Core content for venous and Lymphatic Medicine: 2022 revision.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

Regulation of matrix contraction in chronic venous disease.

OBJECTIVE: The role of TGF-beta(1) in venous ulcer healing and the signalling cascades regulating dermal fibroblast function are poorly understood. To elucidate these processes, we hypothesized that TGF-beta(1) facilitates wound healing by increasing chronic venous insufficiency (CVI) induced matrix contraction via intracellular cross-talk between TGF-beta(1) and the ERK-1/2 MAP kinase signalling cascades. METHODS: Fibroblasts isolated from calf biopsies (LC) of patients with different severity of CVI (CEAP, Clinical Etiological Anatomical Pathological classes) were seeded into 200 microl collagen gels under isometric conditions. Fibroblasts from neonatal foreskins (HS68), non-CVI patients (NC), and the ipsilateral normal thigh of each CVI patient (LT) served as controls. Thirteen patients with CVI (class 2, n=5; class 4, n=5; class 6, n=3) and 2 non-CVI controls (NC, n=2) were included in the study. All experimental conditions were determined by dose-response and time-course experiments. Gels were cultured with/without 0.1 ng/ml TGF-beta(1) and with/without 50 microM PD98059 (MEK and downstream-MAPK inhibitor). Additional patient fibroblasts were transfected with constitutively active Ras (pCMV-Ras) or an empty vector (pCMV-beta) with/without 0.1 ng/ml TGF-beta(1) and with/without 50 microm PD98059. The collagen gels were released after 4 days and the percent contraction was determined by area measurements using image analysis. Differences in alpha-smooth muscle actin (alpha-SMA) and ERK-1/2 MAPK (phosphorylated and total) protein levels were analyzed with western blotting. RESULTS: Gels seeded with CVI fibroblasts contracted more than HS68, NC and LT fibroblasts. Inhibition of MAPK and/or stimulation with TGF-beta(1) increased the contraction of LC gels compared to unstimulated controls. Agonist induced gel contraction correlated with CVI disease severity. alpha-SMA protein expression in LC fibroblasts increased with MAPK inhibition with/without TGF-beta(1) stimulation, and correlated with the degree of gel contraction. Transfection with pCMV-Ras (activator of ERK-1/2) inhibited gel contraction; this inhibition was not reversed by addition of TGF-beta(1). Transfection with the pCMV-beta empty vector had no effect on gel contraction. CONCLUSIONS: TGF-beta1 stimulation of CVI patient fibroblasts grown in 3D collagen gels results in conversion to a contractile phenotype through upregulation of alpha-SMA, and in enhanced gel contraction. Inhibition of MAPK further increases gel contraction, while Ras activation of ERK-1/2 inhibits TGF-beta1-induced gel contraction. These responses correlate with increasing CEAP severity. CVI fibroblast mediated gel contraction is therefore regulated through cross-talk between the ERK-1/2 MAPK and TGF-beta(1) signalling cascades. These data identify potentially clinically relevant therapeutic molecular targets that could enhance matrix contraction and thereby improve venous ulcer wound healing.

Role of matrix metalloproteinases 1, 2, and 9 and tissue inhibitor of matrix metalloproteinase-1 in chronic venous insufficiency.

PURPOSE: Increased transforming growth factor-beta(1) (TGF-beta(1)) activity is associated with chronic venous insufficiency (CVI) disease progression and dermal skin pathology. Because TGF-beta(1) stimulates collagen synthesis and alters the levels of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), we investigated the hypothesis that increased TGF-beta(1) activity is associated with differences in messenger RNA and protein levels of MMPs and TIMP-1 in patients with CVI. METHODS: One hundred ten biopsies of the lower calf and lower thigh in 73 patients were snap frozen in liquid nitrogen and stratified into six groups according to the clinical etiologic anatomic distribution pathophysiology disease classification. One set of lower-calf and lower-thigh biopsies were analyzed for MMP-1 and TIMP-1 gene expression with quantitative reverse transcription and competitive polymerase chain reaction. A second set of biopsies was analyzed for the active and latent forms of MMP-1, MMP-2, and MMP-9 as well as for TIMP-1 by western blotting, gelatin zymography, and tissue localization by immunohistochemistry (IHC). RESULTS: Compared with the control, MMP-1 messenger RNA was increased in class-4 and class-6 patients (P < or =.01), whereas TIMP-1 was increased in class-6 patients only (P < or =.05). However, there were no differences in total protein between MMP-1 and TIMP-1. Active MMP-2 protein increased in class-4 and class-5 patients compared with active MMP-1 and TIMP-1 (P < or =.01). Western blotting did not identify the active component of MMP-9. Similarly, only the latent form of MMP-9 was observed by gelatin zymography, whereas both the latent and active forms of MMP-2 were observed. IHC demonstrated MMP-1 and MMP-2 in dermal fibroblasts and in perivascular leukocytes. TIMP-1 was observed in basal-layer keratinocytes of the epidermis only. MMP-9 was not detected by IHC. CONCLUSION: MMP synthesis is regulated at both the transcriptional and post-transcriptional levels in CVI. Our data suggest that post-translational modifications are key to functional regulation. Dermal fibroblasts and migrating leukocytes are probable cellular sources of MMPs. Increased active MMP-2 levels in class-4 and class-5 patients indicate tissue remodeling caused by pre-ulcer and postulcer environmental stimuli. These data suggest that alterations in MMP-2 activity, in conjunction with TGF-beta(1)-mediated events, cause an imbalance in tissue remodeling leading to a pro-ulcer-forming environment.

VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways.

VEGF is a key regulator of vascular permeability. However, its signaling pathways are incompletely understood. We tested the hypothesis that VEGF regulates endothelial cell (EC) permeability by activating PKB/akt, NOS, and MAP kinase dependent pathways using human umbilical vein EC (HUVEC). Permeability was measured from FITC-dextran 70-kDa flux across the EC monolayer at baseline and after VEGF at 0.034, 0.068, 1, 10, and 100 nM. VEGF increased HUVEC permeability to FITC-dextran in a dose-dependent manner. VEGF (1 nM) increased permeability from 3.9 x 10(-6) +/- 0.7 x 10(-6) to 14.0 x 10(-6) +/- 1.7 x 10(-6) cm/s (mean +/- SEM; P < 0.001). Permeability changes were also assessed after treatment with 1, 10, and 100 nM wortmannin (PI 3-kinase inhibitor); 0.01, 0.1, and 1.0 nM LY294002 (PI 3-kinase inhibitor); 200 microM l-NMMA (NOS inhibitor); 2.7 microM AG126 (p42/44(MAPK) inhibitor); and 0.006, 0.06, and 0.6 microM SB203580 (p38(MAPK) inhibitor). All inhibitors blocked VEGF-induced permeability changes. Our data demonstrate that (1) VEGF increases permeability of EC monolayers in a dose-dependent fashion, and (2) VEGF-induced permeability is mediated through PI-3 kinase-PKB, NOS, and MAP-kinase signaling cascades. These observations suggest that microvascular hyperpermeability associated with inflammation and vascular disease is mediated by activation of these EC signaling pathways.

In-stent restenosis after carotid angioplasty-stenting: incidence and management.

PURPOSE: Carotid angioplasty-stenting (CAS) has been advocated as an alternative to carotid endarterectomy (CEA) in patients with restenotic lesions after prior CEA, primary stenoses with significant medical comorbidities, and radiation-induced stenoses. The incidence of restenosis after CAS and its management remains ill defined. We evaluated the incidence and management of in-stent restenosis after CAS. METHODS: Patients with asymptomatic (61%) and symptomatic (39%) carotid stenosis of > or = 80% underwent CAS between September 1996 and May 2000; there were 50 procedures and 46 patients (26 men and 20 women). All patients were followed up clinically and underwent duplex ultrasonography (DU) at 3- to 6-month intervals. In-stent restenoses > or = 80% detected with DU were further evaluated by means of angiography for confirmation of the severity of stenosis. RESULTS: No periprocedural or late strokes occurred in the 50 CAS procedures during the 30-day follow-up period. One death (2.2%) that resulted from myocardial infarction was observed 10 days after discharge following CAS. During a mean follow-up period of 18 +/- 10 months (range, 1-44 months), in-stent restenosis was observed after four (8%) of the 50 CAS procedures. Angiography confirmed these high-grade (> or = 80%) in-stent restenoses, which were successfully treated with balloon angioplasty (3) or angioplasty and restenting (1). No periprocedural complications occurred, and these patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 +/- 6 months. CONCLUSIONS: We recommend CAS for post-CEA restenosis, primary stenoses in patients with high-risk medical comorbidities, and radiation-induced stenoses. In-stent restenoses occurred after 8% of CAS procedures and were managed without complications with repeat angioplasty or repeat angioplasty and restenting.

Vein interposition cuffs decrease the intimal hyperplastic response of polytetrafluoroethylene bypass grafts.

PURPOSE: The modification of the distal anastomosis of polytetrafluoroethylene (PTFE) bypass grafts with vein interposition cuffs (VCs) has been reported to increase graft patency. However, the mechanisms that are responsible for this improved patency are unclear. Because intimal hyperplasia (IH) is a primary cause of prosthetic graft failure, we hypothesized that VCs affect the distal anastomosis by decreasing the IH response of the outflow artery. METHODS: Twenty-three female domestic Yorkshire pigs (mean weight, 35 kg) underwent 42 femoral PTFE bypass grafting procedures. The PTFE bypass grafts were separated into the following three groups according to distal anastomotic configuration: end-to-side anastomoses (ES), VCs, and cuffs constructed with PTFE (PCs). Four femoral arteries from two pigs served as healthy controls. At sacrifice, the grafts were perfusion fixed, and the distal anastomoses harvested at 1 and 4 weeks. The specimens were hemisected and serially sectioned to identify the heel, toe, and mid-anastomotic regions. The sections were cut into 5-microm segments and analyzed for intima and media thickness and area, intima/media area ratio, and the distribution of IH in the vein cuff. The roles of transforming growth factor-beta1 and platelet-derived growth factor-BB in IH development were assessed with immunohistochemistry. RESULTS: IH development was significantly lower at all areas of the anastomosis, with VCs compared with ES and PCs at 4 weeks (P

Microcirculatory inflammation in chronic venous insufficiency: current status and future directions.

One of the hallmarks of chronic venous insufficiency (CVI) is an elevated venous pressure. However, no direct link at the cellular and molecular levels between venous hypertension and actual tissue damage in CVI has been established. Evidence for generations of an inflammatory reaction and several molecular alterations in the development of CVI is discussed. Development of experimental models of CVI, analysis of the mechanical tissue stresses in addition to venous hypertension, in combination with systematic studies of clinically stratified and standardized patient-derived samples is required for molecular description of the pathogenesis of CVI.

Mandibular subluxation for distal internal carotid exposure: technical considerations.

PURPOSE: Carotid endarterectomy (CEA) has become one of the most commonly performed vascular procedures, because of the beneficial outcome it has when compared with medical therapy alone and because of the anatomic accessibility of the artery. In cases of distal carotid occlusive disease, high cervical carotid bifurcation, and some reoperative cases, access to the distal internal carotid artery may limit surgical exposure and increase the incidence of cranial nerve palsies. Mandibular subluxation (MS) is recommended to provide additional space in a critically small operative field. We report our experience to determine and illustrate a preferred method of MS. METHODS: Techniques for MS were selected based on the presence or absence of adequate dental stability and periodontal disease. All patients received general anesthesia with nasotracheal intubation before subluxation. Illustrations are provided to emphasize technical considerations in performing MS in 10 patients (nine men and one woman) who required MS as an adjunct to CEA (less than 1% of primary CEAs). Patients were symptomatic (n = 7) or asymptomatic (n = 3) and had high-grade stenoses demonstrated by means of preoperative arteriography. RESULTS: Subluxation was performed and stabilization was maintained by means of: Ivy loop/circumdental wiring of mandibular and maxillary bicuspids/cuspids (n = 7); Steinmann pins with wiring (n = 1); mandibular/maxillary arch bar wiring (n = 1); and superior circumdental to circummandibular wires (n = 1). MS was not associated with mandibular dislocation in any patient. No postoperative cranial nerve palsies were observed. Three patients experienced transient temporomandibular joint discomfort, which improved spontaneously within 2 weeks. CONCLUSION: Surgical exposure of the distal internal carotid artery is enhanced with MS and nasotracheal intubation. We recommend Ivy loop/circumdental wiring as the preferred method for MS. Alternative methods are used when poor dental health is observed.

Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production.

PURPOSE: Pathologic dermal degeneration in patients with chronic venous insufficiency (CVI) is characterized by aberrant tissue remodeling that results in stasis dermatitis, tissue fibrosis, and ulcer formation. The cytochemical processes that regulate these events are unclear. Because transforming growth factor-beta(1) (TGF-beta(1)) is a known fibrogenic cytokine, we hypothesized that the increased production of TGF-beta(1) would be associated with CVI disease progression. METHODS: Seventy-eight punch biopsy specimens of the lower calf (LC) and the lower thigh (LT) of 52 patients were snap frozen in liquid nitrogen and stratified into four groups according to the Society for Vascular Surgery/International Society for Cardiovascular Surgery CEAP classification (C, clinical; E, etiologic; A, anatomic distribution; and P, pathophysiology). One set of LC biopsy specimens were analyzed for TGF-beta(1) gene expression with quantitative reverse transcriptase-polymerase chain reaction: healthy skin, n = 6; class 4, n = 6; class 5, n = 5; and class 6, n = 7. A second set of biopsy specimens from the LC and LT were analyzed for the amount of bioactive TGF-beta(1) with a certified cell line 64 mink lung epithelial bioassay: healthy skin, n = 8; class 4, n = 23; class 5, n = 13; and class 6, n = 10. The location of TGF-beta(1) was determined at the light and electron microscopy level with immunocytochemistry and immunogold (IMG) labeling. Multiple comparisons were analyzed with a one-way analysis of variance and the Student-Newman-Keuls post hoc tests. The LC and LT comparisons were analyzed with a two-tailed unpaired t test. RESULTS: The TGF-beta(1) gene transcripts for control subjects and patients in classes 4, 5, and 6 were 7.02 +/- 7.33, 43.33 +/- 9.0, 16.13 +/- 7.67, and 7.22 +/- 0.56 x 10(-14) mol/microg total RNA, respectively. The transcripts were significantly elevated in class 4 patients only (P

Sensory impairment: a feature of chronic venous insufficiency.

OBJECTIVE: Clinical and microscopic evidence suggests the existence of sensory neuropathy in patients with severe chronic venous insufficiency (CVI). A clinical evaluation was conducted to determine whether a sensory neuropathy was present and, if so, to determine its extent and distribution. METHODS: The study was performed in a university-affiliated Veterans Affairs Medical Center. Twenty-three limbs were studied in 14 male veterans with mild or moderate CVI. The exclusions included diabetes, previous ipsilateral extremity surgery, or other diseases associated with neuropathy. Sensory thresholds in the limbs with CEAP class 2 disease (n = 11) were compared with the thresholds in the limbs with CEAP class 5 disease (n = 12) at nine different sites on the foot, ankle, calf, thigh, and palm. Thenar and hypothenar thresholds were measured as internal controls. Thresholds were determined by a pressure aesthesiometer consisting of 20 graduated filaments that ranged from 1.65 to 6.65 (log(10)mg)(10) of pressure. A complete, sensory motor assessment of the limb was performed by an experienced neurosurgeon who specialized in peripheral nerve evaluation. The clinical variables assessed were deep tendon reflexes, vibration, proprioception, and light touch. Venous reflux was determined with duplex ultrasound scanning and air plethysmography. RESULTS: Sensory thresholds at the most common site of venous ulceration-just proximal to the medial malleolus--were significantly (P <.05) different between mild (class 2) and severe (class 5) CVI. Sensory abnormalities coincided with the extent of trophic changes and did not reflect specific dermatomal or cutaneous nerve distributions. In addition to light touch or pinprick, vibration sense and deep tendon reflexes were also significantly worse in those with severe CVI. CONCLUSION: Sensory neuropathy is a feature of severe CVI, and its distribution is coincident with trophic changes. Because this is often unappreciated by the patient, it probably contributes to the propensity for deterioration from minor trauma.

Aortic reconstruction in the HIV infected patient.

Major vascular reconstruction using prosthetic implantation is uncommon in the HIV infected patient. We describe a 52-year-old man with HIV infection and HIV-induced thrombocytopenia, who underwent successful aorto-bifemoral bypass for lower extremity ischemic symptoms. Postoperative progressive thrombocytopenia and subsequent hemorrhage were successfully treated with intravenous steroid replacement, platelet transfusion, alpha-globulin administration and expectant management. This report serves to illustrate that major vascular reconstruction can be successfully accomplished in the HIV infected population, even in the presence of significant hematologic dysfunction.

Patency and limb salvage for polytetrafluoroethylene bypasses with vein interposition cuffs.

Polytetrafluoroethelene (PTFE) is often utilized in patients with limb-threatening ischemia requiring infrainguinal revascularization in the absence of autologous saphenous vein. To increase long-term patency of PTFE grafts, vein interposition cuffs have been recommended as adjunctive procedures. The purpose of this study was to assess the efficacy of vein interposition cuffs on the long-term patency and limb salvage of patients requiring prosthetic bypass grafts for limb-threatening ischemia. Prosthetic bypass grafts with vein interposition cuffs (PTFE/VC) were performed on 56 limbs in 55 patients (32 men, 23 women; mean age of 67 years) from October 1993 to January 1998. Grafts were prospectively evaluated every 3 months for the first 12 months and biannually thereafter with duplex ultrasonography. PTFE/VC and PTFE bypasses at the popliteal level appear to have comparable patencies. However, PTFE/VC appear to offer an improved patency and limb salvage for infrapopliteal bypasses in patients with critical limb ischemia. When infrapopliteal revascularization is required in the absence of autologous saphenous vein, we recommend the use of PTFE with vein interposition cuffs.

Hemodialysis access: influence of the human immunodeficiency virus on patency and infection rates.

PURPOSE: The complication rate for patients who are dialysis dependent and infected with the human immunodeficiency virus (HIV) and the role of viral indicators (CD4 counts) as predictors of these complications are poorly characterized. To determine the influence of HIV status and viral activity on graft patency and infection rates, we retrospectively reviewed our results. METHODS: Between June 1993 and March 1997, the charts of 104 patients (HIV+, n = 42; HIV-, n = 62) who required 112 hemodialysis access grafts were reviewed. Of the 112 procedures, 55 (48%) were autologous arteriovenous fistulae (AVF) procedures (HIV+, n = 23; HIV-, n = 32) and 57 (52%) were prosthetic expanded polytetrafluoroethylene grafting procedures (HIV+, n = 27; HIV-, n = 30). Transcutaneous catheter procedures were excluded from the study. The autologous AVF procedures consisted of direct and transposed AVFs. Patency rates were determined by means of life-table analysis. Infection rates and CD4 counts were compared with the chi2 test and the Fisher exact test. Significance was accepted at a P value of.05 or less. RESULTS: The cumulative 12-month and 24-month patency rates for prosthetic grafts in patients who were HIV+ were 49% and 21%, respectively, versus 77% and 45% for patients who were HIV-. The differences in the prosthetic graft patency rates between these two groups were significant (P .05). The mean CD4+ cell counts were 174: CD4+ counts that were less than 200 did not correlate with or predict the development of infection (P >.05). CONCLUSION: Our data showed that prosthetic graft infection rates were increased and patency rates were decreased in patients who were HIV+ as compared with patients who were HIV- and HIV+ with autologous AVFs. There were no differences in patency rates or infection rates in patients who had undergone autologous access procedures. Long-term graft patency rates were not affected by HIV status, and CD4+ lymphocyte counts were not predictive of infection development. Because the prosthetic graft infection rates exceeded those rates of autologous access procedures, we recommend the vigorous use of autologous AVFs in all patients who are HIV+, regardless of CD4+ count.

Carotid restenosis: operative and endovascular management.

PURPOSE: Surgical management of carotid restenosis (CR) after carotid endarterectomy (CEA) has been associated with a higher perioperative complication rate than that of primary CEA. We recently used carotid angioplasty-stenting (CAS) as an alternative to operative management in patients who had undergone CEA within three years, and we retrospectively compared these results with those of operative management of CR and the overall results of CEA. METHODS: CEA was performed on 1065 adult patients (58% symptomatic, 42% asymptomatic), 62% of whom were men (n = 660) and 38% of whom were women (n = 405), from 1989 to 1997. Before our initiation of a program of CAS, 16 operative procedures (1.9% of CEAs) were performed for CR in 14 adult patients (7 women and 7 men). During the last 20 months, CAS was used in the management of 17 CRs (16 patients; 9 women and 7 men). RESULTS: The 30-day stroke morbidity-death rate for all CEAs (n = 1065) was 1.4%; 11 strokes (1. 0%) occurred (4 major strokes with disability and 7 strokes with minor or no disability), and 4 deaths (0.4%) occurred (2 deaths caused by myocardial infarction, 1 caused by intracranial hemorrhage, and 1 caused by stroke). Operative management of CR (n = 16) included patch angioplasty in 12 cases (autologous vein patches in 10 cases and synthetic patches in 2 cases), whereas interposition grafting was used in 4 cases (saphenous vein in 3 instances and synthetic [polytetrafluoroethylene] in one case). No strokes or deaths were observed. One recurrent laryngeal nerve palsy occurred (6.2%). Among the 16 patients undergoing 17 CAS procedures, the technical procedures were accomplished in all patients. No strokes or deaths occurred. No recurrent restenoses (50% or greater) have been identified within or adjacent to the CAS procedures. CONCLUSION: CR caused by myointimal hyperplasia can be managed by operative techniques or CAS with comparable periprocedural complications. Although long-term follow-up will be required to determine the incidence of recurrent restenosis, CAS may become the preferred procedure in these cases. A randomized clinical trial ultimately will be necessary to determine the role of CAS, as compared with that of operative management.

Retinoblastoma protein: a molecular regulator of chronic venous insufficiency.

PURPOSE: Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. METHODS: Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. RESULTS: Phosphorylated pRb from varicose GSVs exhibited intensities of 523 +/- 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 +/- 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. CONCLUSION: Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and the disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.

Patency of infrainguinal polytetrafluoroethylene bypass grafts with distal interposition vein cuffs.

Polytetrafluoroethylene (PTFE) prosthetic bypasses in the lower extremity have poor patency rates, particularly in limb salvage cases. Patency and limb salvage rates of PTFE bypasses supplemented by distal interposition vein cuffs were assessed in patients requiring revascularization for critical limb ischemia, in the absence of a suitable autologous saphenous vein. Between October 1993 and April 1996, 163 patients underwent 185 infrainguinal bypasses. Forty-three limbs in 42 patients (12 women, 30 men; mean age 67 years) did not have a suitable autologous saphenous vein (24%) and had femoropopliteal (20) and infrapopliteal (23) bypasses performed. Patients were examined prospectively at 3-month intervals during the first year and at 6-month intervals thereafter to determine graft patency and limb salvage. Postoperative anticoagulation with warfarin was used in 26 patients. Indications for operation included limb salvage in 41 extremities (21 rest pain/ulceration or gangrene, 20 rest pain alone), and disabling claudication in two. Patients were followed clinically for 2-30 months (mean 10 months). Cumulative 2-year life-table patencies for all grafts, femoropopliteal and infrapopliteal bypasses were 64%, 75% and 62%, respectively. Previous primary patencies at the authors' institution for PTFE bypasses without vein cuffs were 35%, 46% and 12% for the same categories. Cumulative life-table limb salvage for all PTFE/vein cuff bypasses in the present series was 76% compared with 37% in previous PTFE bypasses without vein cuffs. Adjunctive use of distal interposition vein cuffs improves prosthetic graft patency, while producing satisfactory limb salvage. Postoperative anticoagulation did not influence graft patency. PTFE/vein cuff for lower-extremity revascularization shows good 2-year patency and is an acceptable alternate conduit in patients with critical limb ischemia when autologous saphenous vein is absent.

A strategy for increasing use of autogenous hemodialysis access procedures: impact of preoperative noninvasive evaluation.

PURPOSE: We studied the efficacy of preoperative noninvasive assessment of the upper extremity to identify arteries and veins suitable for hemodialysis access to increase our use of autogenous fistulas (AF). METHODS: From Sep. 1, 1994, to Apr. 1, 1997, 172 patients who required chronic hemodialysis underwent segmental upper extremity Doppler pressures and duplex ultrasound with mapping of arteries and veins. The following criteria were necessary for satisfactory arterial inflow: absence of a pressure gradient between arms, patent palmar arch, and arterial lumen diameter 2.0 mm or more. The criteria necessary for satisfactory venous outflow were venous luminal diameter greater than or equal to 2.5 mm for AF and greater than or equal to 4.0 mm for synthetic bridging grafts (BG) and continuity with distal superficial veins in the arm. Intraoperative and duplex ultrasound measurements were compared. Contemporary experience was compared with the 2-year period (1992 to 1994) before implementation of the protocol. RESULTS: During the period from Sep. 1, 1994, to Apr. 1, 1997, 108 patients (63%) had AF, 52 (30%) had prosthetic BG, and 12 (7%) had permanent catheters (PC) placed. Early failure was seen in 8.3% of AFs. Primary cumulative patency rates were 83% for AF and 74% for BG at 1 year (p < 0.05), with a mean clinical follow-up of 15.2 months. No postoperative infections were observed with AF, whereas six infections (12%) were observed with BG and two (17%) with PC insertion. During the period from June 1, 1992, to Aug. 31, 1994, 183 procedures were performed with a distribution of 14% AF, 62% BG, and 24% PC. In this earlier period the AF early failure rate was 36%, and the patency rates were 48%, 63%, and 48% for AF, BG, and PC, respectively (mean follow-up, 13.8 months). CONCLUSION: A protocol of noninvasive assessment increased use of AFs. The cumulative patency rate of AFs was improved, and early failure rates were reduced when compared with the preceding institutional experience. Routine noninvasive assessment is recommended to document adequacy of arterial inflow and delineate venous outflow to maximize opportunities for AF.

Morphometric assessment of the dermal microcirculation in patients with chronic venous insufficiency.

PURPOSE: Ultrastructural assessments of the dermal microcirculation in patients with chronic venous insufficiency have been limited to qualitative morphologic descriptions of venous ulcer edges or venous stasis dermatitis. The purpose of this investigation was to quantify differences in endothelial cell structure and local cell type with emphasis on leukocytes and their relationship to arterioles, capillaries, and postcapillary venules (PCVs). METHODS: Two 4.0 mm punch biopsies were obtained from areas of dermal stasis skin changes in the gaiter region of the leg, as well as from noninvolved areas of skin in the ipsilateral thigh, from 35 patients: CEAP class 4 (11 patients), class 5 (9 patients), class 6 (10 patients), and five normal skin biopsies from patients without chronic venous insufficiency. Electron microscopy was performed on sections at 6700x and 23,800x magnification. At 6700x endothelial cell thickness was determined, and the number of fibroblasts, leukocytes, and mast cells were recorded relative to their proximity to arterioles, capillaries, and PCVs. Similarly, at 23,800x endothelial cell vesicle density, interendothelial junctional widths, and basal lamina thickness (cuff width) were measured. Preliminary evaluation for the presence of transforming growth factor-beta 1 (TGF-beta 1) was performed on three patients using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Quantitative measurements demonstrated increased mast cell content for class 4 and 5 patients around arterioles and PCVs and increased macrophage numbers for class 6 patients around PCVs (p < 0.05). Fibroblasts were the most common cells observed; however, no differences were demonstrated between groups. No differences were observed in interendothelial junctional widths or vesicle densities in arterioles, capillaries, or PCVs. Basal lamina thickness was increased only at the capillary level (p < 0.05). The results of RT-PCR for TGF-beta 1 messenger RNA were positive in the three patients studied. CONCLUSIONS: Our data suggest that (1) mast cells play a role in the pathogenesis of chronic venous insufficiency; (2) the effects of mast cells, macrophages, or both may be mediated in part by TGF-beta 1; and (3) capillary cuff formation is not associated with widened interendothelial gap junctions, but may be a result of enhanced vesicular transport rate or conformational changes in the interendothelial glycocalyx.

Outcome of complex venous reconstructions in patients with trauma.

PURPOSE: The role of complex venous reconstructions (CVRs) in patients with major trauma remains a controversial topic. This study evaluates the patency and clinical outcome of CVRs in a major urban trauma center. METHODS: Between 1979 and 1994 the records of 92 patients with 100 injuries to the iliac, femoral, and popliteal venous system were reviewed. The incidence of edema, pulmonary embolism, and limb loss was documented in 75 men and 17 women (mean age of 27 years, range 14 to 59 years). The 30-day patencies were assessed in all patients with either impedance plethysmography (n = 16), venography (n = 40), or duplex scan (n = 36). Long-term patencies were assessed in 14 patients monitored for 0.5 to 9 years (mean 3.2 years). RESULTS: Mechanisms of injury consisted of 58 gunshot wounds, 23 stab wounds, 6 shotgun wounds, and 5 blunt injuries. There were 112 associated injuries, 41 of which were concomitant arterial injuries. Forty-five of the 100 venous injuries were repaired with CVRs and included 6 (13%) spiral vein grafts, 8 (18%) panel vein grafts, 8 (18%) reversed saphenous vein interposition grafts, 8 (18%) end-to-end repairs, and 15 (33%) vein patch repairs. Thirty-day patency rates for these repairs were 50%, 50%, 75%, 88%, and 87%, respectively, and an overall patency rate of 73% was observed. The remaining 55 injuries were treated with ligation (n = 27) or lateral venorrhaphy (n = 28). The cumulative 30-day patency rate for all venous repairs was 81% (59 of 73). Fourteen patients, nine of whom had CVRs, were available for long-term follow-up. In this group CVRs demonstrated a 100% patency. One patient with a spiral vein graft repair of the common femoral vein had severe reflux causing intermittent edema and mild lipodermatosclerosis. No pulmonary emboli, limb loss, or deaths were identified in patients undergoing CVRs. CONCLUSION: Patients with CVRs had a 30-day patency rate of 73%. Of this group panel and spiral vein grafts were less successful, exhibiting only a 50% 30-day patency rate, whereas end-to-end and vein patch repairs were successful in 88% and 87% of cases, respectively. Our overall evaluation suggests that use of CVRs results in successful venous repair; however, the postoperative patency of interposition panel and spiral grafts suggests selective use of these techniques.