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Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Surgery".

Deadline for manuscript submissions: closed (16 May 2022) | Viewed by 37658

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Prof. Dr. Emanuele Cigna

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Guest Editor

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Interests: plastic surgery; lymphedema; lymphatic surgery; lymph node flap; lymphaticovenular anastomosis; free flaps surgery; perforator flaps; breast reconstruction; melanoma

Dr. Luigi Losco

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Guest Editor

Plastic Surgery Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Via Salvador Allende, 43, Baronissi, 84081 Salerno, Italy
Interests: reconstructive surgery; lymphoedema; lymphatic surgery; lymph node transfer; free-flap surgery; perforator flaps; breast reconstruction; massive weight loss; post bariatric surgery; facial reconstruction
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Dr. Alberto Bolletta

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Guest Editor

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Interests: reconstructive surgery; lymphedema; lymphatic surgery; lymph node flap; lymphaticovenular anastomosis; free flaps surgery; perforator flaps; breast surgery; oncoplastic surgery

Special Issue Information

Dear Colleagues,

Since its first description in 1787 by Professor Mascagni, the tiny but omnipresent lymphatic vessels have occupied a central position in understanding lymphedema. As the pathogenesis of most lymphatic disorders is not yet fully understood, this is an expanding research area; nowadays, in fact, this chronic progressive condition is still underdiagnosed and underestimated.

Primary lymphedema is the result of a development abnormality of the lymphatic system whose onset ranges from childhood to adulthood. In secondary cases, impairment of the lymphatic system can be caused by direct trauma, infection, oncologic surgery or radiotherapy. Lymphedema is not usually life-threatening, but it has a very deleterious effect on quality of life, causing restriction of movement, loss of body image and self-esteem, and an increased risk of infection.

Early diagnosis is relevant in order to set an effective physical therapy protocol and treatment. In the early stages of the pathological process, conservative and nonsurgical treatment can be advised, but in more advanced stages surgery becomes necessary. From conservative therapies to operations performed in severe and refractory cases, treatment of lymphedema remains a challenge.

Given the importance of a rapid and correct diagnosis followed by appropriate treatments, Medicina is launching this Special Issue to offer a broad view on this topic. Authors will have the greatest freedom and the possibility of presenting their scientific results to the international scientific community. We encourage you and your co-workers to submit your articles on this topic. Reviews and original articles dealing with the diagnosis, treatment or rehabilitation of lymphedema are particularly welcome, as are articles and communications reporting evidence and expectations from innovative diagnostic and therapeutic procedures, with a special focus on individualized approaches.

Prof. Dr. Emanuele Cigna
Dr. Luigi Losco
Dr. Alberto Bolletta
Guest Editors

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Keywords

Lymhedema
Ultra-high Frequency Ultrasound
ICG Lymphography
Breast Cancer-Related Lymphedema
Lymphatic Surgery
Lymph Node Transfer
Lymphaticovenular Anastomosis
Conservative Treatment of Lymphedema
Lymphedema Rehabilitation
Health-related Quality of Life
Supermicrosurgery

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 227 KiB

Open AccessEditorial

Editorial for the Special Issue “Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation”

by Alberto Bolletta, Luigi Losco and Emanuele Cigna

Medicina 2024, 60(2), 307; https://doi.org/10.3390/medicina60020307 - 10 Feb 2024

Viewed by 965

Abstract

Lymphedema is a complex clinical condition that appears as a result of the failure of the lymphatic system function, and it is characterized by edema, fibrosis, and adipose deposition [...] Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

Research

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11 pages, 3193 KiB

Open AccessArticle

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis—The Triple Incision Approach

by Anna Amelia Caretto, Gianluigi Stefanizzi, Giorgia Garganese, Simona Maria Fragomeni, Alex Federico, Luca Tagliaferri, Bruno Fionda, Alessandro Cina, Giovanni Scambia and Stefano Gentileschi

Medicina 2022, 58(5), 631; https://doi.org/10.3390/medicina58050631 - 1 May 2022

Cited by 8 | Viewed by 3020

Abstract

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs’ measures were analyzed by Student’s t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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7 pages, 1892 KiB

Open AccessArticle

Distally Prophylactic Lymphaticovenular Anastomoses after Axillary or Inguinal Complete Lymph Node Dissection Followed by Radiotherapy: A Case Series

by Diletta Maria Pierazzi, Sergio Arleo and Gianpaolo Faini

Medicina 2022, 58(2), 207; https://doi.org/10.3390/medicina58020207 - 29 Jan 2022

Cited by 3 | Viewed by 2563

Abstract

Background and Objectives: Lymphedema is an important and underestimated condition, and this progressive chronic disease has serious implications on patients’ quality of life. The main goal of research would be to prevent lymphedema, instead of curing it. Patients receiving radiotherapy after lymph node dissection have a significantly higher risk of developing lymphedema. Through the prophylactic use of microsurgical lymphaticovenular anastomoses in selected patients, we could prevent the development of lymphedema. Materials and Methods: Six patients who underwent prophylactic lymphaticovenular anastomoses in a distal site to the axillary or groin region after axillary or inguinal complete lymph node dissection followed by radiotherapy were analyzed. Patients characteristics, comorbidities, operative details, postoperative complications and follow-up assessments were recorded. Results: Neither early nor late generic surgical complications were reported. We observed no lymphedema development throughout the post-surgical follow-up. In particular, we observed no increase in limb diameter measured at 1, 3, 6 and 12 months postoperatively. Conclusion: In our experience, performing LVA after axillary or groin lymphadenectomy and after adjuvant radiotherapy, and distally to the irradiated area, allows us to ensure the long-term patency of anastomoses in order to obtain the best results in terms of reducing the risk of iatrogenic lymphedema. This preliminary report is encouraging, and the adoption of our approach should be considered in selected patients. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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9 pages, 453 KiB

Open AccessArticle

Prevention of Secondary Lymphedema after Complete Lymph Node Dissection in Melanoma Patients: The Role of Preventive Multiple Lymphatic–Venous Anastomosis in Observational Era

by Eleonora Nacchiero, Michele Maruccia, Fabio Robusto, Rossella Elia, Alessio De Cosmo and Giuseppe Giudice

Medicina 2022, 58(1), 117; https://doi.org/10.3390/medicina58010117 - 13 Jan 2022

Cited by 3 | Viewed by 2109

Abstract

Background and Objectives: Current guidelines have limited the performance of complete lymph node dissection (CLND) for patients with clinically detectable lymphatic metastases. Despite the limitations of this surgical procedure, secondary lymphedema (SL) is an unsolved problem that affects approximately 20% of patients undergoing CLND. Preventive lymphatic–venous micro-anastomoses (PMLVA) has already demonstrated its efficacy in the prevention of SL in melanoma patients with a positive sentinel lymph node biopsy (SLNB), but the efficacy of this procedure is not demonstrated in patients with clinically detectable lymphatic metastases. Materials and Methods: This retrospective cohort study, was performed in two observation periods. Until March 2018, CLND was proposed to all subjects with positive-SLNB andPMLVA was performed in a subgroup of patients with risk factors for SL (Group 1). From April 2018, according to the modification of melanoma guidelines, all patients with detectable metastatic lymph nodes underwent PMLVA during CLND (Group 2). The frequency of lymphedema in subjects undergoing PMLVA was compared with the control group. Results: Database evaluation revealed 172 patients with melanoma of the trunk with follow-up information for at least 6 mounts. Twenty-three patients underwent PMLVA during CLND until March 2018, 29 from April 2018, and 120 subjects underwent CLND without any preventive surgery (control Group). The frequency of SL was significantly lower in both Group 1 (4.3% vs. 24.2%, p = 0.03) and Group 2 (3.5%, p = 0.01). Patients undergoing PMLVA showed a similar recurrence-free periods and overall survival when compared to the control group. Conclusions: PMLVA significantly reduces the frequency of SL both in immediate and delayed CLND. This procedure is safe and does not lead to an increase in length of hospitalization. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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8 pages, 2550 KiB

Open AccessArticle

Lymphatic Complications Prevention and Soft Tissue Reconstruction after Soft Tissue Sarcoma Resection in the Limbs

by Mario F. Scaglioni, Matteo Meroni, Elmar Fritsche and Bruno Fuchs

Medicina 2022, 58(1), 67; https://doi.org/10.3390/medicina58010067 - 2 Jan 2022

Cited by 8 | Viewed by 5087

Abstract

Background and Objectives: The definitive treatment of soft tissue sarcomas (STS) requires a radical surgical removal of the tumor, which often leads to large soft tissue defects. When they are located in the limbs, significant damage to the lymphatic pathways is not uncommon. In the present article, we present different techniques aimed at both reconstructing the defect and restoring sufficient lymph drainage, thus preventing short- and long-term lymphatic complications. Materials and Methods: Between 2018 and 2020, 10 patients presenting a soft tissue defect with lymphatic impairment received a locoregional reconstruction by means of either pedicled or free SCIP flap. Seven patients required a second flap to reach a good dead space obliteration. In six cases, we performed an interpositional flap, namely a soft tissue transfer with lymphatic tissue preservation, and in four cases a lymphatic flow-through flap. In all cases, the cause of the defect was STS surgical excision. The average age was 60.5 years old (ranging 39–84), seven patients were females and six were males. Results: All the patients were successfully treated. In two cases, minor post-operative complications were encountered (infected seroma), which were conservatively managed. No secondary procedures were required. The average follow-up was 8.9 months (ranging 7–12 months). No signs of lymphedema were reported during this time. In all cases, complete range of motion (ROM) and a good cosmetic result were achieved. Conclusions: A reconstructive procedure that aims not only to restore the missing volume, but also the lymphatic drainage might successfully reduce the rate of postoperative complications. Both lymphatic interpositional flaps and lymphatic flow-through flaps could be effective, and the right choice must be done according to each patient’s needs. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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7 pages, 1542 KiB

Open AccessEditor’s ChoiceArticle

Genital Lymphedema and How to Deal with It: Pearls and Pitfalls from over 38 Years of Experience with Unusual Lymphatic System Impairment

by Juste Kaciulyte, Leonardo Garutti, Davide Spadoni, Jonathan Velazquez-Mujica, Luigi Losco, Pedro Ciudad, Marco Marcasciano, Federico Lo Torto, Donato Casella, Diego Ribuffo and Hung-Chi Chen

Medicina 2021, 57(11), 1175; https://doi.org/10.3390/medicina57111175 - 28 Oct 2021

Cited by 21 | Viewed by 8059

Abstract

Background and Objectives: Conservative treatment represents an essential pillar of lymphedema management, along with debulking and physiologic surgeries. Despite the consistent number of treatment options, there is currently no agreement on their indications and possible combinations. When dealing with unusual lymphedema presentation as in the genitalia (Genital Lymphedema—GL), treatment choice becomes even more difficult. The authors aimed to present their targeted algorithm of single and combined treatment modalities for rare GL in order to face this paucity of information. Materials and Methods: Data were collected from a prospectively maintained database since January 1983, and cases of GL that were managed in the authors’ department were selected. Only patients that were treated in the authors’ institution and presented a minimum follow-up of 3 months were admitted to the current study. Results: From January 1983 to July 2021, 19 patients with GL were recruited. All the patients were male, and their ages ranged from 21 to 73 years old (average: 52). Ten cases (52.6%) presented with ISL (International Society of Lymphology) stage I, five (26.3%) were stage II and four (21.1%) were stage III. GL was managed with conservative treatment (12 cases), LVA (LymphaticoVenous Anastomosis) (3) or surgical excision (4). In a mean follow-up of 7.5 years (range: 3 months—11 years), no major complications occurred, and all cases reached improvements in functional and quality of life terms. Conclusions: Contrary to the predominant thought of the necessity to avoid surgery in unusual lymphedema presentations such as GL, they can be managed using targeted multimodal approaches or by adapting well-known procedures in unusual ways to achieve control of disease progression and improve patients’ quality of life. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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11 pages, 1375 KiB

Open AccessArticle

Effects of Intermittent Pneumatic Compression on Lower Limb Lymphedema in Patients with Type 2 Diabetes Mellitus: A Pilot Randomized Controlled Trial

by Alessandro de Sire, Maria Teresa Inzitari, Lucrezia Moggio, Monica Pinto, Giustino de Sire, Marta Supervia, Annalisa Petraroli, Mariangela Rubino, Delia Carbotti, Elena Succurro, Antonio Ammendolia and Francesco Andreozzi

Medicina 2021, 57(10), 1018; https://doi.org/10.3390/medicina57101018 - 25 Sep 2021

Cited by 8 | Viewed by 4349

Abstract

Background and Objectives: Diabetes mellitus type 2 (T2DM) is a chronic disease associated with fluid accumulation in the interstitial tissue. Manual lymphatic drainage (MLD) plays a role in reducing lymphoedema, like intermittent pneumatic compression (IPC). By the present pilot study, we aimed to evaluate the efficacy of a synergistic treatment with MLD and IPC in reducing lower limb lymphedema in T2DM patients. Materials and Methods: Adults with a clinical diagnosis of T2DM and lower limb lymphedema (stage II–IV) were recruited from July to December 2020. Study participants were randomized into two groups: experimental group, undergoing a 1-month rehabilitative program consisting of MLD and IPC (with a compression of 60 to 80 mmHg); control group, undergoing MLD and a sham IPC (with compression of <30 mmHg). The primary outcome was the lower limb lymphedema reduction, assessed by the circumferential method (CM). Secondary outcomes were: passive range of motion (pROM) of hip, knee, and ankle; quality of life; laboratory exams as fasting plasma glucose and HbA1c. At baseline (T0) and at the end of the 1-month rehabilitative treatment (T1), all the outcome measures were assessed, except for the Hb1Ac evaluated after three months. Results: Out of 66 T2DM patients recruited, only 30 respected the eligibility criteria and were randomly allocated into 2 groups: experimental group (n = 15; mean age: 54.2 ± 4.9 years) and control group (n = 15; mean age: 54.0 ± 5.5 years). At the intra-group analysis, the experimental group showed a statistically significant improvement of all outcome measures (p < 0.05). The between-group analysis showed a statistically significant improvement in pROM of the hip, knee, ankle, EQ-VAS, and EQ5D3L index at T1. Conclusions: A multimodal approach consisting of IPC and MLD showed to play a role in reducing lower limb lymphedema, with an increase of pROM and HRQoL. Since these are preliminary data, further studies are needed. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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Review

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14 pages, 791 KiB

Open AccessReview

Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review

by Alessandro de Sire, Luigi Losco, Lorenzo Lippi, Davide Spadoni, Juste Kaciulyte, Gokhan Sert, Paola Ciamarra, Marco Marcasciano, Roberto Cuomo, Alberto Bolletta, Marco Invernizzi and Emanuele Cigna

Medicina 2022, 58(7), 954; https://doi.org/10.3390/medicina58070954 - 19 Jul 2022

Cited by 33 | Viewed by 5673

Abstract

Lymphedema is a chronic disabling condition affecting a growing number of patients worldwide. Although lymphedema is not life-threatening, several reports underlined detrimental consequences in terms of distress, pain, functional impairment, and infections with a relevant decrease in quality of life. Currently, there is no cure, and the therapeutic management of this condition aims at slowing down the disease progression and preventing secondary complications. Early diagnosis is paramount to enhance the effects of rehabilitation or surgical treatments. On the other hand, a multidisciplinary treatment should be truly integrated, the combination of microsurgical and reductive procedures should be considered a valid strategy to manage extremity lymphedema, and rehabilitation should be considered the cornerstone of the multidisciplinary treatment not only for patients not suitable for surgical interventions but also before and after surgical procedures. Therefore, a specialized management of Plastic Reconstructive Surgeons and Physical and Rehabilitative Medicine physicians should be mandatory to address patients’ needs and optimize the treatment of this disabling and detrimental condition. Therefore, the aim of this review was to characterize the comprehensive management of lymphedema, providing a broad overview of the potential therapy available in the current literature to optimize the comprehensive management of lymphedema and minimize complications. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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18 pages, 6523 KiB

Open AccessReview

The Lymphatic System in Breast Cancer: Anatomical and Molecular Approaches

by Gianfranco Natale, Michael E. J. Stouthandel, Tom Van Hoof and Guido Bocci

Medicina 2021, 57(11), 1272; https://doi.org/10.3390/medicina57111272 - 19 Nov 2021

Cited by 12 | Viewed by 4630

Abstract

Breast cancer is one of the most important causes of premature mortality among women and it is one of the most frequently diagnosed tumours worldwide. For this reason, routine screening for prevention and early diagnosis is important for the quality of life of patients. Breast cancer cells can enter blood and lymphatic capillaries, then metastasizing to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Rather than at the primary site, they seem to enter the systemic circulation mainly through the sentinel lymph node and the biopsy of this indicator can influence the axillary dissection during the surgical approach to the pathology. Furthermore, secondary lymphoedema is another important issue for women following breast cancer surgical treatment or radiotherapy. Considering these fundamental aspects, the present article aims to describe new methodological approaches to assess the anatomy of the lymphatic network in the axillary region, as well as the molecular and physiological control of lymphatic vessel function, in order to understand how the lymphatic system contributes to breast cancer disease. Due to their clinical implications, the understanding of the molecular mechanisms governing lymph node metastasis in breast cancer are also examined. Beyond the investigation of breast lymphatic networks and lymphatic molecular mechanisms, the discovery of new effective anti-lymphangiogenic drugs for future clinical settings appears essential to support any future development in the treatment of breast cancer. Full article

(This article belongs to the Special Issue Vasorum Lymphaticorum: From the Discovery of the Lymphatic System to the New Perspectives in Microsurgical Reconstruction and Patient Rehabilitation)

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