Salvage of Exposed Groin Vascular Grafts with Early Intervention Using Local Muscle Flaps.

BACKGROUND: Peripheral vascular surgery may be complicated by wound infection and potential graft exposure in the groin area. Muscle flap coverage of the graft has been promoted to address these wound complications. The authors present their findings regarding graft salvage rates and patient outcomes using local muscle flaps to address vascular graft complications of the groin. METHODS: Data were obtained by retrospective cohort study of patients who underwent a local muscle flap procedure by a single surgeon following vascular graft complication in the groin. RESULTS: Seventeen patients undergoing local muscle flap coverage of a vascular graft were reviewed. Six men and 9 women, 51-80 years old, were included in the study. Wound complications in the groin occurred anywhere from 3 days to 3.5 years following graft placement. Graft exposure was the most common presenting complication (14 of 17 patients). Muscle flap coverage occurred within 15 days of complication presentation in all patients (average, 6.4 days). Seven of the 15 patients experienced postoperative complications within 6 months of the procedure, most commonly wound dehiscence. However, analysis demonstrated that vascular grafts were successfully salvaged in 10 of the 17 patients (59%) over the course of follow-up (range, 104-1748 days). Average time to muscle flap coverage was 4.2 days in patients who retained the graft and 9.6 days in patients who ultimately lost their vascular graft. CONCLUSION: The authors demonstrate improved vascular graft salvage rate when local muscle flap procedure is performed early after initial wound complication presentation.

Anatomical and Surgical Concepts in Lymphatic Regeneration.

Chronic post-surgical lymphedema is common condition that afflicts nearly 2 million Americans. In the USA, it is most commonly encountered in the upper extremities of patients who have undergone axillary lymph node dissection for breast cancer. Lymphedema has a significant negative effect on cosmesis, limb function, and overall quality of life. Despite the impact of this condition, very little is known about how to effectively prevent or treat lymphedema. While therapeutic options for chronic extremity lymphedema remain limited, several surgical approaches have been suggested. These include techniques aimed at reducing limb volume, as well as techniques that aim to reconstitute disrupted lymphatic channels. Operations proposed to re-establish lymphatic continuity include lymphatico-venous anastomoses, lymphatico-lymphatico anastomoses, and tissue transfer.

Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-beta1-mediated tissue fibrosis.

Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-beta1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-beta1 on LECs in vitro. Radiation caused mild edema that resolved after 12-24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM-/- mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-beta1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-beta1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction.

Tissue expander breast reconstruction is not associated with an increased risk of lymphedema.

BACKGROUND: Recent reports have demonstrated that lymphedema can occur after even minor pertubation of the axillary region such as sentinel lymph node biopsy (SLNB). The impact of breast reconstruction on the development of lymphedema, however, remains unknown. Therefore, the purpose of this study was to determine the impact of immediate tissue expander breast reconstruction on the risk of developing lymphedema. MATERIALS AND METHODS: We identified patients who had undergone mastectomy with SLNB or SLNB and axillary lymph node dissection (ALND) with or without breast reconstruction using our prospectively maintained lymphedema and breast reconstruction databases. The development of lymphedema was evaluated prospectively using arm measurements and a validated questionnaire. Associations between variables were examined. Logistic regression was used to examine the association of reconstruction on prevalence of lymphedema while adjusting individually for BMI, age, and weight gain after surgery. RESULTS: Characteristics of patients with or without reconstruction were similar except for age, BMI, and weight gain since surgery. Median follow-up was 5 years. Among patients treated with mastectomy with SLNB or SLNB/ALND, those undergoing reconstruction had a lower rate of measured lymphedema than those who did not (5% vs. 18%, P < .0004). The reconstructed group also had fewer patients with both measured and self-reported lymphedema (3% vs. 12%, P < .002). Differences in the rates of measured lymphedema between groups persisted following univariate logistical regression for differences in age, BMI, and weight gain. CONCLUSIONS: Tissue expander breast reconstruction in patients undergoing SLNB or SLNB/ALND does not increase the risk of developing measured or perceived lymphedema.

Fibrosis is a key inhibitor of lymphatic regeneration.

BACKGROUND: Lymphedema is a common debilitating sequela of lymph node dissection. Although numerous clinical studies suggest that factors that lead to fibrosis are associated with the development of lymphedema, this relationship has not been proven. The purpose of these experiments was therefore to evaluate lymphatic regeneration in the setting of variable soft-tissue fibrosis. METHODS: A section of mouse tail skin including the capillary and collecting lymphatics was excised. Experimental animals (n = 20) were treated with topical collagen type I gel and a moist dressing, whereas control animals (n = 20) underwent excision followed by moist dressing alone. Fibrosis, acute lymphedema, lymphatic function, gene expression, lymphatic endothelial cell proliferation, and lymphatic fibrosis were evaluated at various time points. RESULTS: Collagen gel treatment significantly decreased fibrosis, with an attendant decrease in acute lymphedema and improved lymphatic function. Tails treated with collagen gel demonstrated greater numbers of lymphatic vessels, more normal lymphatic architecture, and more proliferating lymphatic endothelial cells. These findings appeared to be independent of vascular endothelial growth factor C expression. Decreased fibrosis was associated with a significant decrease in the expression of extracellular matrix components. Finally, decreased soft-tissue fibrosis was associated with a significant decrease in lymphatic fibrosis as evidenced by the number of lymphatic endothelial cells that coexpressed lymphatic and fibroblast markers. CONCLUSIONS: Soft-tissue fibrosis is associated with impairment in lymphatic regeneration and lymphatic function. These defects occur as a consequence of impaired lymphatic endothelial cell proliferation, abnormal lymphatic microarchitecture, and lymphatic fibrosis. Inhibition of fibrosis using a simple topical dressing can markedly accelerate lymphatic repair and promote regeneration of normal capillary lymphatics.

TGF-beta1 is a negative regulator of lymphatic regeneration during wound repair.

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -beta1 (TGF-beta1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-beta1 on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-beta1 expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-beta1 on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-beta1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-beta1 to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-beta1 inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-beta1 caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-beta1 during wound repair resulted in lymphatic fibrosis and the coexpression of alpha-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-beta1 expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-beta1 expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-beta1 expression may be useful in promoting more rapid lymphatic regeneration.