S Michelini

Bio: S Michelini is an academic researcher from University of Genoa. The author has contributed to research in topics: Medicine & Lymphedema. The author has an hindex of 5, co-authored 10 publications receiving 288 citations.

Diagnosis and treatment of primary lymphedema. Consensus document of the International Union of Phlebology (IUP)-2009

Abstract: Primary lymphedema can be managed safely as one of the chronic lymphedemas by a proper combination of DLT with compression therapy. Treatment in the maintenance phase should include compression garments, self management including the compression therapy, self massage and meticulous personal hygiene and skin care in addition to lymph-transport promoting excercises. The management of primary lymphedema can be further improved with proper addition of surgical therapy either reconstructive or ablative. These two surgical therapies can be effective only when fully integrated with MLD-based DLT postoperatively. Compliance with a long-term commitment of DLT postoperatively is the most critical factor determining the success of any new treatment strategy with either reconstructive or palliative surgery. The future of management of primary lymphedema caused by truncular lymphatic malformation has never been brighter with the new prospect of gene-oriented management.

Diagnosis and treatment of primary lymphedema. Consensus document of the International Union of Phlebology (IUP)-2013.

Abstract: Primary lymphedema can be managed effectively as a form of chronic lymphedema by a sequenced and targeted treatment and management program based around a combination of Decongestive Lymphatic Therapy (DLT) with compression therapy, when the latter is desired as an adjunct to DLT. Treatment in the maintenance phase should include compression garments, self-management, including self-massage, meticulous personal hygiene and skin care, in addition to lymphtransport-promoting excercises and activities, and, if desired, pneumatic compression therapy applied in the home. When conservative treatment fails, or gives sub-optimal outcomes, the management of primary lymphedema can be improved, where appropriate, with the proper addition of surgical interventions, either reconstructive or ablative. These two surgical therapies can be more effective when fully integrated with manual lymphatic drainage (MLD)-based DLT postoperatively. Compliance with a long-term commitment to MLD/DLT and particularly compression postoperatively is a critical factor in determining the success of any new treatment strategy involving either reconstructive or palliative surgery. The future of management of primary lymphedema has never been brighter with the new prospect of gene-and perhaps stem-cell oriented management.

IUA-ISVI consensus for diagnosis guideline of chronic lymphedema of the limbs.

Abstract: The current document is intended to define a consensus on the diagnostic guidelines for patients with lymphedema, based upon literature­based evidence, both clinical and investigative. General diagnostic guidelines include systemic evaluation; assessment of venous function; duplex ultrasonography; and lymphoscintigraphy. Proper diagnosis should allow appropriate clinical and laboratory staging of the disease for the assessment of progression of the condition and its response to treatment. Diagnosis should include an assessment of the infections in the early and latent stages. Lymphedema is assessed by the stage of disease (0­III) and WHO guidelines for International Classification of Functioning, Disability and Health and Quality of Life issues can be used as a reference for the impact of this complex condition on social, emotional, and physical function. It is the authors’ intent that this document stimulate further inquiry and discussion regarding all aspects of lymphedema diagnosis.

The CEAP-L classification for lymphedemas of the limbs: the Italian experience.

Abstract: Aim A method to classificate lymphedema has been needed to gather all the important information on the clinical evolution of the disease using a common language and an easy clinical applicability. Methods The proposal for a new classification of the limb lymphedema was inspired by the C.E.A.P. classification for chronic venous insufficiency of the lower limb. The classification adopts the acronym C.E.A.P. by adding the letter L to underline the aspect ''lymphedema'' and is based on clinical data such as extension of lymphedema, presence of lymphangitis, leg ulcers and loss of functionality of the limb and instrumental criteria that permit to confirm and precise diagnosis. The Clinical classification is based on the most objective sign in these patients, the edema which is subdivided into 5 classes depending on the clinical manifestations. The etiological aspect considers 2 types of alterations of the lymphatic system: congenital and acquired. The anatomic is aimed to locate the anatomical structures involved. Pathophysiological conditions are gathered into 5 groups: agenesia or hypoplasia, hyperplasia, reflux, overload, obstruction. Results The classification has already been appraised after 4 years of activity at the unit of Vascular and Endovascular Surgery of Ferrara, at the S. Giovanni Battista Hospital in Rome, at the Umberto I Ancona Hospital and at the S. Giovanni-Addolorata Hospital in Rome. Conclusions The proposal for a new classification of lymphedema C.E.A.P. L was developed in order to categorize patients with definite and objective marks, creating clinical reports with a common vocabulary, clear to all clinicians, permitting to stage the disease, evaluate treatment and finally obtain epidemiological and statistical data.

A Multi-Gene Panel to Identify Lipedema-Predisposing Genetic Variants by a Next-Generation Sequencing Strategy

Abstract: Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis

Abstract: Objective: Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by venous congestion, a condition termed chronic cerebrospinal venous insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage. Methods: We performed an extended extra- and transcranial color-coded sonography study including analysis of extracranial venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during Valsalva maneuver (VM), and CCSVI criteria. Fifty-six MS patients and 20 controls were studied. Results: Except for 1 patient, blood flow direction in the IJVs and VVs was normal in all subjects. In none of the subjects was IJV stenosis detected. IJV and VV BVF in both groups was equal in the supine body position. The decrease of total jugular BVF on turning into the upright position was less pronounced in patients (173 6 235 vs 362 6 150ml/min, p 1 criterion for CCSVI. Interpretation: Our results challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation. ANN NEUROL 2010;68:173–183

Indications for medical compression stockings in venous and lymphatic disorders: An evidence-based consensus statement:

Abstract: Objective Medical compression stockings are a standard, non-invasive treatment option for all venous and lymphatic diseases. The aim of this consensus document is to provide up-to-date recommendations and evidence grading on the indications for treatment, based on evidence accumulated during the past decade, under the auspices of the International Compression Club. Methods A systematic literature review was conducted and, using PRISMA guidelines, 51 relevant publications were selected for an evidence-based analysis of an initial 2407 unrefined results. Key search terms included: 'acute', CEAP', 'chronic', 'compression stockings', 'compression therapy', 'lymph', 'lymphatic disease', 'vein' and 'venous disease'. Evidence extracted from the publications was graded initially by the panel members individually and then refined at the consensus meeting. Results Based on the current evidence, 25 recommendations for chronic and acute venous disorders were made. Of these, 24 recommendations were graded as: Grade 1A (n = 4), 1B (n = 13), 1C (n = 2), 2B (n = 4) and 2C (n = 1). The panel members found moderately robust evidence for medical compression stockings in patients with venous symptoms and prevention and treatment of venous oedema. Robust evidence was found for prevention and treatment of venous leg ulcers. Recommendations for stocking-use after great saphenous vein interventions were limited to the first post-interventional week. No randomised clinical trials are available that document a prophylactic effect of medical compression stockings on the progression of chronic venous disease (CVD). In acute deep vein thrombosis, immediate compression is recommended to reduce pain and swelling. Despite conflicting results from a recent study to prevent post-thrombotic syndrome, medical compression stockings are still recommended. In thromboprophylaxis, the role of stockings in addition to anticoagulation is limited. For the maintenance phase of lymphoedema management, compression stockings are the most important intervention. Conclusion The beneficial value of applying compression stockings in the treatment of venous and lymphatic disease is supported by this document, with 19/25 recommendations rated as Grade 1 evidence. For recommendations rated with Grade 2 level of evidence, further studies are needed.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management.

Abstract: Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Lymphoedema: estimating the size of the problem

Abstract: Lymphoedema is a problem frequently encountered by professionals working in palliative care. This article reviews the evidence on the magnitude of the problem of lymphoedema in the general population and provides evidence on specific high risk groups within it. Prevalence is a good indicator of the burden of disease for chronic problems such as lymphoedema, as it indicates the numbers of patients who require care. Incidence is indicative of changes in the causes of lymphoedema and the success of any prevention programmes. Both are important means of assessing the current level of need and the potential for the changing needs in managing this condition. Problems exist in all studies in relation to precise definitions of lymphoedema, inconsistent measures to assess differential diagnosis and poorly defined populations. While there is some evidence of high rates in relation to breast cancer therapy, the total burden of lymphoedema in the general population is largely unknown.

Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery.

Abstract: We analyzed clinicopathologic and imaging features of chronic peripheral lymphedema to identify imaging findings indicative of its exact etiopathogenesis and to establish the optimal treatment strategy. One of the main problems of microsurgery for lymphedema is the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic studies and surgical outcome have not been adequately documented. Over the past 25 years, 676 patients with peripheral lymphedema have been treated with microsurgical lymphatic-venous anastomoses. Of these patients, 447 (66%) were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Objectively, volume changes showed a significant improvement in 561 patients (83%), with an average reduction of 67% of the excess volume. Of the 447 patients followed, 380 (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was an 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed early, during the first stages of lymphedema.