Study on the efficacy of surgery of the superficial venous system and of compression therapy at early stages of chronic venous disease for the prevention of chronic venous ulceration.

The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59·64%) (Group A) fully adherent to protocols; 848 patients (21·48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10·95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7·93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3·23-4.79%), with no statistical significance (P = 0·1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings.

Updates in Pathophysiology, Diagnosis and Management of Takayasu Arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare, systemic, inflammatory vasculitis of granulomatous nature, and still of unknown etiology. It mainly involves the aorta and its major branches and is more commonly seen in women of childbearing age and Asians. TA leads to stenosis, occlusion, or aneurysmal degeneration of large arteries, and its pathogenesis seems to be mainly due to an abnormal cell-mediated immunity, although other molecular and genetic abnormalities may contribute. The diagnosis and treatments lie on clinical and arteriographic findings. Because of its fluctuating course, both clinical scores and biomarkers are currently evaluated. The aim of this review is to report a comprehensive and methodologically robust state of the art about Takayasu arteritis, including the latest data and evidences in the definition, epidemiology, pathogenesis and etiology, clinical manifestations and classification, diagnosis, assessment of disease activity and progression, biomarkers, and treatment. METHODS: We searched all publications addressing definition, epidemiology, pathogenesis, etiology, classification, diagnosis, biomarkers, and treatment of TA. Randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. PubMed and Scopus were searched from August 2010 to November 2015. RESULTS: Of the 3,056 records found, 267 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 169 articles because of the following reasons: (1) no innovative or important content; (2) no multivariable analysis; (3) insufficient data; (4) no clear potential biases or strategies to solve them; (5) no clear end-points; and (6) inconsistent or arbitrary conclusions. The final set included 98 articles. CONCLUSIONS: This review presents the last updates in all fields of Takayasu arteritis. Still today, large areas of TA pathogenesis and disease-activity assessment need to be further investigated to better treat patients with TA.

Surgical treatment of recidivist lymphedema.

Lymphedema is a chronic disease with a progressively ingravescent evolvement and an appearance of recurrent complications of acute lymphangitic type; in nature it is mostly erysipeloid and responsible for a further rapid increase in the volume and consistency of edema. The purpose of this work is to present our experience in the minimally invasive treatment for recurrence of lymphedema; adapting techniques performed in the past which included large fasciotomy with devastating results cosmetically; but these techniques have been proposed again by the use of endoscopic equipment borrowed from the advanced laparoscopy surgery, which allows a monoskin access of about one cm.

Matrix metalloproteinases and risk stratification in patients undergoing surgical revascularisation for critical limb ischaemia.

Critical limb ischaemia (CLI) is the most advanced form of peripheral artery disease (PAD) and it is often associated with foot gangrene, which may lead to major amputation of lower limbs, and also with a higher risk of death due to fatal cardiovascular events. Matrix metalloproteinases (MMPs) seem to be involved in atherosclerosis, PAD and CLI. Aim of this study was to evaluate variations in MMP serum levels in patients affected by CLI, before and after lower limb surgical revascularisation through prosthetic or venous bypass. A total of 29 patients (7 females and 22 males, mean age 73·4 years, range 65-83 years) suffering from CLI and submitted to lower extremity bypass (LEB) in our Institution were recruited. Seven patients (group I) underwent LEB using synthetic polytetrafluoroethylene (PTFE) graft material and 22 patients (group II) underwent LEB using autogenous veins. Moreover, 30 healthy age-sex-matched subjects were also enrolled as controls (group III). We documented significantly higher serum MMPs levels (P < 0·01) in patients with CLI (groups I and II) with respect to control group (group III). Finally, five patients with CLI (17·2%) showed poor outcomes (major amputations or death), and enzyme-linked immunosorbent assay (ELISA) test showed very high levels of MMP-1 and MMP-8. MMP serum levels seem to be able to predict the clinical outcomes of patients with CLI.

Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers.

INTRODUCTION: An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids. METHODS: In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers). RESULTS: We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids. CONCLUSION: These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis.

The role of adult tissue-derived stem cells in chronic leg ulcers: a systematic review focused on tissue regeneration medicine.

Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that represent an important cause of morbidity and public cost in western countries. Because of their common recurrence after conventional managements and increasing prevalence due to an ageing population, newer approaches are needed. Over the last decade, the research has been focused on innovative treatment strategies, including stem-cell-based therapies. After the initial interest in embryonic pluripotent cells, several different types of adult stem cells have been studied because of ethical issues. Specific types of adult stem cells have shown a high potentiality in tissue healing, in both in vitro and in vivo studies. Aim of this review is to clearly report the newest insights on tissue regeneration medicine, with particular regard for chronic leg ulcers.

Biomarkers in post-reperfusion syndrome after acute lower limb ischaemia.

Ischaemia reperfusion (I/R) injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischaemia. Matrix metalloproteinases (MMPs), neutrophil gelatinase-associated lipocalin (NGAL) and cytokines are biomarkers involved in several vascular complications. The aim of this study was to evaluate the role of MMPs, NGAL and inflammatory cytokines in I/R syndrome. We conducted an open label, multicentric, parallel group study, between January 2010 and December 2013. Patients with acute limb ischaemia were enrolled in this study and were divided into two groups: (i) those subjected to fasciotomy and (ii) those not subjected to fasciotomy, according to the onset of compartment syndrome. Plasma and tissue values of MMPs and NGAL as well as plasma cytokines were evaluated. MMPs, NGAL and cytokine levels were higher in patients with compartment syndrome. Biomarkers evaluated in this study may be used in the future as predictors of I/R injury severity and its possible evolution towards post-reperfusion syndrome.

VAC therapy for the treatment of complex wounds after cardio-thoracic surgery.

The aim of this study is to report our experience about the treatment of complex sternal and thoracic wounds following cardiothoracic surgery, using vacuum-assisted closure (VAC therapy. Twelve patients presenting with sternal (five cases) and thoracic (seven cases) wounds that were difficult to heal were treated through VAC therapy after the first surgical debridement. The duration of VAC application ranged from 12 to 36 days with an average hospital stay of 24·6 ± 11·4 days. During a mean follow-up of 12 months, we observed complete wound healing in seven cases (58·3%), in an average period of 25·5 ± 14·3 days; one patient died during follow-up, two patients were lost to follow-up and two patients required definitive surgical closure of the wound cavity. In conclusion, VAC therapy promotes faster wound healing, with shorter hospital stay and subsequent lesser in-hospital cost, reducing the mortality rate in the long run. It also promotes early rehabilitation and alleviates the need for a second procedure, thus improving patient satisfaction, with minimal discomfort or inconvenience.

Effectiveness of prostaglandin E1 in patients with mixed arterial and venous ulcers of the lower limbs.

Mixed arterial and venous ulcers of the lower limbs are present in around 15-30% of patients with chronic venous ulcers (CVUs) and are considered difficult-to-heal wounds. The aim of this study was to evaluate the results of the treatment of mixed arterial and venous ulcers of the lower limbs with prostaglandin E1 (PGE1) infusion. This study was carried out in 48 consecutive patients. Patients who showed intolerability to PGE1, and patients with peripheral neuropathy, blood or systemic diseases, malignancy and acute wound infections or necrotic tissue on the wound bed were excluded. The patients were separated at random into two main groups: group I (25 patients) received standard treatment and PGE1 infusion. Group II (23 patients) received only standard treatment. Pre-treatment data indicated the area of ulceration. The number of healed ulcers and the variation in the area of ulceration were considered as endpoints. The endpoints were noticed after 120 days from the beginning of treatment. Healing occurred in 80% of limbs of group I and in 52·2% of limbs of group II patients. The average reduction in area was 92% versus 60% in patients of group I and II, respectively. During the whole treatment period, the incidence of adverse events was 8% in group I: there was one case of headache and one case of headache and hypotension combined. No side effects were recorded in patients of group II. In conclusion, PGE1 infusion is a determinant in the reduction of the healing time of mixed ulcers of the lower limbs.

VAC therapy to promote wound healing after surgical revascularisation for critical lower limb ischaemia.

Vacuum-assisted closure (VAC) therapy is a new emerging non-invasive system in wound care, which speeds up wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates, and facilitating the removal of bacteria from the wound. The application of sub-atmospheric pressure on the lesions seems to alter the cytoskeleton of the cells on the wound bed, triggering a cascade of intracellular signals that increase the rate of cell division and subsequent formation of granulation tissue. The aim of this study is to analyse the results of VAC therapy used as an adjuvant therapy for the treatment of foot wounds in patients affected by critical limb ischaemia (CLI) (Rutherford 6 class) after distal surgical revascularisation, to promote and accelerate the healing of ulcers. Twenty-nine patients (20 males, 9 females; mean age 68·4) affected by CLI of Rutherford 6 class, after surgical revascularisation of the lower limb, underwent VAC therapy in order to speed up wound healing. Complete wound healing was achieved in 19 patients (65·51%), in an average period of 45·4 ± 25·6 days. VAC therapy is a valid aid, after surgical revascularisation, to achieve rapid healing of foot lesions in patients with CLI.

Adjuvant spinal cord stimulation improves wound healing of peripheral tissue loss due to steal syndrome of the hand: clinical challenge treating a difficult case.

Hand ischaemia due to arterial steal syndrome is an infrequent, but potentially serious complication of arteriovenous fistula (AVF) for haemodialysis. We present a case of hand ischaemia caused by steal syndrome in a 69-year-old haemodialysis patient, 10 months after a brachiobasilic fistula creation. The patient underwent multiple operations without resolution of hand pain and tissue loss. The implantation of an adjuvant cervical spinal cord stimulator allowed the patient to obtain complete hand pain relief and wound healing. Probably, the diffuse microangiopathy typical of haemodialysis patients could be responsible for the persistence of ischaemic signs and symptoms after a surgical revascularisation. The effect of sympathetic blockade and the subsequent improvement of the arterial blood flow and tissue oxygenation because of spinal cord stimulation (SCS) can be useful to achieve complete ischaemic pain relief in order to enhance wound healing and to limit the tissue loss. In conclusion, the association of cervical spinal cord stimulation and surgical revascularisation could represent a valid option to treat a critical upper limb ischaemia following steal syndrome due to AVF.

Effects of a new nutraceutical substance on clinical and molecular parameters in patients with chronic venous ulceration.

Pathophysiological events involved in the onset of chronic venous ulceration (CVU) are inflammation, activation of polymorphonucleates (PMNs) and secretion of proteases such as matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) that is a support for vascular and tissutal wall. MMPs, neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory cytokines are overexpressed in CVUs and they could play a central role in pathophysiological mechanisms of skin lesion and delayed wound healing. Bioflavonoids, such as diosmin and other compounds, appear to have several provessel function activities including anti-inflammatory, antioxidant and phlebotonic effects and are widely used in the treatment of chronic venous disease (CVD)-related problems. In this article, we evaluated the effects of Axaven(®) , a new nutraceutical on both clinical and molecular parameters in patients with CVUs. During the study period, 83 patients with CVUs of both sexes were enrolled and divided into two groups: group A (treated group): 25 females and 19 males (median age is 67·7 years) received standard treatment (compression therapy and surgical correction of superficial venous incompetence) + Axaven(®) once a day for 8 months as adjunctive treatment. Group B (control group): 24 females and 15 males (median age is 65·2 years) were treated only with basic treatment according to their clinical conditions. In our study, the administration of Axaven(®) in patients with CVUs was able to decrease inflammatory cytokines, MMPs and NGAL, inducing an improvement of both symptoms with an increase of the speed of wound healing.

Extreme distal bypass to improve wound healing in Buerger's disease.

Thromboangiitis obliterans or Buerger's disease is a rare non-atherosclerotic segmental inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities, and generally affects young tobacco smokers. A 53-year-old man was found to have critical ischaemia of his left lower limb with foot gangrene. He underwent extremely distal surgical revascularisation using a great saphenous vein bypass graft. The choice of a very distal artery as run-off vessel promoted a faster wound healing and pain relief, with improvement in quality of life.

Endovascular repair for acute traumatic transection of the descending thoracic aorta: experience of a single centre with a 12-years follow up.

BACKGROUND: Most blunt aortic injuries occur in the proximal proximal descending aorta causing acute transection of this vessel. Generally, surgical repair of the ruptured segment of aorta is associated with high rates of morbidity and mortality and in this view endovascular treatment seems to be a valid and safer alternative. Aim of this article is to review our experience with endovascular approach for the treatment of acute traumatic rupture of descending thoracic aorta. METHODS: From April 2002 to November 2014, 11 patients (9 males and 2 females) were referred to our Department with a diagnosis of acute transection of thoracic aorta. Following preoperative Computed Tomography (CT) evaluation, thoracic endovascular aortic repair (TEVAR) with left subclavian artery coverage was performed. Follow-up consisted clinical and instrumental (CT, Duplex ultrasound) controls at discharge, 1, 3 and 6 months and yearly thereafter. RESULTS: At 12-year follow up, the overall survival for the entire patients cohort was 100 %, no major or minor neurological complications and no episode of left arm claudication occurred. Cardiovascular, respiratory and bleeding complications, in the early period, was represented by minor, non fatal events. No stent graft failure, collapse, leak or distal migration were detected at CT scan during the entire follow up period. CONCLUSIONS: According to our experience, despite the small number of patient population, TEVAR procedure with with left subclavian artery coverage, performed in emergency settings, seems to provide excellent long term results. TRIALS REGISTRATION: The protocol was registered at a public trials registry, www.clinicaltrials.gov (trial identifier NCT02376998 ).

Absorbable suture material in carotid surgery.

BACKGROUND: Absorbable sutures are not generally accepted by most vascular surgeons for the fear of breakage of the suture line and the risk of aneurysmal formation, except in cases of paediatric surgery or in case of infections. Aim of this study is to provide evidence of safety and efficacy of the use of absorbable suture materials in carotid surgery. PATIENTS AND METHODS: In an 11 year period, 1126 patients (659 male [58.5%], 467 female [41.5%], median age 72) underwent carotid endarterectomy for carotid stenosis by either conventional with primary closure (cCEA) or eversion (eCEA) techniques. Patients were randomised into two groups according to the type of suture material used. In Group A, absorbable suture material (polyglycolic acid) was used and in Group B non-absorbable suture material (polypropylene) was used. Primary end-point was to compare severe restenosis and aneurysmal formation rates between the two groups of patients. For statistical analysis only cases with a minimum period of follow-up of 12 months were considered. RESULTS: A total of 868 surgical procedures were considered for data analysis. Median follow-up was 6 years (range 1-10 years). The rate of postoperative complications was better for group A for both cCEA and eCEA procedures: 3.5% and 2.0% for group A, respectively, and 11.8% and 12.9% for group B, respectively. CONCLUSIONS: In carotid surgery, the use of absorbable suture material seems to be safe and effective and with a general lower complications rate compared to the use of non-absorbable materials.

Venous aneurysm complicating arteriovenous fistula access and matrix metalloproteinases.

INTRODUCTION: An arteriovenous fistula (AVF) for placed for hemodialysis may be burdened by one particular complication-the formation of a venous aneurysm. It has been shown that matrix metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL) could represent markers of disease in both venous and arterial vessels. MATERIALS AND METHODS: This case study reports a rare case of enormous venous aneurysm-correlated MMP and NGAL levels in a woman with an AVF. RESULTS: Significantly higher levels of plasma MMP-1, MMP-8, MMP-9, and NGAL were detected in this patient during aneurysmal evaluation before the surgery; these levels significantly decreased 1, 3 and 6 months after surgery. CONCLUSION: MMP and NGAL levels could represent a marker of aneurysmal disease, and their plasma evaluation could help physicians to stratify the risk of complications in patients with an AVF.

The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms.

INTRODUCTION: An association between arterial aneurysms and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between the levels of MMPs and NGAL and arterial aneurysms. METHODS: In a multicenter, open-label, parallel groups, prospective study, patients with aneurysmal disease were divided into 2 groups: Group I (with ruptured aneurysm) and group II (with nonruptured aneurysm). Healthy volunteer patients were also enrolled and represented the control group (group III). RESULTS: We enrolled 307 patients (107 in group I and 200 in group II) with arterial aneurysm: 49 popliteal, 31 common femoral, 2 superficial femoral, 29 common iliac artery, 3 common carotid, and 193 abdominal aorta. Finally, 11 healthy volunteer patients (9 males and 2 females; age range, 40-70 years; median 56) were enrolled in group III. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMP-9 and NGAL in all patients with ruptured aneurysms, both central and peripheral aneurysms, and in the aneurismal vessels. CONCLUSION: These results provide potentially important insights to the understanding of the natural history of arterial aneurysms. MMPs and NGAL play a role in development of arterial aneurysms and may represent molecular markers for the prevention of aneurysmal rupture.

Concomitant aortic leiomyosarcoma and takayasu arteritis in a 55-year-old male patient.

Takayasu arteritis is a form of large vessel granulomatous vasculitis affecting often young or middle-aged women, especially of Asian descent. It mainly affects the aorta and its branches. Primary malignancies, such as leiomyosarcoma of the aorta are extremely rare. This report discusses the exceptional and concomitant association of Takayasu arteritis and aortic leiomyosarcoma in a 55-year-old male. The patient suffered from systemic signs and symptoms related to arteritis together with claudication of left upper limb due to left artery subclavian stenosis. After instrumental evaluation, an infiltrating neoplasm at the level of abdominal aortic wall was detected and the patient underwent en bloc excision of the mass together with abdominal aorta and subsequent aortoaortic by pass reconstruction. Histologic findings showed an arterial leiomyosarcoma combined with elements of arterial inflammation. Patients completed therapeutic scheme with chemotherapy (doxorubicin and isosfamide) and radiotherapy for the cancer condition, as well as medical treatment (prednisone and adalimumab) for Takayasu arteritis. After 12 months, the patient showed no cancer recurrence and complete normalization of inflammatory indexes and symptoms of Takayasu arteritis.

Resection of Carotid Body Tumors reduces arterial blood pressure. An underestimated neuroendocrine syndrome.

INTRODUCTION: Carotid Body Tumors (CBTs) are Paragangliomas (PGLs) located in the head and neck region which usually do not cause overt neuroendocrine symptoms and hypertension. Matrix Metalloproteinases (MMPs) have shown a strong correlation between CBTs and their clinical behavior. Aim of this study is to analyze the relationship between changes in arterial blood pressure and metalloproteinases levels after surgical resection of CBTs. METHODS: We performed a multicenter clinical study on 17 patients with benign and malignant CBTs (5 males; 12 females). Tumors were completely resected and biopsies, obtained at the time of surgery, were lysed for Western blot analysis to determine MMPs levels in tissues. An enzyme-linked immune sorbent assay (ELISA) kit was used to determine the concentration of MMPs in plasma fluid. Blood pressure values were measured at admission and at 10 days after surgery. RESULTS: At the time of the admission, blood pressure values were higher in patients with CBTs respect to control patients; moreover in patients with malignant CBTs blood pressure values were higher (P < 0.01) respect to patients with benign CBTs. 10 days after the surgery, we documented a significant decrease (P < 0.01) in blood pressure values and in MMPs levels in all patients with CBTs. CONCLUSION: These results suggest that, despite the CTBs are considered non-functional tumors, an "underestimated" neuroendocrine activity on arterial blood pressure may be detected.

Carotid and vagal body paragangliomas.

Between 1972 and 2012, 25 patients presenting 32 paragangliomas of the neck were observed. Tumor locations included the carotid body (CBTs) in 21 patients and the vagus nerve in 4. Four patients had bilateral CBT and one a bilateral vagal tumor; a metachronous bilateral jugulare paraganglioma was diagnosed in one patient with bilateral CBT Shamblin type III. Five patients presented CBTs type II and three type III. Preoperative embolization was performed in 5 CBTs, with no significant difference in blood loss. Twenty-nine paragangliomas were resected (with three internal carotid artery resection): there were no cerebrovascular accident or perioperative death. Nine patients (36%) had cranial nerve palsy prior to surgery and a postoperative nerve dysfunction occurred in four other tumors (16%). Persistent nerve deficits occurred in 3 patients (12%). No evidence of malignancy was shown, intraoperatively or during a postoperative follow-up period (9 months to 18 years; mean: 8 years).