Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.

Frequent accesses to totally implanted vascular ports in pediatric oncology patients are associated with higher infection rates.

PURPOSE: Totally implanted vascular (TIVA) ports are used in children for repeated blood samples or intravenous treatments. We have recently published a prospective evaluation of surgical incidents and early complications associated with these devices. This work is the final part of the same study, assessing late complications over a follow-up of 2 yrs. METHODS: From January 2006 to January 2008, children older than 1 yr of age with a diagnosis of solid or blood cell malignancy were included. Insertion technique and care of the device were standardized. Every manipulation was prospectively recorded by specialized nurses. Obstruction was documented clinically. When bacteremia was suspected, routine central and peripheral blood cultures were drawn. RESULTS: Forty-five consecutive patients were enrolled in the study. Mean age at the time of the procedure was 8.5 yrs. There was no catheter-related infection within the first 4 weeks post-surgery. No device had to be removed because of infection or obstruction during follow-up. Frequent accesses to the port (=3 per day over a 10-day period) were associated with an 8-fold risk of infection. CONCLUSION: Insertion and use of TIVA devices were frequently associated with complications. No device had to be removed because of infection or obstruction over the follow-up period, although no prophylactic antibiotic agent was used. Restrictive use of antibiotics may prevent opportunistic infection. Frequent access to the device was significantly associated with line infection (odds ratio=8.43). No risk factor was identified for obstruction which occurred at a rate of 5.3 per 10,000 accesses.

Vascular postpneumonectomy syndrome: inferior vena cava and pulmonary vein compression as unusual cause for platypnea-orthodeoxia following pneumonectomy

Background: Excessive mediastinal shift into the vacated thoracic cavity after pneumonectomy can result in dyspnea without hypoxemia by compression of the tracheobronchial tree, a phenomenon called postpneumonectomy syndrome. More rarely hypoxemia in upright position (platypnea-orthodeoxia syndrome, POS) after pneumonectomy can result from re-opening of an atrial right-to-left shunt through a patent foramen ovale (PFO) due to mediastinal distorsion. Review of literature also shows a unique report of pulmonary veins stenosis resulting in POS without intracardiac shunt after pneumonectomy. Methods: We report the case of a 32-year-old woman who presented POS 6 months after right pneumonectomy for destroyed lung post tuberculosis. Results: The patient described severe dyspnea disappearing when lying. SpO2 decreased from 94% when lying to 60% sitting. Transthoracic echocardiography (TTE) suspected a possible PFO. We first tried to highlight clinical repercussions of PFO by noninvasive exams. Hyperoxia shunt quantification was not tolerated because of increased dyspnea in sitting position. Contrast bubbles TTE was difficult because of the important mediastinal shift but identified only rare left heart bubbles with/without Valsalva both in lying and sitting position, excluding a significant right-to-left shunt. A lung perfusion scintigraphy (injection while sitting) confirmed the absence of systemic isotope uptake. Computed tomographic pulmonary angiography (angio-CT) revealed a stretched but not stenosed left main bronchus, while the shift of the heart into the right cavity was major. Pulmonary angiography did not show embolism but revealed compression of the inferior vena cava (IVC) with impaired venous return to the right heart, as well as compression of the left pulmonary veins. There was no arteriovenous shunt. Cardiac MRI showed torsion of IVC at the level of the diaphragm, and strong atrial contraction contributing to a passive filling of the RV, while the right ventricle was normal. Right catheterism showed major hemodynamic disturbances with negative diastolic pressure in right heart cavities (atrium -12 mm Hg ventricle pressure -7 mm Hg). SaO2 measured in the pulmonary artery decreased from 58% when lying to 45% sitting. Conclusion: We described here an exceedingly rare and complex mechanism explaining POS after right pneumonectomy. Mediastinal repositioning with a silicone breast implant of appropriate size has been scheduled.

Assessment of vascular invasion by bone and soft tissue tumours of the limbs: usefulness of MDCT angiography.

OBJECTIVE: To evaluate the accuracy of computed tomography angiography (CTA) in predicting arterial encasement by limb tumours, by comparing CTA with surgical findings (gold standard). METHODS: Preoperative CTA images of 55 arteries in 48 patients were assessed for arterial status: cross-sectional CTA images were scored as showing a fat plane between artery and tumour (score 0), slight contact between artery and tumour (score 1), partial arterial encasement (score 2) or total arterial encasement (score 3). Reformatted CTA images were assessed for arterial displacement, rigid wall, stenosis or occlusion. At surgery, arteries were classified as free or surgically encased; 45 arteries were free and 10 were surgically encased. RESULTS: Multivariate logistic regression identified the axial CTA score as a relevant predictor for arterial encasement and subsequent vascular intervention during surgery. All sites where CTA showed a fat plane between the tumour and the artery were classified as free at surgery (n = 28/28). The sensitivity of total arterial encasement on CTA (score 3) was 90%, specificity 93%, accuracy 93% and positive likelihood ratio 13.5. CONCLUSION: CTA evidence of total arterial encasement is a highly specific indication of arterial encasement. The presence of fat between the tumour and the artery on CTA rules out arterial involvement at surgery.

Transobturator surgery for female stress incontinence: a comparative anatomical study of outside-in vs inside-out techniques.

OBJECTIVE To assess the specific risks of injury to neural and vascular structures inherent in two approaches to transobturator surgery for inserting a suburethral sling, i.e. the outside-in (standard technique) and inside-out approaches. MATERIALS AND METHODS The study comprised seven cadavers, providing 14 obturator regions. Five specimens had a tape inserted outside-in on one side, and inside-out on the other; of the remaining two cadavers, one had an inside-out tape and one an outside-in tape, bilaterally. After tape insertion, the cadavers were dissected. Particular attention was paid to the distances between the tape and the deep external pudendal vessels, and between the tape and the posterior branch of the obturator nerve. RESULTS With the inside-out technique, the safety margins were reduced, and the external pudendal vessels and the posterior branch of the obturator nerve were at greater risk of injury. CONCLUSION The two techniques are not equivalent, with a lower risk of injury to vascular and nerve structures with the outside-in technique.

Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.

PURPOSE: Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs. We have tested the hypothesis that bone marrow-derived MSCs (BM-MSCs) stabilizes AAAs in a rat model. MATERIAL AND METHODS: Rat Fischer 344 BM-MSCs were isolated by plastic adhesion and seeded endovascularly in experimental AAAs using xenograft obtained from guinea pig. Culture medium without cells was used as control group. The main criteria was the variation of the aortic diameter at one week and four weeks. We evaluated the impact of cells seeding on inflammatory response by immunohistochemistry combined with RT-PCR on MMP9 and TIMP1 at one week. We evaluated the healing process by immunohistochemistry at 4 weeks. RESULTS: The endovascular seeding of BM-MSCs decreased AAA diameter expansion more powerfully than VSMCs or culture medium infusion (6.5% ± 9.7, 25.5% ± 17.2 and 53.4% ± 14.4; p = .007, respectively). This result was sustained at 4 weeks. BM-MSCs decreased expression of MMP-9 and infiltration by macrophages (4.7 ± 2.3 vs. 14.6 ± 6.4 mm(2) respectively; p = .015), increased Tissue Inhibitor Metallo Proteinase-1 (TIMP-1), compared to culture medium infusion. BM-MSCs induced formation of a neo-aortic tissue rich in SM-alpha active positive cells (22.2 ± 2.7 vs. 115.6 ± 30.4 cells/surface units, p = .007) surrounded by a dense collagen and elastin network covered by luminal endothelial cells. CONCLUSIONS: We have shown in this rat model of AAA that BM-MSCs exert a specialized function in arterial regeneration that transcends that of mature mesenchymal cells. Our observation identifies a population of cells easy to isolate and to expand for therapeutic interventions based on catheter-driven cell therapy.

Anévrismes complexes de l'aorte abdominale: la chirurgie ouverte est-elle obsolète [The complex aortic abdominal aneurysm: is open surgery old fashion?].

Open surgery is still the main treatment of complex abdominal aortic aneurysm. Nevertheless, this approach is associated with major complications and high mortality rate. Therefore the fenestrated endograft has been used to treat the juxtarenal aneurysms. Unfortunately, no randomised controlled study is available to assess the efficacy of such devices. Moreover, the costs are still prohibitive to generalise this approach. Alternative treatments such as chimney or sandwich technique are being evaluated in order to avoid theses disadvantages. The aim of this paper is to present the endovascular approach to treat juxtarenal aneurysm and to emphasize that this option should be used only by highly specialized vascular centres.

Laser treatment of 13 benign oral vascular lesions by three different surgical techniques

Objectives: Benign Oral Vascular Lesions (BOVLs) are a group of vascular diseases characterized by congenital, inflammatory or neoplastic vascular dilations clinically evidenced as more or less wide masses of commonly dark bluish color. If traumatized BOVLs are characterized by a great risk of hemorrhage and their treatment usually requires great caution to prevent massive bleeding. In the last decades lasers have dramatically changed the way of treatment of BOVLs permitting the application of even peculiar techniques that gave interesting advantages in their management reducing hemorrhage risks. The aim of this study was to evaluate the capabilities and disadvantages of three laser assisted techniques in the management of BOVLs. Study design: In this study 13 BOVLs were treated by three different laser techniques: the traditional excisional biopsy (EB), and two less invasive techniques, the transmucosal thermocoagulation (TMT) and the intralesional photocoagulation (ILP). Two different laser devices were adopted in the study: a KTP laser (DEKA, Florence, Italy, 532nm) and a GaAlAs laser (Laser Innovation, Castelgandolfo, Italy, 808nm) selected since their great effectiveness on hemoglobin. Results: In each case, lasers permitted safe treatments of BOVLs without hemorrhages, both during the intervention and in the post-operative period. The minimally invasive techniques (TMT and ILP) permitted even the safe resolution of big lesions without tissue loss. Conclusions: Laser devices confirm to be the gold standard in BOVLs treatment, permitting even the introduction of minimal invasive surgery principles and reducing the risks of hemorrhage typical of these neoplasms. As usual in laser surgery, it is necessary a clear knowledge of the devices and of the laser-tissue interaction to optimize the results reducing risks and disadvantages

Investigations of a thermosensitive gel to temporarily occlude crural arteries in femoro-distal bypass surgery.

OBJECTIVES: Long occlusions in calcified crural arteries are a major cause of endovascular technical failure in patients with critical limb ischaemia. Therefore, distal bypasses are mainly performed in patients with heavily calcified arteries and with consequently delicate clamping. A new reverse thermosensitive polymer (RTP) is an alternative option to occlude target vessels. The aim of the study is to report our technical experience with RTP and to assess its safety and efficiency to temporarily occlude small calcified arteries during anastomosis time. METHODS: Between July 2010 and December 2011, we used RTP to occlude crural arteries in 20 consecutive patients with 20 venous distal bypasses. We recorded several operative parameters, such as volume of injected RTP, duration of occlusion and anastomotic time. Quality of occlusion was subjectively evaluated. Routine on-table angiography was performed to search for plug emboli. Primary patency, limb salvage and survival rates were reported at 6 months. RESULTS: In all patients, crural artery occlusion was achieved with the RTP without the use of an adjunct occlusion device. Mean volume of RTP used was 0.3 ml proximally and 0.25 ml distally. Mean duration of occlusion was 14.4 ± 4.5 min, while completion of the distal anastomosis lasted 13.4 ± 4.3 min. Quality of occlusion was judged as excellent in eight cases and good in 12 cases. Residual plugs were observed in two patients and removed with an embolectomy catheter, before we amended the technique for dissolution of RTP. At 6 months, primary patency rate was 75% but limb salvage rate was 87.5%. The 30-day mortality rate was 10%. CONCLUSIONS: This study shows that RTP is safe when properly dissolved and effective to occlude small calcified arteries for completion of distal anastomosis.

Tratamento endovascular de dissecção crônica toracoabdominal complicada com aneurisma torácico, mediante implante de endoprótese vascular

Our objective is to report a case of a patient with a descending thoracic aortic aneurysm and chronic aortic dissection, who was submitted to an endovascular treatment. A 68-year-old male with coronary artery disease and hypertension, with no history of trauma, diabetes or smoking. He had myocardial infarction ten years ago. Under general anesthesia, the left femoral artery was surgically exposed and the left braquial artery was catheterized with a "pigtail" catheter, under Seldinger technique. The proximal 46mm/Æ and distal 34mm/Æ stent-graft was placed just distal to the origen of the left subclavian artery. Control arteriography showed that the lesion was completely excluded. The patient was discharged seven days after the surgery, when a computed tomographic control, was performed showing a sustained aneurysm exclusion and a satisfactory endovascular position.

Damage control surgery: it's evolution over the last 20 years

In less than twenty years, what began as a concept for the treatment of exsanguinating truncal trauma patients has become the primary treatment model for numerous emergent, life threatening surgical conditions incapable of tolerating traditional methods. Its core concepts are relative straightforward and simple in nature: first, proper identification of the patient who is in need of following this paradigm; second, truncation of the initial surgical procedure to the minimal necessary operation; third, aggressive, focused resuscitation in the intensive care unit; fourth, definitive care only once the patient is optimized to tolerate the procedure. These simple underlying principles can be molded to a variety of emergencies, from its original application in combined major vascular and visceral trauma to the septic abdomen and orthopedics. A host of new resuscitation strategies and technologies have been developed over the past two decades, from permissive hypotension and damage control resuscitation to advanced ventilators and hemostatic agents, which have allowed for a more focused resuscitation, allowing some of the morbidity of this model to be reduced. The combination of the simple, malleable paradigm along with better understanding of resuscitation has proven to be a potent blend. As such, what was once an almost lethal injury (combined vascular and visceral injury) has become a survivable one.

Vascular changes after cardiopulmonary bypass and ischemic cardiac arrest: roles of nitric oxide synthase and cyclooxygenase

Cardiac surgery involving ischemic arrest and extracorporeal circulation is often associated with alterations in vascular reactivity and permeability due to changes in the expression and activity of isoforms of nitric oxide synthase and cyclooxygenase. These inflammatory changes may manifest as systemic hypotension, coronary spasm or contraction, myocardial failure, and dysfunction of the lungs, gut, brain and other organs. In addition, endothelial dysfunction may increase the occurrence of late cardiac events such as graft thrombosis and myocardial infarction. These vascular changes may lead to increased mortality and morbidity and markedly lengthen the time of hospitalization and cost of cardiac surgery. Developing a better understanding of the vascular changes operating through nitric oxide synthase and cyclooxygenase may improve the care and help decrease the cost of cardiovascular operations.

Lesiones abiertas del plexo braquial con compromiso vascular concomitante. Revisión sistemática de la literatura.

La presente investigación, intenta generar un impacto positivo dentro del ámbito médico-quirúrgico, ya que se espera que la revisión de la literatura genere mayor conocimiento sobre el manejo de las lesiones del plexo braquial con lesión vascular concomitante, ocasionada mediante un trauma abierto por herida causada por arma corto punzante, y con base en esto proponer una guía de manejo que se pueda aplicar en el día a día de todos aquellos especialistas quirúrgicos y no quirúrgicos para el tratamiento de dicha lesión. Es importante resaltar la dificultad metodológica presentada ante la poca validez de los estudios seleccionados, a pesar de que se aplicaron normas estrictas para la selección de los artículos. Las lesiones vasculares y nerviosas concomitantes del miembro superior no solo comprometen la viabilidad de la extremidad sino que además se constituyen en lesiones con secuelas severas desde el punto de vista funcional para el paciente. No se ha establecido un protocolo de manejo de estas lesiones. Los estudios realizados carecen de metodología adecuada de evaluación tanto en el momento de ingreso del paciente a urgencias como en su preoperatorio, postoperario y en las evaluaciones de los resultados funcionales de la extremidad una vez superada la lesión inicial. No hay una evolución consignada en la literatura con respecto al manejo integral de estos pacientes, que nos permita discernir con respecto al momento adecuado de la reparación nervios. El establecimiento de una guía clínica para cirujanos vasculares y cirujanos de mano para el manejo integral de este tipo de lesiones es apremiante. Los costos de tratamiento y rehabilitación de este tipo de pacientes son indiscutiblemente elevados desde todo punto de vista, pero es definitivo que el resultado funcional es mejor cuando se establece un manejo sistemático que incluya el manejo vascular y el manejo de la lesión neurológica de una forma integral.

Manejo de lesiones abiertas del plexo braquial con compromiso vascular concomitante. Revisión sistemática de la literatura

El manejo de las lesiones de plejo braquial ha sido ampliamente discutido e investigado, especialmente en las lesiones cerradas por tracción. Las lesiones abiertas con compromiso vascular, muchas veces comprometen la viabilidad de la extremidad o la vida del paciente; son de difícil manejo con prioridades distintas, tiempos de establecimiento de los procedimientos que varían respecto a los hallazgos con resultados funcionales pobres por el diagnostico tardío de la lesión nerviosa. Se plantean interrogantes desde el punto de vista vascular y de la lesión nerviosa. se realiza una revisión sistemática de la literatura, encontrando puntos importantes con respecto a la exploración, el momento de la reparación nerviosa pero sin establecer resultados funcionales claros ante la deficiencia metodológica de los estudios encontrados.

Short-term induction of thrombocytopenia delays periodontal healing in rats with periodontal disease: participation of endostatin and vascular endothelial growth factor

Background and Objective: Platelets contain factors, including VEGF and endostatin, that can modulate the healing process. We evaluated the effects of severe thrombocytopenia on periodontal healing in rats and determined the contribution of VEGF and endostatin to the healing process. Material and Methods: Rats were distributed into three test groups and two control groups. Cotton ligatures were placed at the gingival margin level of the lower first molar in the test groups. Sham-operated rats and rats in one of the periodontitis groups were killed 15 days later. Rats in the remaining two periodontitis groups had the ligatures removed in order to study the spontaneous recovery from the periodontal disease 15 days later, and these rats were treated with rabbit antiplatelet serum, in order to induce thrombocytopenia, or normal rabbit serum. An additional group without ligatures received antiplatet serum in the same period. Results: After ligature removal, rats treated with normal rabbit serum showed reduced myeloperoxidase activity, decreased alveolar bone loss and increased numbers of blood vessels. Thrombocytopenia caused a delay in alveolar bone regeneration, a decrease in the number of vessels and a modest decrease in myeloperoxidase activity. In the rats with periodontitis, serum endostatin concentrations were slightly decreased and serum VEGF remained unchanged compared with sham-operated animals. After ligature removal, a significant VEGF increase and endostatin decrease were observed in the rats treated with normal rabbit serum. Thrombocytopenia led to a dramatic fall in both VEGF and endostatin concentrations. Conclusion: Thrombocytopenia leads to a delay of periodontal healing in the situation of experimental periodontitis, which might be mediated in part by a decrease in the serum concentration of VEGF and endostatin derived from the platelets. However, other factors derived from the platelets may also have contributed to a delay of periodontal healing in the rats with thrombocytopenia.