Addition of Intermittent Pneumatic Compression to Conventional Treatment Improves Volume Reduction Before Lymphatic Surgery for Lower Limb Lymphedema: A Pilot Study.

This study assesses the impact of an advanced intermittent pneumatic compression device (IPC - Lympha Press® Optimal Plus) when added to Complete Decongestive Therapy (CDT) compared to CDT alone on volume reduction of limbs with lymphedema. The goal is to maximally reduce edema in preparation for microsurgery. Fifty subjects scheduled for Multiple Lymphatic-Venous Anastomosis (MLVA) were randomly (sequentially) assigned to experimental or control group: 25 (21 females and 4 males) in the experimental IPC group and 25 (20 females and 5 males) in the control group. The two groups were similar in age, sex distribution, and type of lymphedema. Results indicate the IPC group reported greater volume loss than the control group (p= 0.00137) comparing final vs. initial limb volume. The average percentage edema volume loss achieved with added IPC was two times greater (11.7%) than in the control group (5.0%). When differences in treatment duration were accounted for, the IPC group achieved consistently greater proportional volume loss (12.83% vs 6.30%) than conservative therapy alone. In our pilot study, IPC added to CDT resulted in greater proportional volume loss and provides better preparation for MLVA surgery.

Lymphovenous anastomosis for the treatment of lymphedema: A systematic review of the literature and meta-analysis.

Lymphovenous anastomosis (LVA) has been described as an effective treatment for early stages of lymphedema (LE). The aim of this study was to deepen the evaluation of the effectiveness of LVA by performing a metaanalysis to provide information about its utility in specific anatomical sites, clinical stages, duration of lymphedema, and surgical technique. A systematic literature search using PubMed/Medline, Google Scholar, and Cochrane Database was performed in November 2019. Only original studies in which exclusively LVA was performed for primary and/or secondary lymphedema in humans were eligible for data extraction. A meta-analysis was performed on articles with a well-defined endpoint and a subgroup analysis was conducted in relation to surgical technique, duration of lymphedema, stage of pathology. Forty-eight studies, including 6 clinical trials and 42 lowrisk bias observational studies were included in our meta-analysis. 1,281 subjects were included and the majority of articles reported a pre-post analysis. Lymphaticovenular anastomosis appears to result effectively in treatment of lymphedema with an odds ratio of 0.07 (CI: 0.04, 0.13, p<0.001). All subgroup metaanalyses were statistically significant for LVAs specifically with regard to anatomical site, clinical stage, duration of LE, or type of microsurgical procedure (p<0.05). Our meta-analysis confirmed the efficacy of LVAs for the treatment of lymphedema, even when subgroup analysis was performed for clinical stage, duration of pathology, anatomical site of lymphedema, or type of microsurgical procedure. Further prospective trials with a common clearly defined outcome measure are warranted for an unbiased evaluation.

Multiple lymphatic-venous anastomoses (MLVA) for microsurgical drainage of primary peno-scrotal lymphedema: A case report.

Single site Multiple Lymphatic-Venous Anastomoses (MLVA) provides optimal functional and cosmetic results with low complication rates in treatment of lower limb lymphedema. However, no evidence exists in literature concerning the use of this technique in treatment of peno-scrotal lymphedema. We report a case of a 44-year-old male patient who developed secondary peno-scrotal lymphedema with severe lymphorrhea, following a laser treatment for scrotal pustolosis, leading to recurrent infections and finally an established peno-scrotal lymphedema. Utilizing MLVA, a complete remission of scrotal lymphedema was achieved with significant volume reduction of the penile lymphedema. The post-operative course was uneventful with clear improvement in lymphatic flow demonstrable on lymphoscintigraphy (6 months) and no recurrence of scrotal lymphedema at 2 years follow-up. This article reports very promising results of a novel application of MLVA in the treatment of genital lymphedema and suggests that MLVA provides the possibility to shunt both superficial and deep lymphatics to improve the lymphatic drainage from the peno-scrotal area using a single surgical site.

Procedural Recommendations for Lymphoscintigraphy in the Diagnosis of Peripheral Lymphedema: the Genoa Protocol.

INTRODUCTION: Lymphoscintigraphy is the gold standard for imaging in the diagnosis of peripheral lymphedema. However, there are no clear guidelines to standardize usage across centers, and as such, large variability exists. The aim of this perspectives paper is to draw upon the knowledge and extensive experience of lymphoscintigraphy here in Genoa, Italy, from our center of excellence in the assessment and treatment of lymphatic disorders for over 30 years to provide general guidelines for nuclear medicine specialists. METHOD: The authors describe the technical characteristics of lymphoscintigraphy in patients with limb swelling. Radioactive tracers, dosage, administration sites, and the rationale for a two-compartment protocol with the inclusion of subfascial lymphatic vessels are all given in detail. RESULTS: Examples of lymphoscintigraphic investigations with various subgroups of patients are discussed. The concept of a transport index (TI) for semi-quantitative analysis of normal/pathological lymphatic flow is introduced. Different concepts of injection techniques are outlined. DISCUSSION: It is past time that lymphoscintigraphy in the diagnosis of lymphatic disorders becomes standardized. This represents our first attempt to outline a clear protocol and delineate the relevant points for lymphoscintigraphy in this patient population.

Inclusion of targeted skin products in the pre-surgical treatment regimen of peripheral lymphedema & lipedema.

Advanced lymphedema is associated with a number of adverse skin changes including color, thickening of the epidermis, dryness, and hyperkeratosis. These changes are related to prolonged lymph stasis and contribute to an increased risk of infection. Similarly, lipedema is associated with skin thickening and appearance of nodular adipose deposition. Skin care is essential in both conditions. We examined whether inclusion of targeted skin products for 2 weeks to an established pre-surgical conservative treatment program was associated with beneficial effects on the skin condition in 150 patients with lymphedema and lipedema. Patients were randomly assigned to control or one of two treatment groups. All three groups (and for both lymphedema and lipedema) demonstrated a significant reduction in softness. Dimpling/ redness was significantly reduced in the targeted skin product groups for both patients with lymphedema or lipedema. Only patients with lipedema demonstrated a significant reduction in dryness/ hyperkeratosis following targeted skin product treatment. This study demonstrates that short-term use of targeted skin products in both patients with lymphedema and lipedema can be of benefit and further studies are needed to replicate these results and explore possible mechanisms.

Decreasing and preventing lymphatic-injury-related complications in patients undergoing venous surgery: A new diagnostic and therapeutic protocol.

Lymphatic complications following great and small saphenous vein surgery show a varying and non-negligible incidence in the literature. We undertook this study to investigate a new protocol to reduce lymphatic injuries in patients undergoing venous surgery. Eighty-six patients with lower limb venous insufficiency and varices were treated. Lymphoscintigraphy was performed preoperatively in 65 of them and postoperatively in 19. Blue dye was used in all patients and blue lymph nodes and lymphatics were identified intra-operatively and preserved or used to perform multiple lymphatic-venous anastomoses (MLVA). Patients were followed up fora period varying from 3 months to 6 years. Sixty-six patients were treated by greater saphenectomy and varicectomy, 12 patients had crossectomy and varicectomy, 4 patients underwent greater saphenectomy and varicectomy associated with MLVA, and 4 patients were treated by small saphenous vein stripping and varicectomy. No lymphatic complications occurred in any of the patients. A decrease of over 75% of excess volume was observed in 4 patients treated by MLVA. Lymphoscintigraphy showed normalization in the Transport Index in 4 patients treated with MLVA. Our results demonstrate that accurate diagnostic investigation and proper surgical technique is of paramount importance in the effort to avoid lymphatic complications during venous surgery.

In Memoriam Prof. Prof. h.c. Dr. med. Michael Földi, January 10, 1920 - October 20, 2018 "Father of Lymphology".

In Memoriam: With deep sadness the world of Lymphology learned of the death of Prof. Prof. h.c. Dr. med. Michael Földi, a ground breaking pioneer of modern Lymphology. Words alone will never fully describe or capture the breadth and depth of Michael's contribution to our lymphatic knowledge and the legacy he has left for us all.

Chyloperitoneum: Diagnostic and Therapeutic Options.

Chyloperitoneum is not rare and is often associated with other chylous disorders particularly in more complex clinical conditions. An accurate diagnostic study is indispensable to plan the correct therapeutic approach, and we examined the long-term outcomes of our experience in the management of primary and secondary chyloperitoneum in fifty-eight patients (50 adults and 8 children; 34 primary and 24 secondary forms). Diagnostic assessment consisted of aracentesis, whole body lymphoscintigraphy, lymphangio-MR, and lymphangio-CT (LAG-CT). The management of chyloperitoneum consisted initially of non-operative procedures (MCT diet, TPN, octreotide). Surgical treatment was performed in patients not responsive to conservative methods and involved different options using surgical and microsurgical approaches. Microsurgical techniques included chylousvenous shunts connecting chyliferous vessels and mesenteric veins. Fibrin glue or platelet gel injection at the site of the chylous leakage was also used to treat one case of refractory secondary chyloperitoneum. Patients were followed clinically and instrumentally (echography and labs tests) for 6 months to over 5 years. We found that LAG-CT was the primary diagnostic modality to provide precise topographic information concerning the site, cause, and extension of chylous pathology, all of which allowed proper planning of therapeutic procedures. Thirty-four patients did not have a relapse of the chyloperitoneum and 22 patients had a persistence of a small quanitity of ascites with no protein imbalance. We observed early relapse of chylous ascites in 2 cases that required a peritoneal-jugular shunt leading to good outcomes. An accurate diagnostic study (above all LAG-CT) and a microsurgical approach proved to represent an effective management of chyloperitoneum refractory to non-operative treatment.

Chylothorax as Rare Manifestation of Pleural Involvement in Waldenström Macroglobulinemia: Mechanisms and Management.

Here we report the clinical, pathological, and immunological features of a rare case of Waldenström macroglobulinemia (WM) with pleural infiltrations. An atypical chylothorax, successfully treated by videothoracoscopy, represented the main clinical feature of this case of low-grade lymphoplasmacytic lymphoma. Pleuropulmonary manifestations are rare (from 0 to 5% of cases) in WM, with chylothorax observed in just seven patients worldwide. In addition to describing this uncommon clinical presentation, we investigate hypothetical pathogenetic mechanisms causing chylothorax and through an up-todate review of available literature furnish helpful suggestions for diagnosis and management of chylothorax in WM patients.

OPTIMIZING THE STAGING OF MELANOMA PATIENTS FOR THEIR BEST SURGICAL MANAGEMENT.

Interval nodes (IN) are defined as lymph nodes that lie along the course of lymphatic collecting vessels between a primary tumor site and a draining node field. Sometimes INs contain metastases and a consensus on their surgical management is needed. Therefore, to optimize the surgical management of melanoma patients with metastatic lymphatic involvement, especially when the sentinel lymph node biopsy identifies an unusual drainage field, we identified patients treated at the Department of Plastic and Reconstruction Surgery of Bari between July 1994 and December 2012 identified with a primary-cutaneous melanoma who underwent lymphoscintigraphy and subsequent positive-IN the lymphadenectomy to evaluate the impact of this procedure on overall survival and disease-free-period. 51 patients presented INs, and lymphadenectomy (LA) of the subsequent lymphatic field was performed in 13 subjects with positive-IN. In 4 cases additional lymphatic metastases were detected in the usual basin beyond the IN+. Recurrence-free period and survival rate at 5 years were higher in patients with positive-IN who underwent LA than in subjects who underwent LA due to positive lymph nodes in the usual field. Immediate lymphadenectomy of the subsequent lymphatic field in patients with positive-INs may afford patients earlier stage treatment of their disease and improved prognosis.

INTERMITTENT NEGATIVE PRESSURE THERAPY IN THE COMBINED TREATMENT OF PERIPHERAL LYMPHEDEMA.

Intermittent negative pressure devices were initially developed by NASA to enhance blood perfusion and combat a reduction in orthostatic tolerance. Investigational studies have demonstrated that the pressure differential produces changes in the blood and cardiac systems and also documented changes in weight and cellulite in obese patients. Although the mechanisms are not known, previous investigation has also reported changes in lymphedematous limbs. These initial results suggested to us that the inclusion of intermittent negative pressure into a lymphedema treatment protocol would be beneficial. We subsequently undertook a study of 50 patients with lymphedema adding intermittent negative pressure to our CLyFT protocol and compared them to the CLyFT protocol without intermittent negative pressure. We found a significant difference between the groups with an additional 7% reduction in lymphedema volume (p = 0.008). Our study results indicate that the inclusion of intermittent negative pressure therapy into the CLyFT protocol was beneficial and further incorporation into other protocols should be investigated.

Dermatological consultations in an observation unit of an emergency department in Italy.

BACKGROUND: Dermatological emergencies exist and should not be underestimated. On the other hand, many accesses to the emergency department (ED) of patients with dermatological conditions are unjustified. OBJECTIVE: Our main objective is to describe dermatological conditions seen in an ED observation unit (EDOU). Secondly, our aim is to identify alarm symptoms and signs of 'true emergencies'. METHODS: We conducted a prospective study, including dermatological patients admitted to EDOU of the University Hospital of San Martino, Genoa, Italy, in 3 years. RESULTS: Overall 372 patients were studied. The most common condition seen was infection (41.67%) (mainly bacterial), followed by atypical exanthem (13.98%) and vasculitis (11.29%). The highest rate of cases peaked in May (13%); infectious diseases showed two peaks (spring and autumn). CONCLUSION: Given constraints involved in health care today, it is crucial to understand which dermatological presentations are 'true emergencies'. In such a scenario knowing the epidemiology of dermatological emergencies and the alarming skin signs and symptoms might be useful.

Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.

Chylopericardium: a case report demonstrating utility of lymphography combined with 3D computed tomography for corrective surgical treatment using VATS.

We present a case of a 58 year-old woman with primary chylopericardium associated with chylothorax. Chylopericardium is a condition in which chylous fluid containing a high concentration of triglycerides accumulates in the pericardial cavity, and it can form for many different reasons. 3D computed tomography with lymphography precisely depicted the specific location of the lymphatic leak in this patient, which was successfully repaired using targeted video assisted thoracic surgery (VATS).

Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role of the lymphatic system.

Pleural fluid effusion particularly chylothorax is a relatively rare occurrence in the newborn, but when it occurs it is often life-threatening. In this article, we describe and illustrate the morphologic features of the visceral and parietal pleura including pleural lymphatics and the physiology and pathophysiology of pleural fluid balance. The role and function of the lymphatic system in controlling the volume and composition of pleural liquid are detailed and a conceptual scheme presented. Finally, the crucial role of inadequate lymphatic drainage (either functional overload from an imbalance in Starling forces or mechanical insufficiency from lymphatic dysplasia) is emphasized.

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

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.

Surgical prevention and treatment of lymphedema after lymph node dissection in patients with cutaneous melanoma.

Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.

Immunodeficiency due to chylous dysplasia: diagnostic and therapeutic considerations.

Among primary immunodeficiencies, common variable immunodeficiency (CVID) is defined by an impaired production of immunoglobulins characterized by low levels of plasma immunoglobulins and an altered antibody response. The case reported here was initially interpreted as a CVID. A 20 year old male suffered from diarrhea, weight loss, and malnutrition. Accurate diagnostic assessment uncovered a protein-losing enteropathy. Conventional oil contrast lymphangiography accurately documented the underlying problem and established the appropriate therapeutic approach. The operation consisted of multiple antigravitational ligatures of dilated and incompetent chylous vessels and chylous vessel-mesenteric vein microanastomoses. Serum albumin and leukocyte counts normalized by 1 week after operation and remained stable with time. There were no more episodes of diarrhea, and the patient regained weight. Accurate diagnostic assessment and particularly lymphangiography may be necessary to properly define difficult cases of immunodeficiency due to intestinal protein loss and to plan a corrective therapeutic functional approach.