Five-year follow-up of randomized clinical trial for pre-emptive inferior mesenteric artery embolization during endovascular aneurysm repair.

INTRODUCTION: Type II endoleak (T2EL) is the most common type of endoleak after endovascular aneurysm repair (EVAR) and a common indication for reintervention due to late sac enlargement. Although pre-emptive embolization of the inferior mesenteric artery (IMA) has been proposed to prevent this, no studies have prospectively demonstrated its efficacy. This study aimed to prove the validity of IMA embolization during EVAR in selective cases by analyzing the mid-term outcomes of a randomized clinical trial (RCT). METHODS: This single-center, parallel-group, non-blinded RCT included participants at high risk of T2EL, characterized by a patent IMA in conjunction with one or more following risk factors: a patent IMA ≥3 mm in diameter, lumbar arteries ≥2 mm in diameter, or an aortoiliac-type aneurysm. The participants were randomly assigned to two groups in a 1:1 ratio: one undergoing EVAR with IMA embolization and the other without. The primary endpoint was T2EL occurrence. The secondary endpoints included aneurysm sac changes and reintervention. In addition to RCT participants, outcomes of patients with low-risk of T2EL were also analyzed. RESULTS: The embolization and non-embolization groups each contained 53 patients. Five-year follow-up after the last patient enrolment revealed that T2ELs occurred in 28.3% and 54.7% of patients in the IMA embolization and non-embolization groups, respectively (P=.006). Both freedom from T2EL-related sac enlargement ≥5 mm and cumulative incidence of sac shrinkage ≥5 mm were significantly higher in the IMA embolization group than in the non-embolization group (95.5% vs. 73.6% at 5 years; P=.021, 54.2% vs. 33.6% at 5 years; P=.039). The freedom from T2EL-related sac enlargement ≥10 mm, an alternative indicator for T2EL-related reintervention, showed similar results (100% vs. 90.4% at 5 years; P=.019). Outcomes in the low-risk group were preferable than those in the non-embolization group and comparable to those in the IMA embolization group. CONCLUSION: A lower threshold for pre-emptive IMA embolization when implementing EVAR would be more appropriate if limited to patients at high risk of T2ELs.

Dependent Leg Edema in Older Patients with or without Skin Lesion.

Objective: This study aimed to clarify the features and causes of dependent edema (DE) in the legs of patients in geriatrics. Patients and Methods: We retrospectively reviewed 224 patients with DE, aged ≥65 years, who visited our clinic from April 2009-March 2022. DE was defined as bilateral leg edema in patients without known systemic edemagenic conditions, venous insufficiency confirmed by duplex venous scanning, or a cancer treatment history in the pelvic/inguinal lesions. Results: The median patient age was 77 years (range: 65-94 years), where 74% were female. Overall, 198 patients (88%) had gait disturbances caused mainly by musculoskeletal disorders, but 58 (26%) walked without aid. Compared with patients with DE only (N=129), patients with DE and venous stasis-related skin lesions (N=95) included a larger number of those with obesity than did those with DE only (26% vs. 14%, p=0.02). Conclusion: The primary cause of DE in older patients was the sedentary lifestyle secondary to aging and gait disturbance, not solely because of reduced leg function. The complications of obesity are associated with increased venous stasis-related skin lesions.

Leg volume reduction during tiptoe movement is caused by venous ejection and calf muscle contraction.

OBJECTIVES: To clarify the cause of leg volume reduction during tiptoe movement in the standing position. METHODS: The right legs of 20 participants were assessed. The participants performed tiptoe movement in the supine position, and then stood up and performed the tiptoe movement and ankle dorsiflexion. Leg volume changes were recorded continuously using air plethysmography. RESULTS: Differences between leg volume changes due to tiptoe movement and the refilling volumes were not significantly different between the supine (59 mL) and standing (49 mL) positions, indicating that this amount of motion artifact was included in the downward trace recorded by tiptoe movement in the standing position. CONCLUSIONS: Leg volume reduction during tiptoe movement in the standing position included a significant amount of motion artifacts. Therefore, it may be difficult to accurately measure the ejection volume using tiptoe movement in the standing position.

Effects of leg compression and calf muscle contraction by active ankle motion on venous hemodynamics in sitting individuals.

OBJECTIVES: To clarify the effects of compression and active ankle motion on venous hemodynamics in healthy sitting individuals. METHODS: In the sitting position, 14 participants performed plantar flexion and dorsiflexion of the ankle for 3 s each without compression. Changes in the calf volume were recorded using air plethysmography. Subsequently, the process was repeated with the application of tubular elastic bandage (TEB), followed by anti-thrombotic stocking (ATS). RESULTS: The median interface pressure at the calf was 16 mmHg with TEB and 21 mmHg with ATS. Without compression (N), the median venous volume was 76 mL. This was reduced to 58 mL with TEB and 56 mL with ATS (p < .01 vs. N for both). On the other hand, ejection volume by plantar flexion in N (27 mL) was not significantly changed with TEB (31 mL) or ATS (31 mL). Also, ejection volume by dorsiflexion in N (53 mL, p < .001 vs. plantar flexion) was not significantly changed with TEB (53 mL, p < .01 vs. plantar flexion) or ATS (41 mL, p < .05 vs. plantar flexion). CONCLUSIONS: The venous volume, which is defined as the change in enclosed calf volume from elevation to dependency, in the sitting position reduced similarly with TEB and ATS; however, the ejection volumes did not change significantly. Dorsiflexion exerted a larger ejection volume than plantar flexion in the sitting position.

Treatment Results of Endovascular Aneurysm Repair Using the Parallel Stent-Graft Double D Technique for Distal Saccular Abdominal Aortic Aneurysms and Common Iliac Aneurysms.

BACKGROUND: Endovascular aneurysm repair (EVAR) using a bifurcated stent graft may involve technical challenges when aortic disease (aneurysm or dissection) consists of a length <70 mm between the inferior renal artery and aortic bifurcation or narrow aortic bifurcation that is common in asymmetric distal abdominal aortic aneurysms (AAAs) or iliac artery aneurysms (IAAs). We use EVAR with the double D technique (DDT-EVAR) for such cases, which involves straight type of stent grafts with same diameter in left and right that are deployed parallel to an aortic cuff that has been previously placed. In addition, DDT-EVAR can preserve the inferior mesenteric artery (IMA) for IAA. METHODS: DDT-EVAR was performed for 21 of 910 (2%) cases from April 2007 to April 2019 at our institution. The median patient age was 74 years (range, 52-85). Nineteen patients (90%) were men. Six patients (all saccular; 1 rupture) had AAAs, 12 had IAAs, and 3 had chronic type B aortic dissociation (TBAD) for re-entry closure. AAA and IAA had diameters of 45 mm (range, 34-71) and 34 mm (range, 25-58), respectively. An aortic cuff was used for 19 (90%) cases. Endurant II (Medtronic, Santa Rosa, CA) was used for 12 cases. The Excluder (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used for 7 cases. Endurant II was used for 20 cases, and the VBX (W.L. Gore & Associates, Inc) was used for 1 case as stent-graft limbs. RESULTS: The procedural success rate was 100%. The median operative time was 146 min (range, 88-324). IMA planned for preservation was successful for all 12 cases. Type I and type III endoleaks were not observed. With TBAD, flow to the false lumen decreased or disappeared, and no complications during the hospital stay were associated with the procedure. For 2 patients whose procedure involved Endurant II stent-graft limb, limb occlusions were observed postoperatively, and reintervention was required. No other patients required additional treatment at a median follow-up of 18 months (range, 4-50). CONCLUSIONS: DDT-EVAR is a safe and straightforward technique for the treatment of distal AAA, common iliac artery aneurysm, and TBAD. It may help preserve the IMA and internal iliac artery, even when it is impossible to preserve them with a bifurcated stent graft.

Extracellular Fluid Content in the Legs of Patients with Chronic Venous Disease.

BACKGROUND: This study aimed to determine the factors that affect the extracellular fluid (ECF) content in the legs of patients with chronic venous disease (CVD). METHODS: Bioimpedance analysis and air plethysmography (APG) were performed in 79 patients with CVD who visited our clinic between September 2016 and March 2019. The normal right legs (N) of 14 healthy volunteers were also reviewed for comparison. The ratio of ECF resistance (Re) of the leg to that of the arm (ReL/ReA) was used to express the ECF content in the tested leg. The severity of CVD was expressed using the clinical, etiological, anatomical, and pathophysiological (CEAP) classification. RESULTS: The ReL/ReA decreased as the CEAP class increased (N: median; 0.81 [range 0.66-0.95], C0-1: 0.79 [0.60-0.98], C2: 0.77 [0.56-1.08], C3: 0.67 [0.57-0.85], C4: 0.64 [0.44-0.89]). Older age, female sex, and CEAP class affected the ReL/ReA, but body mass index did not. The ReL/ReA did not correlate with the parameters that were derived from APG, including the venous filling index. CONCLUSIONS: We found that the ECF content in legs of patients with CVD might be primarily affected by patient-related factors and CEAP class, as opposed to venous hemodynamics.

Endovascular Aneurysm Repair With Inferior Mesenteric Artery Embolization for Preventing Type II Endoleak: A Prospective Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of inferior mesenteric artery (IMA) embolization during endovascular aneurysm repair (EVAR) in patients at high risk of type II endoleak (T2EL) in randomized controlled trial (RCT). SUMMARY BACKGROUND DATA: Several studies have demonstrated a reduction of T2EL by IMA embolization before EVAR. However, there have been no RCT confirming the efficacy of IMA embolization. METHODS: Patients scheduled for elective EVAR between April 2014 and March 2018 were eligible. Patients at high risk of T2EL (IMA patency with IMA ≥3 mm, LAs ≥2 mm, or an aortoiliac-type aneurysm) were prospectively randomized to receive EVAR with or without IMA embolization. The primary endpoint was occurrence of T2EL during follow-up. Secondary endpoints included aneurysmal sac changes, adverse events from IMA embolization, and reintervention rate due to T2EL. This trial is registered with the University Hospital Medical Information Network, number UMIN000022147. RESULTS: One hundred thirteen patients had high risk and 106 were randomized. In the intention-to-treat analysis, the incidence of T2EL was significantly lower in the embolization group [24.5% vs 49.1%; P = 0.009, absolute risk reduction = 24.5%; 95% confidence interval (CI), 6.2-40.5, number needed to treat = 4.1; 95% CI, 2.5-16.1]. The aneurysmal sac shrunk significantly more in the embolization group (-5.7 ±â€Š7.3 mm vs -2.8 ±â€Š6.6 mm; P = 0.037), and the incidence of aneurysmal sac growth related to T2EL was significantly lower in the embolization group (3.8% vs 17.0%; P = 0.030). There were no complications related to IMA embolization or reinterventions associated with T2EL. CONCLUSIONS: Our results demonstrated the effectiveness of IMA embolization during EVAR in high-risk patients for the prevention of T2EL, which is suggested for avoiding aneurysmal sac enlargement related to T2EL.

Regular Compression Therapy May Not Be Necessary for Lymphedema in Arms without a Subcutaneous Echo-Free Space.

BACKGROUND: To study the effect of prolonged complex decongestive therapy (CDT) on lymphedema in arms without a subcutaneous echo-free space (SEFS) on subcutaneous tissue ultrasonography. METHODS: Fifty-one patients with arm lymphedema treated for longer than 1 year using CDT in our clinic were retrospectively evaluated. Before starting CDT, subcutaneous tissue ultrasonography was performed to examine for the presence of an SEFS. Two-stage CDT was performed as recommended by the International Society of Lymphology. Limb circumference was measured, and limb volume was calculated at the initial and latest visits. RESULTS: In patients with lymphedema in which SEFS was observed anywhere in the arm on the initial visit (n = 25), the edema ratio was significantly reduced by a median of -15% (range, -106% to 17%; P < 0.001). On the other hand, in the arms with lymphedema in which SEFS was not observed (SEFS[-], n = 26), the edema ratio was not changed significantly by CDT (median, 1% [range, -30% to 23%]). In arms without an SEFS that were not treated using arm sleeves regularly (n = 15), no increase in edema ratio was observed (median, 1% [range, -29% to 16%]). CONCLUSIONS: In arms with lymphedema without SEFS, the effect of CDT on the reduction of arm volume is limited.

Perioperative variations in indices derived from noninvasive assessments to detect postmastectomy lymphedema.

OBJECTIVE: This study aimed to clarify the variations in indices derived from noninvasive assessments for the early detection of postmastectomy lymphedema (LE) from 1 month preoperatively until 2 years postoperatively. METHODS: In total, 120 patients who underwent surgery for breast cancer in our institution were prospectively followed up with a questionnaire for arm swelling as well as with tape measurements, bioimpedance analysis (BIA), and skin and subcutaneous tissue ultrasound at 1 month before and 3, 6, 12, 18, and 24 months after surgery. RESULTS: Ninety-seven patients completed the study. Among 93 patients who did not present with LE, 9% complained of arm swelling even before surgery, and the incidence peaked at 17% at 6 months after surgery. There were no differences in the circumferences of the upper arm, forearm, and hand between sides throughout the study period. However, the postoperative circumference values of the upper arm only on the operation side were slightly increased compared with the preoperative values. The mean excess fluid in the arm on the operation side compared with the contralateral side, as assessed by BIA, was nearly zero throughout the study period. There were no differences in subcutaneous echogenicity or skin and subcutaneous thicknesses between the sides throughout the study period. However, time-dependent increases in subcutaneous thicknesses were noticed on both sides. Four patients (4.1%) developed LE. In three of these patients, abnormality in the BIA was recorded 6 to 12 months before presentation. Immediately after presentation, the common findings included BIA abnormality and increased subcutaneous echogenicity and skin thickness in the medial forearm. CONCLUSIONS: In this study, a complaint of arm swelling was not sensitive enough for detection of the early onset of LE because a certain number of patients constantly complained of this symptom. Measurements of circumference might help in the diagnosis of LE onset, but this method is not specific enough because these measurements are also affected by various factors. However, BIA and skin and subcutaneous ultrasound were identified as potential tools for the early detection of LE.

Using bifurcated endoprosthesis after iliac artery recanalization for concomitant abdominal aortic aneurysm and chronic total occlusions of access routes.

OBJECTIVE: Concurrent abdominal aortic aneurysm (AAA) and unilateral iliac occlusion is a challenge in the implantation of bifurcated stent grafts (BFGs). The endovascular approach is less invasive than open surgery; the aortouni-iliac (AUI) graft with crossover femorofemoral bypass (CFFB) has many problems associated with extra-anatomic reconstruction. We attempted endovascular aneurysm repair (EVAR) using BFGs in such cases and evaluated the outcomes. METHODS: This was a retrospective study. Between October 2012 and December 2017, there were 649 patients who underwent surgery for AAA, of whom 32 patients underwent open reconstruction and 617 patients underwent endovascular aneurysm repair; 15 patients with unilateral occluded iliac arteries and AAA were included. The analysis included patients with unilateral iliac chronic total occlusion (CTO). The intraoperative, postoperative, and follow-up variables were reviewed. RESULTS: The occluded lesions were the common iliac artery in 5 patients, the common iliac artery-external iliac artery (EIA) in 2 patients, the EIA in 7 patients, and the EIA-common femoral artery in 1 patient. The mean occlusive length was 89.7 ± 43.6 mm, and the mean AAA size was 54.6 ± 5.6 mm. Technical success was achieved in 13 patients (87%). All patients underwent recanalization through the true lumen and stent placement. The only procedure-related complication was distal embolism, which was treated with intraoperative thrombectomy. Recanalization of CTO lesions was not possible in two patients (13%), who underwent AUI graft placement with CFFB. The 30-day mortality and morbidity rates were 0%. The mean follow-up periods were 12 and 32 months for patients who underwent BFG placement and AUI graft placement with CFFB, respectively. During follow-up, the primary patency rate of successfully recanalized arteries was 100%. Aneurysm size decreased in four patients who underwent BFG placement; no change was seen in the other 11 patients. Freedom from aneurysm-related events was 100%; no patient needed secondary interventions. All patients with claudication pain preoperatively reported improvement in their symptoms during follow-up. In addition, the ankle-brachial index improved significantly from 0.51 ± 0.25 preoperatively to 0.88 ± 0.20 postoperatively (P < .001) in patients who underwent BFG placement. CONCLUSIONS: Recanalization of unilateral iliac CTO lesions and placement of BFG in cases with concomitant aneurysmal disease and unilateral iliac occlusive disease demonstrated a significant primary patency rate with improvements in claudication and ankle-brachial index.

Aggressive Decongestion in Limbs with Lymphedema without Subcutaneous Echo-Free Space.

BACKGROUND: To study the impact of aggressive decongestion in limbs with lymphedema without subcutaneous echo-free space (SEFS) in subcutaneous tissue ultrasonography. METHODS: In 13 patients with arm lymphedema (ALE) (13 arms) and 16 patients with leg lymphedema (LLE) (18 legs) without SEFS, an aggressive decongestion was performed as the first phase of complex decongestive therapy. Measurements of circumference and calculation of limb volume were performed before and after the treatment. RESULTS: In ALE, no significant reduction in arm volume (median -63 [range -251 to 176] mL) or edema ratio (-4 [-15 to 12]%) was confirmed. On the other hand, a small but significant reduction in leg volume (-207 [-834 to 131] mL, P < 0.001) and edema ratio (-4 [-14 to 2]%, P < 0.01) was confirmed in LLE. CONCLUSION: In limbs with lymphedema without SEFS, the impact of aggressive decongestion seemed limited.

Midterm Outcomes of Endovascular Aortic Aneurysm Repair with Carbon Dioxide-Guided Angiography.

BACKGROUND: Although iodinated contrast (IC) agents are commonly used in endovascular aneurysm repair (EVAR), perioperative use in patients with renal dysfunction or IC allergies is avoided. Carbon dioxide (CO2)-guided angiography is a promising alternative. We aimed to evaluate short-term and midterm outcomes of EVAR using CO2-guided angiography. METHODS: Three hundred eighty-one patients who underwent EVAR from January 2012 to September 2016 were retrospectively reviewed and divided into an IC-EVAR group (n = 351) and CO2-EVAR group (n = 30). Subjects in the CO2-EVAR group had severe renal dysfunction (n = 27) and IC allergy (n = 4). Intraoperative, postoperative, and follow-up variables were compared. RESULTS: Compared with the IC-EVAR group, preoperative serum creatinine level was significantly higher (2.0 vs. 0.92 mg/dL, P < 0.0001) and mean IC dose was significantly lower (18 vs. 55 mL, P < 0.0001) in the CO2-EVAR group. The fluoroscopy time, operative time, number of stent grafts placed, and technical success rates of the groups were similar; no type I and/or type III endoleaks were detected on completion angiography. There was no acute kidney injury and one case of intestinal necrosis in the CO2-EVAR group, potentially due to cholesterol embolism. Postoperative endoleak, enlargement of aneurysms, survival, freedom from secondary intervention, and renal function change up to 3 months, postoperatively, were similar between the groups. CONCLUSIONS: CO2-EVAR is technically feasible and exhibits prominent renal protection. However, consideration of the aortic lumen status remains an important challenge.

Identification of Anatomical Risk Factors for Type II Endoleak to Guide Selective Inferior Mesenteric Artery Embolization.

BACKGROUND: It is unclear which patients are the best candidates for inferior mesenteric artery (IMA) embolization to reduce type II endoleak (ELII). Therefore, this study aimed to identify the anatomical risk factors for ELII after endovascular aneurysm repair (EVAR) and to determine the best candidates for preventative, preoperative IMA embolization. MATERIALS AND METHODS: Between April 2007 and September 2014, 196 patients underwent standard EVAR. Anatomical risk factors of postoperative, persistent ELII were detected using logistic regression analysis. Preoperative treatment of the IMA occlusion in patients with anatomical risk factors was performed to reduce ELII. RESULTS: ELII was detected in 48 patients (24.5%). Overall, patency of the IMA (odds ratio [OR], 4.13; P = 0.004) and lumbar artery (LA) diameter ≥2.0 mm (OR, 3.30; P = 0.008) were significant risk factors for ELII, whereas an Endurant stent graft protected against ELII (OR, 0.22; P = 0.023). However, in patients with patent IMA, IMA diameter ≥3.0 mm (OR, 4.09; P = 0.011), LA diameter ≥2.0 mm (OR, 3.16; P = 0.043), and aortoiliac aneurysm (OR, 6.36; P = 0.026) were significant risk factors for ELII. Incidence rates of ELII in patients with and without these factors were 37.8% and 11.2%, respectively. ELII did not occur in patients with risk factors who underwent treatment of preoperative IMA occlusion. CONCLUSIONS: Patients with these risk factors are the candidates for undergoing treatment of preoperative IMA occlusion to reduce ELII.

Innovative Procedure for Inferior Mesenteric Artery Embolization Using the Amplatzer Vascular Plug 4 during Endovascular Aneurysm Repair.

PURPOSE: The aim of this study is to present an easy and quick technique for embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR). TECHNIQUE: We performed IMA embolization using a conventional EVAR device alone with the femoral artery approach during EVAR, which has not been reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the femoral artery into the site around the IMA. Second, cannulation is performed in the IMA with an angiography catheter having a 0.038-inch inner lumen that is used for gate cannulation during EVAR. Third, IMA embolization is performed using the Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates cannulation of the IMA, and its combination with a stent-graft balloon allows the AVP4 to be placed at the root of the IMA without deviation of the catheter. The success rate of the procedure was 90.9% (30/33 cases). The median procedure time was 11.6 min. No complications due to IMA embolization were noted. CONCLUSION: This procedure enables safe and quick placement of the AVP4 in the IMA using the catheter insertion approach from the femoral artery, which has been conventionally regarded as difficult.

Treatment Options for Celiac Stenosis and Pancreaticoduodenal Artery Aneurysms.

Celiac stenosis may result in a pancreaticoduodenal artery aneurysm (PDAA). Celiac stenosis with a PDAA is rare and treatment guidelines are absent. Here, we report 4 cases of celiac stenosis treated using different methods. Of these, 3 involved PDAAs. The PDAAs were successfully treated with coil embolization. For celiac stenosis, we performed open surgery for decompression in 1 patient, stenting in 2 patients, and bypass grafting in 1 patient. In the patients who underwent stenting, stent-associated thrombosis occurred. PDAAs can be treated with coil embolization; however, treatment of celiac stenosis with the endovascular approach might be difficult.

Differentiation of functional venous insufficiency and leg lymphedema complicated by functional venous insufficiency using subcutaneous tissue ultrasonography.

OBJECTIVE: To use subcutaneous ultrasonography to differentiate legs with edema because of obesity-related functional venous insufficiency (FVIob), immobility-related FVI (FVIim), secondary lymphedema (LE), LE complicated by obesity (LEob), and LE complicated by immobility (LEim). METHODS: Ninety-nine legs with edema (16 FVIob, 32 FVIim, 22 LE, 9 LEob, and 20 LEim), and 10 normal legs were examined. Subcutaneous tissue ultrasonography was performed at eight points (medial, lateral, upper, lower, thigh, and calf) in each leg. Subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) were assessed, and each graded as 0, 1, and 2 according to their severity. RESULTS: In normal legs, SEG and SEFS were graded 0 in almost all parts of the leg. SEG was diffusely increased in FVIob, whereas SEG was increased in accordance with gravity in FVIim (upper medial thigh, 0.6 ± 0.5 vs lower medial calf, 1.2 ± 0.4; P < .001). In LE, SEG was increased in the medial side, particularly evident in upper thigh (upper medial thigh, 1.1 ± 0.4 vs upper lateral thigh, 0.6 ± 0.6; P < .01). SEFS was increased in accordance with gravity in all of these legs (FVIob: upper medial thigh, 0.2 ± 0.4 vs lower medial calf, 0.7 ± 0.8; P = .05; FVIim: upper medial thigh, 0.1 ± 0.2 vs lower medial calf, 1.3 ± 0.7; P < .0001; LE: upper medial thigh, 0.4 ± 0.7 vs lower medial calf, 0.9 ± 0.9; P < .05). The increases of SEG and SEFS in legs with LEob or LEim were diffuse and similar. As determined via stepwise logistic regression analyses, the increases in SEG in the upper medial thigh and SEFS in the lower medial thigh in LE cases, the increases in SEG in the upper lateral thigh and SEFS in the lower lateral thigh in cases with obesity-related leg edema (ie, FVIob and LEob), and the increase in SEFS in the lower lateral calf in cases with immobility-related leg edema (ie, FVIim and LEim) were determined to be significant factors to characterize each leg edema. CONCLUSIONS: Differences in the extent and distribution of SEG and SEFS might help in differentiating LE from FVIob and FVIim, although assessment of LE complicated by obesity vs immobility remains difficult.

Skin and Subcutaneous Tissue Ultrasonography Features in Breast Cancer-Related Lymphedema.

Objective: To investigate skin, subepidermal low echogenic band (SELEB), and subcutaneous tissue (SCT) thickness as well as the degree of increase in subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) in arms with lymphedema (LE). Materials and Methods: The skin and SCT of both arms of 30 patients with unilateral stage II breast cancer-related LE were scanned at five points (medial/lateral upper arm/forearm and dorsum of the hand). SEG and SEFS grades were determined according to severity (range: 0-2). Results: All measured parameters, except the SEFS in the medial upper arm, were significantly higher on the LE side than on the normal (N) side. The parameters differed most remarkably in the medial forearm (MFA; skin: LE 1.7 ± 0.8 mm vs. N 0.8 ± 0.2 mm; SELEB: LE 1.0 ± 0.6 mm vs. N 0.3 ± 0.1 mm; SCT: LE 8.7 ± 3.4 mm vs. N 3.8 ± 2.0 mm; SEG: LE 0.9 ± 0.5 vs. N 0.1 ± 0.3; and SEFS: LE 0.5 ± 0.7 vs. N 0). Conclusion: The differences in the thickness of the skin, SELEB, and SCT and the SEG and SEFS grades between the LE and N arms seemed most evident in the MFA.

Combinatorial Treatment with Apelin-13 Enhances the Therapeutic Efficacy of a Preconditioned Cell-Based Therapy for Peripheral Ischemia.

Hypoxic pretreatment of peripheral blood mononuclear cells (PBMNCs) enhances therapeutic angiogenesis in ischemic tissues after cell transplantation. However, newly formed vessels generated using this approach are immature and insufficient for promoting functional recovery from severe ischemia. In this study, we examined whether apelin-13, a regulator of vessel maturation, could be an effective promoter of therapeutic angiogenesis, following severe limb ischemia. Combinatorial treatment of hypoxic preconditioned PBMNCs with apelin-13 resulted in increased blood perfusion and vascular reactivity in ischemic mouse hindlimbs compared with a monotherapy comprising each factor. Apelin-13 upregulated expression of PDGF-BB and TGF-ß1 in hypoxic PBMNCs, as well as that of PDGFR-ß in vascular smooth muscle cells (VSMCs). Proliferation and migration of VSMCs treated with apelin-13 was accelerated in the presence of PDGF-BB. Interestingly, expression of an apelin receptor, APJ, in PBMNC was increased under hypoxia but not under normoxia. In addition, an in vitro angiogenesis assay using a co-culture model comprising mouse thoracic aorta, hypoxic PBMNCs, and apelin-13 demonstrated that combinatorial treatment recruited mural cells to sprouted vessel outgrowths from the aortic ring, thereby promoting neovessel maturation. Thus, combinatorial injection of hypoxic PBMNCs and apelin-13 could be an effective therapeutic strategy for patients with severe ischemic diseases.

A study of increase in leg volume during complex physical therapy for leg lymphedema using subcutaneous tissue ultrasonography.

OBJECTIVE: The purpose of this study was to discuss the mode of increase in leg volume during complex physical therapy (CPT) for lymphedema using subcutaneous tissue ultrasonography. METHODS: Thirty-eight patients (51 legs) with secondary lymphedema who were treated by CPT for longer than 2 years (3.0 ± 0.8 years) at our clinic were studied. The leg circumferences were measured at every visit. Subcutaneous tissue ultrasonography was performed at the initial and latest visits. RESULTS: The overall change in leg volume was -284 ± 915 (range, -4588 to 1139) mL. Among them, the increase in leg volume was found in 18 legs; of those, 9 (1 in stage I, 7 in stage II, 1 in stage III) were adherent to hosiery use. In the legs whose average volume was decreased (group A, n = 33; mean, -821 [-4588 to -19] mL), the circumference had decreased in all the leg levels. However, in the legs whose average volumes had increased (group B, n = 18; mean, +449 [18-1139] mL), the circumference had increased in the thigh but remained unchanged or even decreased in the lower leg. In group B, subcutaneous thickness (SCT), subcutaneous echogenicity (SEG), and subcutaneous echo-free space (SEFS), assessed by ultrasonography, were found to have increased particularly in the lower medial thigh compared with those in group A (SCT change: group A, -1.5 ± 5.9 cm vs group B, 3.7 ± 5.4 cm [P < .05]; SEG grade change: group A, -0.3 ± 0.7 vs group B, 0.3 ± 0.7 [P < .05]; SEFS grade change: group A, -0.1 ± 0.7 vs group B, 0.4 ± 0.6 [P < .05]), whereas these remained unchanged or even decreased in the lower leg. CONCLUSIONS: Increase in leg volume during CPT might not be caused simply by noncompliance to hosiery use and seemed closely related to the increase in thigh circumferences, particularly the lower thigh, in which SCT, SEG, and SEFS were increased.