Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis

Imai, Hirofumi; Kawase, Takakazu; Yoshida, Shuhei; Mese, Toshiro; Roh, Solji; Fujita, Asuka; Uchiki, Toshio; Sasaki, Ayano; Nagamatsu, Shogo; Takazawa, Atsushi; Ichinohe, Tatsuo; Koshima, Isao

doi:10.1016/j.isci.2023.106822

Cited by 9 publications

(5 citation statements)

References 57 publications

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“…Nonetheless, some scholars have speculated that LVA may not be sufficient for treating chronic lymphedema patients, particularly those in the later stages of the International Society of Lymphology (ISL) lymphedema classification [ 26 , 27 , 28 , 29 , 30 ]. Past pathophysiological investigations have demonstrated that chronic inflammation and lymphatic fluid stagnation lead to the breakdown of the lymphatic vessels’ pumping function and programmed cell death in lymphatic endothelial cells [ 31 , 32 , 33 ]. This, in turn, induces tissue fibrosis and gradual pathological alterations in the lymphatic lumen until the lymphatic vessel becomes hardened and nonfunctional.…”

Section: Discussionmentioning

confidence: 99%

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema

Park,

Choi,

Beom

et al. 2023

Medicina

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Background and Objectives: When considering surgery for patients with breast cancer-related lymphedema (BCRL), it is crucial to determine which surgery will be most effective for the patient and establish the indications for each surgery. Our study retrospectively compared the results of preoperative noncontrast MR lymphangiography (NMRL) performed on the lymphedematous limb of patients before surgery, with the aim of analyzing whether preoperative NMRL can be used as a criterion for determining the type of surgery. Materials and Methods: From January 2020 to June 2022, a total of 138 patients with lymphedema underwent surgery at Seoul National University Bundang Hospital. All patients underwent preoperative NMRL imaging and were classified into stages 1–3 based on the MRI severity index using the authors’ previous reference. Three types of surgery, LVA, LVA + liposuction, and LVA + VLNT, were conducted on all patients. The effectiveness of the surgery was evaluated one year postoperatively using the interlimb volume difference before and after surgery, the fluid volume of the edematous limb measured by bioimpedance spectroscopy, and the subjective satisfaction of the patients through the Lymph Q questionnaire. Results: In this study, out of a total of 138 patients, 26 (19%) were MRI stage 1, 62 (45%) were stage 2, and 50 (36%) were stage 3. Of the 83 patients who underwent LVA surgery, the greatest decrease in interlimb volume difference was observed in stage 2 patients, and subjective satisfaction was also the most effective in stage 2. In the case of LVA + liposuction patients, a significant volume decrease and a high satisfaction were observed in stage 3 patients. In the case of LVA + VLNT patients, there was no difference in volume decrease according to the stage, but a greater decrease in body fluid volume was observed as the MRI severity index score increased through BIA. Conclusions: In conclusion, this study demonstrates that NMRL imaging is a useful modality for determining the most effective surgical method and predicting the surgical outcome in patients with lymphedema. This highlights the importance of using NMRL in the treatment planning of lymphedema patients.

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Section: Discussionmentioning

confidence: 99%

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema

Park,

Choi,

Beom

et al. 2023

Medicina

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“…One-year post-operative decrease in IFN-γ and IL-17A expression, increased T-cell receptor diversity. Downregulation of PD-1, Tim-3, PD-1 + Tim-3 + on CD4 + and CD8 + T cells [121].…”

Section: Surgical Interventionsmentioning

confidence: 99%

“…Changes were further associated with decreased collagen type I deposition and TGFβ-1 expression, implicating antifibrotic activity six months post-lymphaticovenous anastomosis [120]. More recent work has focused specifically on characterizing the peripheral T-cell profile in lymphedema patients after lymphaticovenous anastomosis [121]. A one-year pre-post comparative study of lymphedematous tissue exhaustion and inflammation demonstrated that IFN-γ and IL-17A levels in CD4 + cells were downregulated following lymphaticovenous anastomosis, while T-cell receptor diversity increased post-operatively, a measure that is typically low in lymphedematous tissues.…”

Section: Surgical Interventionmentioning

confidence: 99%

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention

Bowman,

Rockson

2024

IJMS

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Lymphedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. Despite early hypotheses identifying lymphedema as a disease of mechanical lymphatic disruption alone, the progressive inflammatory nature underlying this condition is now well-established. In this review, we provide an overview of the various inflammatory mechanisms that characterize lymphedema development and progression. These mechanisms contribute to the acute and chronic phases of lymphedema, which manifest clinically as inflammation, fibrosis, and adiposity. Furthermore, we highlight the interplay between current therapeutic modalities and the underlying inflammatory microenvironment, as well as opportunities for future therapeutic development.

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“…Lymphaticovenous anastomosis is, as the name suggests, a technique where venules and lymphatic vessels are anastomosed, requiring supermicrosurgical technique due to the diameter of the vessels ( 12 ). While the idea started as a shunt that bypasses the area of obstruction by draining excess lymphatic fluid into the venous system ( 13 ), recent research provides a more nuanced view of the systemic effects including normalization of lymphedema-related changes in T cell profile after LVA surgery ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Surgical treatments of lymphedema—a literature review on robot-assisted lymphovenous anastomosis (LVA)

Engström,

Mani

2024

Gland Surg

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Background and Objective Lymphedema is a common issue after surgery and oncologic treatment, affecting millions of people worldwide. A better understanding of the condition has provided an increasing possibility of a tailormade treatment plan, and with improvement in surgical technique, we now have several surgical treatments to offer, including the lymphovenous anastomosis (LVA). Considering the size of lymph vessels used for LVA, sometimes as small as 0.3 mm, there is a need for improvement of the technical aspects of the procedures. This paper explores the potential of robotic assistance in LVA surgery as an innovative approach to overcome the limitations of human dexterity. Methods A literature review was performed on 2023-12-22 using PubMed, Cochrane, and Embase databases to identify all previous publications on robotic LVA surgery, resulting in a total of 65 publications. Original publications in English were considered and after selection, a total of 5 publications were included in the review. Key Content and Findings Two surgical systems used in clinical practice were identified, the MUSA (Microsure) and the Symani Surgical System (Medical Microinstruments). Common topics for discussion include the increased precision the robot assistance provides, clinical outcomes, ergonomics, and the learning curve for aspiring robot surgeons. Anastomosis times were generally found to be longer initially, but several authors note that there is a steep learning curve with rapidly decreasing times with an increasing number of procedures. Overall clinical outcomes were comparable to those using manual anastomosis. Conclusions The use of robotics in LVA surgery, has shown promising results through clinical studies. Robotic assistance can help augment the technical capacity of a surgeon through motion scaling and tremor filtration, facilitating the most delicate steps of the LVA. The learning curve is steep, and the technique can hopefully make microsurgical reconstructions available to a broader number of patients. Further development can include haptic feedback, structured training programs, and cost optimization through dissemination of the technology.

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Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis

Cited by 9 publications

References 57 publications

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention

Surgical treatments of lymphedema—a literature review on robot-assisted lymphovenous anastomosis (LVA)

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