Efficacy and Safety of the 532-nm KTP and Long-Pulsed 1064-nm Neodymium-doped Yttrium Aluminum Garnet Laser for Treatment of Vascular Malformations.

BACKGROUND: Pulsed dye lasers (PDLs) are well-established for treatment of capillary malformations but are unable to penetrate the depth needed to treat deeper vascular lesions. A combined approach using a deeper penetrating wavelength with a "superficial" wavelength could more comprehensively treat vascular malformations than PDL alone. OBJECTIVE: To evaluate the safety and efficacy of the long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet (LP 1064-nm Nd:YAG) in conjunction with the 532-nm potassium titanyl phosphate (532-nm KTP) laser wavelengths for treatment of capillary venous and venous malformations. METHODS: In this retrospective single-center study, we queried patient records who underwent treatment with the 532-nm KTP and LP 1064-nm Nd:YAG laser wavelengths. A blinded panel of 3 physicians evaluated improvement in lesion color, elevation, texture, and overall architecture on a four-point scale: 0% to 25%; 26% to 50%, 51% to 75%, and 76% to 100%. RESULTS: Our cohort consisted of 23 cases. Sixteen cases had sufficient information for clinical assessment. Treatment number and parameters varied depending on lesion, skin type, and end point. Clinical assessment of treatment effectiveness revealed average scores of 51% to 75% improvement for color, elevation, texture, and overall architecture. CONCLUSION: This study illustrates that 2 wavelengths, 532-nm KTP to target superficial components and LP 1064-nm Nd:YAG for deeper components, can safely and effectively treat both capillary venous and venous malformations.

Venous leiomyosarcoma arising from the radiocephalic vein.

Vascular leiomyosarcoma is a very rare soft tissue neoplasma. We are reporting a vascular leiomyosarcoma case arising from an unusual site: the radiocephalic vein. Despite a poor prognosis, after surgery and radiotherapy, the patient was alive without signs of recurrence two years later.

Upregulation of Plasminogen Activator Inhibitor-1 in Irradiated Recipient Arteries and Veins from Free Tissue Transfer Reconstruction in Cancer Patients.

BACKGROUND: Clinical studies have shown that radiotherapy can induce vascular disease at the site of exposure but is usually not clinically evident until years after treatment. We have studied irradiated human arteries and veins to better understand the underlying biology in search of future treatments. The aim was to investigate whether radiotherapy contributed to a sustained expression of plasminogen activator inhibitor-1 (PAI-1) in human arteries and veins. METHODS: Irradiated arteries and veins were harvested, together with unirradiated control vessels, from patients undergoing free tissue transfer reconstruction at a median time of 90 weeks [5-650] following radiation exposure. Differential gene expression of PAI-1 was analysed, together with immunohistochemistry (IHC) and immunofluorescence (IF). RESULTS: PAI-1 gene expression was increased in both arteries (p = 0.012) and veins (p < 0.001) in irradiated compared to unirradiated control vessels. IHC and IF indicated that cells expressing PAI-1 were located in the adventitia of both arteries and veins and colocalized with cells positive for CD68, CD45, and α-SMA in arteries and with CD45 and α-SMA in veins. CONCLUSION: The current study shows a sustained upregulation of PAI-1 in both arteries and veins after exposure to ionizing radiation, indicating a chronic inflammation mainly in the adventitia. We believe that the results contribute to further understanding of radiation-induced vascular disease, where targeting PAI-1 may be a potential treatment.

Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.

Vascular injury after radiation exposure contributes to multiple types of tissue injury through a cascade of events. Some of the earliest consequences of radiation damage include increased vascular permeability and promotion of inflammation, which is partially manifested by increased leukocyte-endothelial (L/E) interactions. We describe herein a novel intravital imaging method to evaluate L/E interactions, as a function of shear stress, and vascular permeability at multiple time points after local irradiation to the ear. This model permitted analysis of quiescent vasculature that was not perturbed by any surgical manipulation prior to imaging. To evaluate the effects of radiation on vascular integrity, fluorescent dextran was injected intravenously and its extravasation in the extravascular space surrounding the ear vasculature was measured at days 3 and 7 after 6 Gy irradiation. The vascular permeability rate increased approximately twofold at both days 3 and 7 postirradiation ( P < 0.05). Leukocyte rolling, which is indicative of L/E interactions, was significantly increased in mice at 24 h postirradiation compared to that of nonirradiated mice. To assess our model, as a means for assessing vascular radioprotectants, we treated additional cohorts of mice with a thrombopoietin mimetic, TPOm (RWJ-800088). In addition to stimulating platelet formation, thrombopoietin can protect vasculature after several forms of injury. Thus, we hypothesized that TPOm would reduce vascular permeability and L/E adhesion after localized irradiation to the ear vasculature of mice. If TPOm reduced these consequences of radiation, it would validate the utility of our intravital imaging method. TPOm reduced radiation-induced vascular leakage to control levels at day 7. Furthermore, L/E cell interactions were also reduced in irradiated mice treated with TPOm, compared with mice receiving irradiation alone, particularly at high shear stress ( P = 0.03, Kruskal-Wallis). We conclude that the ear model is useful for monitoring quiescent normal tissue vascular injury after radiation exposure. Furthermore, the application of TPOm, for preventing early inflammatory response created by damage to vascular endothelium, suggests that this drug may prove useful in reducing toxicities from radiotherapy, which damage microvasculature that critically important to tissue function.

New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research.

The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague-Dawley rats (250-300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II-III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30-40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle.

Effects of pulsed electromagnetic fields on peripheral blood circulation in people with diabetes: A randomized controlled trial.

Cutaneous blood flow provides nourishment that plays an essential role in maintaining skin health. We examined the effects of pulsed electromagnetic fields (PEMFs) on cutaneous circulation of dorsal feet. Twenty-two patients with diabetes mellitus (DM) and 21 healthy control subjects were randomly allocated to receive either PEMFs or sham PEMFs (0.5 mT, 12 Hz, 30 min). Blood flow velocity and diameter of the small vein were examined by using ultrasound biomicroscopy; also, microcirculation at skin over the base of the 1st metatarsal bone (Flux1) and distal 1st phalange (Flux2) was measured by laser Doppler flowmetry before and after intervention. Results indicated that PEMFs produced significantly greater changes in blood flow velocity of the smallest observable vein than did sham PEMFs (both P < 0.05) in both types of subjects. However, no significant difference was found in changes of vein diameter, nor in Flux1 and Flux2, between PEMFs and sham PEMFs groups in subjects with or without DM. We hypothesized that PEMFs would increase blood flow velocity of the smallest observable vein in people with or without DM. Bioelectromagnetics. 37:290-297, 2016. © 2016 Wiley Periodicals, Inc.

Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.

PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.

Draining vein shielding in intracranial arteriovenous malformations during gamma-knife: a new way of preventing post gamma-knife edema and hemorrhage.

BACKGROUND: Following gamma knife (GK) therapy for intracranial arteriovenous malformations (AVMs), obliteration of the nidus occurs over several years. During this period, complications like rebleeding have been attributed to early draining vein occlusion. OBJECTIVE: To evaluate if shielding the draining vein(s) during GK therapy prevents early draining vein obliteration and complications following GK therapy. METHODS: This was a nonrandomized case-control study over 5 years (January 2009-February 2014) and included patients with intracranial AVM who underwent GK therapy at our center. All patients who underwent draining vein shielding by the senior author (D.A.) were included in the test group, and patients who did not undergo draining vein shielding were put in the control group. Patients were followed up for at least 6 months (and every 6 months thereafter) clinically as well as radiologically with computed tomography head scans/magnetic resonance imaging brain scans to check for postradiosurgery imaging (PRI) changes. RESULTS: One hundred eighty-five patients were included in this study, of which 96 were in the control group and 89 were in the test group. Both groups were well matched in demographics, comorbidities, adjuvant treatment, angioarchitecture, and radiation dosing. Because of shielding, the test group patients received significantly less radiation to the draining vein than the control group (P = .001). On follow-up, a significantly lower number of patients in the test group had new neurological deficits (P = .001), intracranial hemorrhage (P = .03), and PRI changes (P = .002). CONCLUSION: Shielding of the draining vein is a potent new strategy in minimizing PRI and hemorrhage as well as clinical deterioration following GK therapy for intracranial AVMs.

Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers.

BACKGROUND: Clinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. However, there is a lack of biological explanations in humans. We therefore examined human blood vessels exposed to radiotherapy and studied C-reactive protein (CRP) and pentraxin 3 (PTX3), a new marker for adverse cardiovascular outcome dependent on TNF- alpha (TNFα) or interleukin-1beta (IL-1ß) expression. METHODS: Pairs of irradiated and non-irradiated human conduit arteries and veins were harvested from the same patient during autologous free tissue transfer for cancer-reconstruction at a median time of 48 weeks after radiotherapy. Differential gene expression was studied using qRT-PCR, confirmed by immunohistochemistry and cellular origins determined by immunofluorescence. RESULTS: Gene expression in irradiated arteries compared to non-irradiated showed a consistent up-regulation of PTX3 in all patients and in a majority of veins (p < 0.001). Both TNFα and IL-1ß were increased in irradiated compared to non-irradiated arteries (p < 0.01) and IL-1ß correlated to the PTX3 expression (p = 0.017). Immunohistochemical and immunofluorescence staining confirmed an increased expression of PTX3 in endothelial cells, macrophages and smooth muscle cells. CONCLUSIONS: The sustained expression of PTX3 in arteries and veins tie biological evidence in humans to clinical studies and encourage further exploration of innate immunity in the pathogenesis of a radiation-induced vasculopathy.

[Role of optical properties of the venous wall for endovenous laser obliteration].

Presented herein are the results of studying the optical density of water, blood, and venous-wall tissue for various-wavelength laser radiation, with determining the peaks of absorption of radiation by the above-mentioned media. The absorption peaks in water and blood correspond to wavelengths of 1,450 and 1,935 nm, respectively. Peaks of absorption in the venous-wall tissue are within the intervals equaling 650-950 nm, 1,445-1,455 nm, and more than 1,900 nm. Also determined was the optical density of the veins for the most frequently used in clinical practice wavelengths, i. e. 1,030 and 1,470 nm, with the calculation of the portion of the absorbed energy depending on thickness of the layer of the absorbing substance. Based on the obtained findings, a conclusion was drawn on better utilization of the energy of one-and-a-half-micron range laser radiation and on its preferable use for endovenous laser obliteration (EVLO).

Periorbital rejuvenation: reticular vein treatment.

The safety profile of certain techniques, such as sclerotherapy, is questionable in a region as precarious as the periorbital region, where complications related to vision would be catastrophic. Other safe techniques such as phlebectomy can be performed with successful outcomes but are operator dependent, require a reasonable degree of technical ability, and can result in scarring and other complications. The aim of this article is to explore newer, laser-based treatment of these periorbital veins, discuss the physiology and the therapeutic efficacy, and better delineate the safety profile and evolution of the technique that has led to the present treatment paradigm.

[Endovasal obliteration of the main subcutaneous veins - a mechanism of action].

Active dissemination implementation of endovascular methods has during the past decade been a progressive tendency of the development of surgical treatment management of varicose disease.Amongst these methods, endovasal laser obliteration in Russia occupies the leading place. Despite widespread implementation of this method into clinical practice still there are neither common concepts on the mechanisms of action of laser energy, inducing lesions of the venous wall followed by obliteration, nor, consequently,criteria for administration thereof The search for an optimal method and mode of intravascular intervention is based on study-ing the mechanisms of the damaging action of laser energy on the venous wall. The article contains a literature review of the studies dedicated to investigating the mechanisms of action of endovasal methods of treatment for varicose disease.

[Comparative characteristics of laser-mediated and radiofrequency-powered thermal obliteration in varicose disease].

The article deals with a comparative analysis of the two most commonly used methods techniques of thermal ablation used for elimination of truncal varicosis in varicose disease, i. e., endovasal laser-mediated and radiofrequency-powered obliteration, underlining differences in the mechanisms of physical impact of the two competitive methods, clinical peculiarities of their application, as well as economic aspects of these interventions under the conditions of the present-day Russia.

Treatment of venous infraorbital dark circles using a long-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet laser.

BACKGROUND: Infraorbital dark circles are a common cosmetic problem with multiple causative factors and few studies into the different treatment options. OBJECTIVE: To assess the effectiveness and safety of long-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser therapy for infraorbital dark circles caused by visible prominent veins. PARTICIPANTS AND METHODS: Twenty-six patients with venous infraorbital dark circles were treated with a Nd:YAG laser (fluence, 130-140 J/cm(2) ; spot size, 6 mm) in double-pulse mode (pulse width, 6-10 ms; interpulse interval, 20 ms). Patients were examined 12 months after the final treatment. Results were ranked in five categories based on percentage clearance (5 = 100%, 4 = 75-99%, 3 = 50-74%, 2 = 25-49%, 1 ≤ 25% clearance). Patient satisfaction was ranked on a scale of 1 to 3 (1 = minimal improvement; 3 = completely satisfied), and pain was ranked on a scale of 1 to 10 (1 = mild pain; 10 = severe pain). RESULTS: Twenty-six patients completed the study. Objective improvement scores were 5 in all patients, and all patient satisfaction scores were 3. All patients tolerated the moderate pain (mean score 3.6). Transient erythema was observed in all patients. CONCLUSION: Long-pulsed 1,064-nm Nd:YAG-laser treatment appears effective and safe for the treatment of venous infraorbital dark circles and selectively removes visible prominent veins.

Optimal wavelengths for vein-selective photothermolysis.

BACKGROUND AND OBJECTIVE: Oxyhemoglobin (HbO(2)) has been regarded as the primary target chromophore for selective photothermolysis of vascular malformations. In theory, venous lesions might be better treated with wavelengths preferentially absorbed by deoxyhemoglobin (Hb). STUDY DESIGN/MATERIALS AND METHODS: Wavelength-dependent fluence thresholds for photocoagulation of whole human blood were determined in glass capillary samples with measured oxygen saturation levels. Pulsed dye lasers at 585, 590, 595, 600, 633 nm, a 694 nm ruby laser, a 755 nm alexandrite laser, and a 1,064 nm Nd:Yag laser were used, all with 1.5-3 milliseconds pulse width and similar exposure spot size. RESULTS: Selectivity (a lower fluence threshold) for venous blood was maximal at 694 nm, and significant at 595, 600, 633, and 755 nm. At 633 nm, a wavelength with strong relative absorption by metHb, selectivity for venous blood was much less than expected. The Nd:YAG laser at 1,064 nm showed significant selectivity for arterial blood. CONCLUSION: Preferential photocoagulation of venous blood is possible at wavelengths with a high Hb/HbO(2) absorption coefficient ratio. Laser-induced metHb may also affect wavelength-dependent selective photothermolysis. Venular malformations such as port wine stains could potentially be treated more selectively with ~630-780 nm sources. Nd:YAG laser pulses at 1,064 nm tend to affect arterial more than venous blood.

Effect of neoadjuvant chemoradiation and postoperative radiotherapy on expression of heat shock protein 70 (HSP70) in head and neck vessels.

BACKGROUND: Preoperative radiotherapy and chemotherapy in patients with head and neck cancer result in changes to the vessels that are used to construct microsurgical anastomoses. The aim of the study was to investigate quantitative changes and HSP70 expression of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses. METHODS: Of 20 patients included in this study five patients received neoadjuvant chemoradiation, another five received conventional radiotherapy and 10 patients where treated without previous radiotherapy. During surgical procedure, vessel specimens where obtained by the surgeon. Immunhistochemical staining of HSP70 was performed and quantitative measurement and evaluation of HSP70 was carried out. RESULTS: Conventional radiation and neoadjuvant chemoradiation revealed in a thickening of the intima layer of recipient vessels. A increased expression of HSP70 could be detected in the media layer of the recipient veins as well as in the transplant veins of patients treated with neoadjuvant chemoradiation. Radiation and chemoradiation decreased the HSP70 expression of the intima layer in recipient arteries. Conventional radiation led to a decrease of HSP70 expression in the media layer of recipient arteries. CONCLUSION: Our results showed that anticancer drugs can lead to a thickening of the intima layer of transplant and recipient veins and also increase the HSP70 expression in the media layer of the recipient vessels. In contrast, conventional radiation decreased the HSP70 expression in the intima layer of arteries and the media layer of recipient arteries and veins. Comparing these results with wall thickness, it was concluded, that high levels of HSP70 may prevent the intima layer of arteries and the media layer of vein from thickening.

[The carotid artery as recipient vessel: troubleshooting for free jejunal transfer after esophagectomy in preradiated patients]. / Gefäßanschluss an die A. carotis communis: Problemlösung bei freier Jejunuminterposition nach Ösophagektomie und Bestrahlung.

BACKGROUND: In the treatment of esophageal cancer neoadjuvant radiotherapy often leads to vascular damage of the usual recipient arteries for free jejunal transfer. End-to-side anastomosis to the carotid artery could be a potential alternative. PATIENTS AND METHODS: A total of 70 patients with locally advanced carcinoma of the esophagus underwent esophagectomy after neoadjuvant radiochemotherapy. In all patients reconstruction was carried out with a free jejunal transfer. Smaller vessels could be used for anastomoses in 54 of these patients and in 16 cases the jejunal flap artery was attached to the carotid artery. RESULTS: Out of 54 patients 9 (17%) with microvascular anastomoses to the smaller vessels needed surgical intervention for ischemia. In 16 patients with anastomosis to the carotid artery no significant failure of perfusion occurred. CONCLUSION: The carotid artery as recipient vessel in free jejunal transfer seems to be a safe therapeutic option for intestinal reconstruction of preradiated esophageal cancer with good functional results.

Endothelial activation with prothrombotic response in irradiated microvascular recipient veins.

BACKGROUND: Surgical wounds within previously irradiated tissues are common in reconstructive surgery and subject to an increased incidence of postoperative complications due to vascular dysfunction, including thrombosis in both microvascular anastomosis and the microcirculatory bed. However, there is no study that has described gene expression patterns in radiated human blood vessels. This study aims to determine if radiation can induce changes in gene expression that can promote thrombus formation in human microvascular recipient veins. METHODS: Paired biopsies from radiated recipient veins and non-radiated flap veins were simultaneously harvested from 15 patients during free-flap reconstruction, 4-215 weeks from termination of radiation. Radiated and non-radiated veins were compared using a custom-made Taqman(®) low-density array (TLDA) to analyse differential gene expression in a large number of genes involved in inflammation and coagulation. Results were confirmed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Results from TLDA indicate an acute increase of cytokines and leucocyte adhesion molecules related to activation of transcription factor nuclear factor kappa-B (NF-kB), confined to the first 3 months after radiotherapy treatment. Results were confirmed by RT-PCR and activity localised to the endothelium by immunohistochemistry. RT-PCR analyses of genes associated with coagulation showed sustained expression of plasminogen activator inhibitor-1 (PAI-1) in radiated veins. CONCLUSION: We found an acute inflammatory response with endothelial activation, followed by a sustained PAI-1 gene expression in irradiated microvascular recipient veins that can explain adverse effects years after radiation, such as microvascular occlusion and poor surgical wound healing. We believe that the results contribute to the search for therapeutic adjuncts to cope with the adverse effects of radiation therapy and strongly advocate postoperative, rather than preoperative, radiotherapy whenever possible.

Protecting venous structures during radiosurgery for parasagittal meningiomas.

Symptomatic edema is a potential complication of meningioma radiosurgery. Parasagittal meningiomas are at a particular risk for symptomatic edema, suggesting a role for a venous occlusive complication. The authors sought to develop a strategy to optimize CyberKnife stereotactic radiosurgical treatment parameters to reduce the irradiation of the peritumoral venous system. Multislice CT venography with 3D reconstructions was performed and coregistered with thin-section, contrast-enhanced, volumetric MR images. The tumor and critical volumes were contoured on the MR images. Venous anatomical details obtained from the CT venographic study were then exported onto the MR imaging and fused MR imaging-CT study. Target and critical structure volumes and dosimetric parameters obtained with this method were analyzed. The authors found that reducing the irradiation of veins that course along the surface of the meningioma, which may be at risk for radiation-induced occlusion, is feasible in parasagittal meningioma radiosurgery without compromising other treatment parameters including conformality, homogeneity, and target coverage. Long-term follow-up is needed to assess the clinical validity of this treatment strategy.