Special Issue "Cancer Related Lymphedema"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 30 June 2020.

Special Issue Editors

Dr. Babak J. Mehrara
Website
Guest Editor
Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Interests: Secondary lymphedema; inflammation; fibrosis; T cells; drug development; surgical treatment of lymphedema; pathophysiology of lymphedema
Special Issues and Collections in MDPI journals
Dr. Raghu P. Kataru
Website
Guest Editor
Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Interests: Lymphangiogenesis; inflammatory regulation; immune responses; fibrosis; secondary lymphedema; T cells; lymphatic trafficking
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The last decade has been notable in terms of advances in medical and surgical treatment of lymphedema resulting from cancer treatment (secondary lymphedema). This is particularly important since secondary lymphedema is a morbid and life-long disease that affects a large number of patients treated for solid cancers including breast cancer, melanoma, urologic malignancies, gynecological tumors, and sarcomas. More than 1 in 5 patients treated for these conditions develop secondary lymphedema making lymphedema the most common long-term complication of solid cancer treatment. In fact, it is estimated that nearly 6 million Americans suffer from this disease with resultant significant morbidity and biomedical costs.

The advances in medical and surgical treatments of this disease have been made possible by improvements in surgical techniques and key discoveries that have shed light on the pathophysiology of lymphedema. Understanding the mechanisms that regulate lymphatic degeneration following lymphatic injury has led to clinical trials of medical therapies aiming to reverse these pathways. Indeed, preclinical studies have shown the important role of chronic inflammation, changes in lymphatic smooth muscle cells, tissue fibrosis, lymphatic pumping, and regulation of collateral lymphatic channels.

Similarly, surgical therapies such as lymph node transplantation and lymphovenous bypass have been developed to reverse the pathologic changes of lymphedema and show promise in some settings. These studies have highlighted the importance of presurgical lymphatic imaging, development of novel surgical techniques, and unique challenges in quantifying outcomes following surgery.

This Special Issue aims to summarize our current understanding of the pathophysiology of secondary lymphedema and how this knowledge is used in designing novel medical and surgical therapies for this disease.

Dr. Babak J. Mehrara
Dr. Raghu P. Kataru
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • secondary lymphedema
  • breast cancer related lymphedema
  • cancer related lymphedema
  • lymph node dissection
  • iatrogenic lymphatic injury
  • pathophysiology
  • inflammation
  • lymphangiogenesis
  • lymphatic pumping
  • lymphatic leakiness
  • lymphatic smooth muscle cells
  • fibrosis
  • T cells
  • surgical treatment of lymphedema
  • lymphovenous bypass
  • lymph node transplantation
  • liposuction
  • surgical outcomes of lymphedema

Published Papers (5 papers)

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Research

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Open AccessArticle
Real-Time Visualization of the Mascagni-Sappey Pathway Utilizing ICG Lymphography
Cancers 2020, 12(5), 1195; https://doi.org/10.3390/cancers12051195 - 08 May 2020
Abstract
Background: Anatomic variations in lymphatic drainage pathways of the upper arm may have an important role in the pathophysiology of lymphedema development. The Mascagni–Sappey (M–S) pathway, initially described in 1787 by Mascagni and then again in 1874 by Sappey, is a lymphatic drainage [...] Read more.
Background: Anatomic variations in lymphatic drainage pathways of the upper arm may have an important role in the pathophysiology of lymphedema development. The Mascagni–Sappey (M–S) pathway, initially described in 1787 by Mascagni and then again in 1874 by Sappey, is a lymphatic drainage pathway of the upper arm that normally bypasses the axilla. Utilizing modern lymphatic imaging modalities, there is an opportunity to better visualize this pathway and its potential clinical implications. Methods: A retrospective review of preoperative indocyanine green (ICG) lymphangiograms of consecutive node-positive breast cancer patients undergoing nodal resection was performed. Lymphography targeted the M-S pathway with an ICG injection over the cephalic vein in the lateral upper arm. Results: In our experience, the M-S pathway was not visualized in 22% (n = 5) of patients. In the 78% (n = 18) of patients where the pathway was visualized, the most frequent anatomic destination of the channel was the deltopectoral groove in 83% of patients and the axilla in the remaining 17%. Conclusion: Our study supports that ICG injections over the cephalic vein reliably visualizes the M-S pathway when present. Further study to characterize this pathway may help elucidate its potential role in the prevention or development of upper extremity lymphedema. Full article
(This article belongs to the Special Issue Cancer Related Lymphedema)
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Open AccessArticle
Preoperative Assessment of Upper Extremity Secondary Lymphedema
Cancers 2020, 12(1), 135; https://doi.org/10.3390/cancers12010135 - 06 Jan 2020
Cited by 1
Abstract
Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema. Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment [...] Read more.
Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema. Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment of secondary lymphedema. Lymphedema evaluation included limb volume measurements, bio-impedance, indocyanine green lymphography, lymphoscintigraphy, magnetic resonance angiography, lymphedema life impact scale (LLIS) and upper limb lymphedema 27 (ULL-27) questionnaires. Results: 118 patients were evaluated. Limb circumference underestimated lymphedema compared to limb volume. Bioimpedance (L-Dex) scores highly correlated with limb volume excess (r2 = 0.714, p < 0.001). L-Dex scores were highly sensitive and had a high positive predictive value for diagnosing lymphedema in patients with a volume excess of 10% or more. ICG was highly sensitive in identifying lymphedema. Lymphoscintigraphy had an overall low sensitivity and specificity for the diagnosis of lymphedema. MRA was highly sensitive in diagnosing lymphedema and adipose hypertrophy as well as useful in identifying axillary vein obstruction and occult metastasis. Patients with minimal limb volume difference still demonstrated significantly impaired quality of life. Conclusion: Preoperative assessment of lymphedema is complex and requires multimodal assessment. MRA, L-Dex, ICG, and PROMs are all valuable components of preoperative assessment. Full article
(This article belongs to the Special Issue Cancer Related Lymphedema)
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Open AccessArticle
Lower Extremity Lymphedema in Gynecologic Cancer Patients: Propensity Score Matching Analysis of External Beam Radiation versus Brachytherapy
Cancers 2019, 11(10), 1471; https://doi.org/10.3390/cancers11101471 - 30 Sep 2019
Cited by 1
Abstract
The goal of this study is to compare the risk of lower extremity lymphedema (LEL) between pelvic external beam radiation therapy (EBRT) and vaginal brachytherapy, and to identify risk factors for LEL in gynecologic cancer patients treated with adjuvant radiation therapy (RT) after [...] Read more.
The goal of this study is to compare the risk of lower extremity lymphedema (LEL) between pelvic external beam radiation therapy (EBRT) and vaginal brachytherapy, and to identify risk factors for LEL in gynecologic cancer patients treated with adjuvant radiation therapy (RT) after radical surgery. A total of 263 stage I–III gynecologic cancer patients who underwent adjuvant RT were retrospectively reviewed. One-to-one case-matched analysis was conducted with propensity scores generated from patient, tumor, and treatment characteristics. Using the risk factors found in this study, high- and low-risk groups were identified. With a median follow-up of 36.0 months, 35 of 263 (13.3%) patients developed LEL. In multivariate analysis, laparoscopic surgery (HR 2.548; p = 0.024), harvesting more than 30 pelvic lymph nodes (HR 2.246; p = 0.028), and para-aortic lymph node dissection (PALND, HR 2.305; p = 0.014) were identified as independent risk factors for LEL. After propensity score matching, the LEL incidence of the brachytherapy group was significantly lower than the EBRT group (p = 0.025). In conclusion, high-risk patients with risk factors such as laparoscopic surgery, harvesting more than 30 pelvic lymph nodes, PALND, and adjuvant pelvic EBRT require closer observation for LEL. Full article
(This article belongs to the Special Issue Cancer Related Lymphedema)
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Review

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Open AccessReview
Systematic Review of Patient-Reported Outcomes following Surgical Treatment of Lymphedema
Cancers 2020, 12(3), 565; https://doi.org/10.3390/cancers12030565 - 29 Feb 2020
Abstract
Introduction: Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of [...] Read more.
Introduction: Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of this study was to conduct a systematic review of outcomes and utilization of PROMs following surgical treatment of lymphedema. Methods: A literature search of four databases was performed up to and including March, 2019. Studies included reported on QOL outcomes after physiologic procedures, defined as either lymphovenous bypass (LVB) or vascularized lymph node transplant (VLNT), to treat upper and/or lower extremity primary or secondary lymphedema. Results: In total, 850 studies were screened—of which, 32 studies were included in this review. Lymphovenous bypass was the surgical intervention in 16 studies, VLNT in 11 studies, and both in 5 studies. Of the 32 total studies, 16 used validated survey tools. The most commonly used PROM was the lymph quality of life measure for limb lymphedema (LYMQOL) (12 studies). In the remaining four studies, the upper limb lymphedema 27 scale (ULL27), the short form 36 questionnaire (SF-36), the lymphedema functioning, disability and health questionnaire (Lymph-ICF), and lymphedema life impact scale (LLIS) were each used once. QOL improvement following surgical treatment was noted in all studies. Conclusions: Physiologic surgical treatment of lymphedema results in improved QOL outcomes in most patients. The use of validated PROM tools is increasing but there is no current consensus on use. Future research to evaluate the psychometric properties of PROMs in lymphedema is needed to guide the development and use of lymphedema-specific tools. Full article
(This article belongs to the Special Issue Cancer Related Lymphedema)
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Other

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Open AccessCommentary
Anatomical Theories of the Pathophysiology of Cancer-Related Lymphoedema
Cancers 2020, 12(5), 1338; https://doi.org/10.3390/cancers12051338 - 23 May 2020
Abstract
Lymphoedema is a well-known concern for cancer survivors. A crucial issue in lymphoedema is that we cannot predict who will be affected, and onset can occur many years after initial cancer treatment. The variability of time between cancer treatment and lymphoedema onset is [...] Read more.
Lymphoedema is a well-known concern for cancer survivors. A crucial issue in lymphoedema is that we cannot predict who will be affected, and onset can occur many years after initial cancer treatment. The variability of time between cancer treatment and lymphoedema onset is an unexplained mystery. Retrospective cohort studies have investigated the risk factors for lymphoedema development, with extensive surgery and the combination of radiation and surgery identified as common high-risk factors. However, these studies could not predict lymphoedema risk in each individual patient in the early stages, nor could they explain the timing of onset. The study of anatomy is one promising tool to help shed light on the pathophysiology of lymphoedema. While the lymphatic system is the area least investigated in the field of anatomical science, some studies have described anatomical changes in the lymphatic system after lymph node dissection. Clinical imaging studies in lymphangiography, lymphoscintigraphy and indocyanine green (ICG) fluorescent lymphography have reported post-operative anatomical changes in the lymphatic system, including dermal backflow, lymphangiogenesis and creation of alternative pathways via the deep and torso lymphatics, demonstrating that such dynamic anatomical changes contribute to the maintenance of lymphatic drainage pathways. This article presents a descriptive review of the anatomical and imaging studies of the lymphatic system in the normal and post-operative conditions and attempts to answer the questions of why some people develop lymphoedema after cancer and some do not, and what causes the variability in lymphoedema onset timing. Full article
(This article belongs to the Special Issue Cancer Related Lymphedema)
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