Marzanna T. Zaleska

The Charles procedure (CP) is a potentially devastating treatment; however, in cases of an end stage of untreated or improperly treated lymphedema, it is the ultimate surgical therapy. As a life‐saving solution, it quickly relieves patients with giant, hypertrophic extremities, mostly in ambulation and hygiene maintenance. Nevertheless, long‐term results may disappoint both doctors and patients, who struggle with social stigma, the need for lifelong compression, massive lymphoedema in the distal parts of the feet, badly fitting shoes, excessive skin fibrosis, severe keratinization of skin‐grafted surfaces, periodic lymphorrhea from the resected areas, or acute and chronic inflammation. For these reasons, patients may seek further surgical help, even many years after treatment. This article describes findings in fluorescent lymphography with indocyanine green (ICG‐L) in four patients (49, 56, 56 years old females and 35 years old males) after CP and outcomes of treatment with lymphaticovenous anastomosis (LVA). In all patients, nonresected areas of the dorsum of the feet showed massive lymphedema stage II to III with dermal backflow (DB). In two patients, resected and skin‐grafted areas showed deep subfascial lymphatics with lazy flow and no DB. In the remaining two cases, resected areas showed massive DB. Patients were reluctant to undergo further extensive surgical treatment with lymph node transfers due to the trauma experienced after CP. Since they still struggle with residual lower extremity lymphedema in unresected areas of the lower limbs, we performed minimally invasive, physiologic LVA surgeries in their feet, and in one patient in proximal thighs. In all cases, the postoperative course was uneventful. The treatment brought relief, reducing the circumference of the feet by ~2 cm, and allowed the return to previously used shoes in a follow‐up of 18–36 months. This is the first report of ICG‐L findings in CP patients, who benefit from minimal invasive LVA surgery. This information might help improve the life quality of patients after CP.

Background: Lipedema of lower limbs is characterized by bilateral accumulations of excess adipose tissue starting from the ankle to the hips and buttocks. The studies with lymphoscintigraphy (LSC) and magnetic resonance (MR) lymphography show altered transport index and enlarged lymphatic vessels (LVs). Our studies aimed to investigate the superficial lymph flow, water accumulation, skin and subcutaneous tissue elasticity, and the possibility of using this information to diagnose lipedema. Methods and Results: Fifty patients with lipedema and 50 control subjects (women) were included. The Indocyanine Green (ICG) lymphography, LSC, skin water measurement, skin durometry, and deep tissue tonometry were done in all participants. ICG lymphography revealed: (1) Slower lymph flow in lipedema patients; after 3 minutes of feet movement in a horizontal position, the ICG-dyed lymph reached the upper calf level in 8% of lipedema patients compared with 56% in the control group ( p ˂ 0.0001). (2) More than three LVs were noticed more often in lipedema patients. (3) The higher number of abnormal LV images at all limb levels and during each observation stage with a statistically significant number of foggy and dilated. (4) Statistically significant higher fluorescent intensity in all limb levels. Skin water concentration was higher in the feet in lipedema ( p = 0.000189). Conclusion: Our studies have shown the differences in superficial lymph flow and water concentration between lipedema and normal limbs. Data proove the usefulness of ICG lymphography, skin water concentration and skin and subcutaneous tissue elasticity measurements in diagnosing lipedema.

Background: The lymphedema-affected limbs are predisposed to acute and, subsequently, chronic dermato-lymphangio-adenitis (DLA) episodes in around 40%–50% of cases, irrespective of what the primary etiological factor is for the development of this condition. DLA is of bacterial etiology, and it needs antibiotic control and prevention of recurrence. Aim: To follow the effects of years-long continuous no-break administration of benzathine penicillin on the recurrence of acute DLA episodes. Methods and Results: Two hundred thirty-one patients were affected with lymphedema of lower and upper limbs. The mean duration of lymphedema was 10.2 ± 7.3 (range 2–30) years, and the number of DLA attacks/patient was 3.3 ± 3.2 (range 1–10). The total number of DLA episodes was 805. Benzathine penicillin injections 1,200,000 units were given i.m. at 14–21 days intervals (mean 18 ± 9 days) with short accidental breaks only. The period of therapy was 39.2 ± 38.7 (median 32) months. Recurrence occurred in 23 out of 231 (10%) (p < 0.01). There were 42 DLA incidents compared with 805 before introduction of therapy (5.2%) patients (hazard ratio 0.05, 95% confidence interval 0.034–0.079) (p < 0.01). Among patients with recurrence, there was a decrease of DLA episodes from 6.2% ± 3.6% to 1.7% ± 1.0%/patient. There were no differences in effectiveness of penicillin prophylaxis between etiological groups, depending on stages of lymphedema. Conclusions: Long-term years-long benzathine penicillin prophylaxis is extremely effective in prevention of DLA recurrence. It can be applied for years with no breaks, without clinical side-effects, and raising resistance to antibiotics. Microbial colonization and evoked inflammatory reaction of hosts should be controlled from the first symptoms of lymph stasis, irrespective of the etiology of lymphedema.

Background: Delayed onset muscle soreness (DOMS) in runners is classified as a leg muscle strain injury and presents with tenderness or stiffness to palpation and movement limitation. Most attention is directed at muscles but not at the mass of other limb soft tissues, including their lymphatic vasculature, although they undergo mechanical stress and bruises, edema, nail destruction, and pains contributing to symptoms. Methods: The study was done on lower limbs of long-distance runners suffering from DOMS complaints. There were 16 runners, 11 males and 5 females, age 22–28, practicing long-distance running over the last 5 years, with body mass index (BMI) 23 ± 4. Inclusion criteria: three to five marathon runs per year and daily 3–5 km slow runs. Last long distance run 3 to 7 days before the investigation. Controls were six subjects initiating running, of the same age group and BMI. Testing of blood and lymph flow was done before and after standard ergometer 300 W 30 minutes cycling. The measurement methods were leg and big toe venous plethysmography, big toe capillary Doppler, tonometry of skin and deep tissues, lymphoscintigraphy, and indocyanine green (ICG) fluorescent lymphography. Results: (a) Strain gauge plethysmography of the calf and big toe revealed a two- to three-times higher venous capacity in runners than in controls, (b) the increased toe venous capacity was confirmed by point Doppler recordings showing two- to three-times higher blood capillary flow compared to controls, (c) lymphoscintigraphy revealed retention of tracer in feet, dilated superficial and deep lymphatics, and enlarged popliteal and inguinal lymph nodes, and (d) ICG lymphograms showed confluents of accumulated fluid in foot and calf subcutaneous tissue with fluorescence level reaching 40%–50% compared to 20% in controls. Conclusion: Our results show that, 3–5 days after run, not only muscles but also skin and subcutaneous tissue reveal major tissue fluid accumulation, an overload bringing about functional lymphatic transport insufficiency. This may be an additional factor responsible for DOMS symptoms.

Why do the saphenous vein varices arise? According to our concept this is a process of slow deconstruction of the vein wall by inflammation caused by microbes penetrating plantar skin, colonizing deep tissues, entering veins and sticking to valves, as well as, transported to lymphatics, bringing about damage to their wall and evoking immune response in the inguinal lymph nodes. Venous stasis caused by a variety of hemodynamic factors remains secondary to the primary damage of the vein wall. With respect to ulcer, irrespective of the predisposing factors as venous stasis, colonization of the denuded calf surfaces takes place by bacteria drained from foot skin and also those floating down to calf from the perineum. This set of microbes is responsible for progression of ulcer or its delayed healing. In this study, the numerical phenotypes of varicose veins and ulcer granulation tissue bacteria were presented. The dominant strains in the vein walls were Staph. epidermidis and aureus with Enterococci and Pseudomonas frequent in ulcers. High percentage of Staphylococci both in vein walls and ulcer sensitive to antibiotics may suggest that they originated from the microbiome inhabiting leg tissues prior to the development of varices and ulcer.

The commonly used modalities for therapy of limb lymphedema are manual lymphatic drainage, manual devices moving edema fluid and intermittent pneumatic compression (IPC). What seems to be necessary for validation of the effect of the compression procedure is imaging of the mobilized moving edema fluid. Picture of edema fluid flow would allow the therapist to use force adjusted to the tissue volume and stiffness differing in various limb regions as well as identify sites of abundant accumulation of fluid requiring more compression. The purpose of the present study was to visualize tissue edema fluid flow during manual drainage, Linforoll massage, IPC and bandaging. To obtain data how high compression pressures should be used to mobilize indocyanine green (ICG)‐stained fluid, concomitantly tissue fluid pressure measurements were performed. The following observations were obtained: (1) the possibility of real‐time observation of edema fluid movement using various compression modalities, (2) the threshold pressures necessary to move edema fluid to be over 80 mm Hg in the compression device and over 40 mm Hg in the tissue fluid and (3) inefficacy of compression in some cases despite applying high compression force. These observations point to the need of ICG lymphangiography before compression therapy in each patient. The images observed during the compression procedure give an insight into the distribution of edema fluid, sites of its accumulation and efficacy of applied external force on fluid mobilization.

The human lymphatic system morphology and function still remain largely unknown to clinicians and biologists. How does the lymphatic vascular system look like in comparison to the blood transport system, how does lymph flow, where does capillary filtrate accumulate in cases with lymphatic obstruction caused by inflammation, trauma, and cancer therapy, remain as basic questions. Visualization of the lymphatic pathways and dynamics of lymph flow, and in cases of obstruction, the localization of the capillary filtrate/edema fluid accumulation becomes indispensable. The contemporary methods only partly meet these requirements. Since the early 1950s of the 20th century only few specific clinical methods of imaging of limb lymphatics are being used in human clinic. Each of the applied modalities provides different images due to different physical chemistry and distribution of tracer, methods used for its detection in tissues, their sensitivity and specificity and clinical type of lymph vessel pathology. Here, the advantages and disadvantages of the most commonly used 3 methods of imaging: the iodinated oil X‐ray, isotopic, and fluorescent lympangiographies are presented. The study is based on retrospective and recent collections of lymphangiograms from large cohorts of patients. Imaging of lymph nodes has not been included as it is requiring different interpretation compared with vessels. Composite evaluation of X‐ray, isotopic, and fluorescent lymphographic images or, as it is practiced now the isotope and indocyanine green near infrared lymphographies, provide most clinically important information. Special attention was directed at methods enabling early diagnosis of imminent lymphedema especially in cases with cancer therapy‐related lymphedema. Groups of typical images obtained with the 3 methods are presented.

Background: Lymphedema of limbs affects a large mass of tissues. Pathological changes develop in skin and subcutaneous tissue. Bacterial retention in edema fluid is followed by chronic inflammatory reaction. The question arises whether the chronic processes affecting a large mass of limb tissues are reflected in the serum by appearance of specific proteins accumulating and subsequently absorbed from the lymphedematous tissues Aim: To measure the concentration of serum proteins (1) participating in cellular disintegration such as caspase 1, sFas, high-mobility group box 1 (HMGB1), and serpin, (2) cell growth regulating factors such as cortisol, human growth hormone, keratinocyte growth factor, and insulin-like growth factor (IGF), and (3) angiogenic and growth factors such as angiopoetins 1 and 2, adiponectin, leptin, and transforming growth factor beta. Results: We found (1) increased concentration of serum caspase 1, sFas, serpin, and HMGB1 accounting for cellular destruction, (2) raised levels of cortisol and IGF, confirming active cellular processes, and (3) elevated concentrations of angiopoetin 1, adiponectin, and leptin, indicating proliferation of adipose tissue. Conclusions: Proteins appearing in serum in high concentrations in patients with lymphedema without systemic clinical and biochemical signs of inflammation indicate that multiple processes of destruction and rebuilding proceed in the lymphedematous tissues. Measuring concentration of caspase 1, sFas, serpin, HMGB1 protein, adiponectin, and leptin give insight into these processes. Lymphedema should be considered as tissue process characterized not only by increase in mobile tissue fluid volume but also tissue restructuring. Compression and drainage therapy should be complemented by anti-inflammatory medication.

Infections and inflammation of the lower limb skin, soft tissues, and vessels are more common than in other body regions. The aim was to determine whether cryptic bacteria dwelling in deep tissues are the cause. We performed bacteriologic studies of specimens harvested from arteries of amputated ischemic legs, leg varices, and tissue fluid/lymph and lymphatics in lymphedema. Calf arteries contained isolates in 61% and femoral arteries in 36%, whereas normal cadaveric organ donors' arteries in 11%. Bacterial deoxyribonucleic acid (DNA) was detected in 70%. The majority of isolates belonged to the coagulase-negative staphylococci and Staphylococcus aureus; however, highly pathogenic bacteria were also detected. All were sensitive to all antibiotics except penicillin. Saphenous vein varices contained bacterial cells in 40% and controls 4%; bacterial DNA was found in 69%. The majority of bacteria were S. epidermidis and S. aureus susceptible to all antibiotics except penicillin, Lymph and epifascial lymphatics limb contained bacteria in 60% and 33% samples, respectively and controls in 7%. Most were S. epidermidis susceptible to all antibiotics except penicillin. Cryptic bacteria are present in lower limb tissues and may play a pathologic role in surgical site infections. Proper antibacterial prophylaxis should be considered when planning surgical interventions.