical advice for whatever reason should be screened once for AAA by ultrasonography.