Makoto Samura

Significance of Ultrasound Examination of Skin and Subcutaneous Tissue in Secondary Lower Extremity Lymphedema

OBJECTIVES To clarify whether ultrasound findings of skin and subcutaneous tissue represent the severity of lymphedema. MATERIALS AND METHODS Thirty-five patients with secondary lower extremity lymphedema caused by intrapelvic lymph node dissection during cancer surgery, who first visited our clinic between April 2009 and March 2012, were studied retrospectively. At their first visit, skin thickness, subcutaneous tissue thickness, and subcutaneous echogenicity were assessed at 8 points on the thigh and leg of both legs using an 11-MHz ultrasound transducer. These findings correlated with the International Society of Lymphology (ISL) clinical stage. RESULTS Skin thickness, subcutaneous tissue thickness, and subcutaneous echogenicity all showed significant positive correlation with the ISL stage. However, measuring skin and subcutaneous tissue thicknesses was not feasible in 29%-71% of scanning points in stage III legs because of poor delineation of boundaries at the dermo-hypodermal junction and the upper boundary of the muscular fascia. However, subcutaneous echogenicity was assessable at all scanning points and was linearly correlated with ISL stage. CONCLUSION Evaluating subcutaneous echogenicity is feasible even with low-resolution ultrasound and reflects the ISL stage. These findings may thus be valuable to objectively represent the severity of extremity lymphedema.

Subcutaneous Tissue Ultrasonography in Legs with Dependent Edema and Secondary Lymphedema

OBJECTIVES To elucidate the differences in subcutaneous ultrasound findings between dependent edema (DE) and secondary lower extremity lymphedema (LE). MATERIALS AND METHODS Twenty legs in 10 patients with DE and 54 legs in 35 patients with LE, who first visited our clinic between April 2009 and December 2012, were studied retrospectively. Subcutaneous echogenicity and echo-free space (EFS) were assessed at 8 points on the thigh and leg using an 8-12 MHz ultrasound transducer. RESULTS In DE, echogenicity was increased most in the lower leg, without a difference between the medial and lateral side. The EFS was most remarkable in the lower leg, and the lateral side was more severe. In the early stages of LE, echogenicity was similarly increased in the medial thigh and in the leg, while remarkable EFS was observed only in the lower leg. As clinical severity progressed, echogenicity increased in all parts of the lower extremity. EFS also increased in all parts of the leg, but the lower leg was still the most severe. CONCLUSION Echogenicity seemed to progress differently in DE and LE, but EFS progressed similarly and according to gravity. The current ultrasound findings may have added some diagnostic value in differentiating these conditions.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography for Diagnosis of Infected Aortic Aneurysms

BACKGROUND Infected aortic aneurysms are diagnosed on the basis of a positive bacterial blood culture, clinical evidence of inflammation, and morphologic findings on computed tomography (CT). However, preoperative diagnosis is often difficult because blood cultures are frequently negative and patients can be asymptomatic. Because therapeutic approaches differ significantly, it is vital to determine whether an aortic aneurysm is infected prior to surgery. METHODS From June 2007 to July 2012, we investigated 11 cases of suspected infected aortic aneurysm using fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET/CT). In addition to contrast-enhanced CT examination, blood culture and histologic examinations were performed to aid diagnosis. RESULTS Patients with a final diagnosis of infected aortic aneurysms showed a maximum standard uptake value (SUVmax) of >4.46, whereas infection-free cases had an SUVmax of <2.59 (mean 6.5 ± 1.8 vs. 1.9 ± 0.5; P < 0.001). CONCLUSION FDG-PET/CT examination is useful in the diagnosis of infected aortic aneurysms.

Influence of aging on the quantity and quality of human cardiac stem cells.

Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated b-galactosidase and the DNA damage marker, gH2AX, showed a slightly higher trend in CDCs from older patients (≥65 years). The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-b varied among samples, and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients.

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.

Hypoxic preconditioning reinforces cellular functions of autologous peripheral blood-derived cells in rabbit hindlimb ischemia model.

Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches with transplanted PBMNCs show poor therapeutic effects in severe ischemia patients. In this study, we used autograft models to determine whether hypoxic pretreatment effectively enhances the cellular functions of PBMNCs and improves hindlimb ischemia. Rabbit PBMNCs were cultured in the hypoxic condition. After pretreatment, cell adhesion, stress resistance, and expression of angiogenic factor were evaluated in vitro. To examine in vivo effects, we autografted preconditioned PBMNCs into a rabbit hindlimb ischemia model on postoperative day (POD) 7. Preconditioned PBMNCs displayed significantly enhanced functional capacities in resistance to oxidative stress, cell viability, and production of vascular endothelial growth factor. In addition, autologous transplantation of preconditioned PBMNCs significantly induced new vessels and improved limb blood flow. Importantly, preconditioned PBMNCs can accelerate vessel formation despite transplantation on POD 7, whereas untreated PBMNCs showed poor vascularization. Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible approach for increasing the retention of transplanted cells and enhancing therapeutic angiogenesis in ischemic tissue.

Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p

Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24 h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24 h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3′ UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia.

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.

Skin and Subcutaneous Tissue Strain in Legs with Lymphedema and Lipodermatosclerosis

We compared skin and subcutaneous tissue strains in legs with lymphedema (LE) of varying severity and legs with lipodermatosclerosis (LDS) using real-time tissue elastography. Strain was assessed at the inner thigh and calf in 62 legs with LE (International Society of Lymphology [ISL] stage 0: 16, stage I: 5, stage II: 28, late stage II: 7, stage III: 6) and 15 legs with LDS. In thighs and calves with LE, skin strain and subcutaneous tissue strain did not significantly differ between ISL stage 0, that is, asymptomatic legs, and other stages. However, strain values in calves with LDS were lower than values in calves with stage 0, II and late II LE. These results indicate that skin and subcutaneous tissue strains were not lower in legs with symptomatic LE than in asymptomatic legs until an advanced stage.

Chimney Technique for Aortic Dissection Involving an Aberrant Right Subclavian Artery

We report a case involving a ruptured acute type B aortic dissection originating from an aberrant right subclavian artery (ARSA). A thoracic stent-graft was deployed in the distal arch close to the origin of the ARSA; the entry site at the origin of the ARSA was embolized with metallic coils. Perfusion of the left subclavian artery was preserved without a surgical bypass by using a chimney graft. This procedure is a feasible and less invasive treatment for high-risk sternotomy patients and is an effective strategy for acute aortic dissections involving an ARSA.