Longitudinal monitoring of the head and neck lymphatics in response to surgery and radiation

Rasmussen, John C.; Tan, I-Chih; Naqvi, Syeda Uzma; Aldrich, Melissa B.; Maus, Erik A.; Blanco, Angel I.; Karni, Ron J.; Sevick‐Muraca, Eva M.

doi:10.1002/hed.24750

Cited by 24 publications

(34 citation statements)

References 23 publications

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“…To date, we have not imaged dermal backflow in the external lymphatics of treatment-naive HNC patients with known or suspected LN metastases, probably because these external lymphatics are typically not in the same lymphatic watershed directly draining interior oropharynx, larynx, and oral cancers. However, in preliminary studies of internal lymphatic drainage of treatment-naive HNC patients, few exhibited drainage into the lympho-jugular chain after mucosal administration of ICG [29], as was seen in normal-health subjects (Figure 4 above) [27]. This observation is preliminary and needs more carefully controlled studies to underscore changes in internal lymphatic drainage from the cranium with head and neck cancer progression.…”

Section: The Role Of Lymph Node Dissection and Rt On Lymphatic Functionmentioning

confidence: 93%

“…This administration enables imaging of the ipsilateral lympho-jugular lymphatic chain that drains into the cervical ( Figure 5a) and supraclavicular LNs ( Figure 5b) when subjects are sitting upright. The mucosal lymphatics that line the throat are impacted in head and neck cancer treatments and are commonly referred to as "internal lymphatics," as they drain near the internal jugular vein [29]. Their dysfunction after cancer treatment may be responsible for swelling of the throat and base of tongue as well as for impairing speaking, breathing, and swallowing in head and neck cancer survivors.…”

Section: Anatomy and Function Of Cranial/cervical Lymphaticsmentioning

confidence: 99%

“…(a) (b) (c) In contrast to ICG intramucosally injected in the oral cavity, ICG intradermally administered on the face, generally fore and aft of the ear, chin, cheek, lateral forehead, and along the jawline, drains through the superficial or "external lymphatics" (Figure 5c). These external lymphatics include the submental nodes that drain the skin of the chin, lower lip, floor of the mouth, and anterior portion of the tongue; the supra-and sub-mandibular nodes that drain the skin and mucosa of the cheeks, upper and lower lips, and floor of the mouth; the posterior nodes that drain lateral and posterior neck and the nasopharynx, oropharynx, and thyroid; and the superficial and deep cervical nodes that receive drainage from above [29]. These lymphatics may become compromised with surgical incision and RT, resulting in swelling of lips, under the chin, along the jawline, cheeks, and eyelids, commonly recognized as head and neck LE.…”

Section: Anatomy and Function Of Cranial/cervical Lymphaticsmentioning

confidence: 99%

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The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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Breast-cancer-acquired lymphedema is routinely diagnosed from the appearance of irreversible swelling that occurs as a result of lymphatic dysfunction. Yet in head and neck cancer survivors, lymphatic dysfunction may not always result in clinically overt swelling, but instead contribute to debilitating functional outcomes. In this review, we describe how cancer metastasis, lymph node dissection, and radiation therapy alter lymphatic function, as visualized by near-infrared fluorescence lymphatic imaging. Using custom gallium arsenide (GaAs)-intensified systems capable of detecting trace amounts of indocyanine green administered repeatedly as lymphatic contrast for longitudinal clinical imaging, we show that lymphatic dysfunction occurs with cancer progression and treatment and is an early, sub-clinical indicator of cancer-acquired lymphedema. We show that early treatment of lymphedema can restore lymphatic function in breast cancer and head and neck cancer patients and survivors. The compilation of these studies provides insights to the critical role that the lymphatics and the immune system play in the etiology of lymphedema and associated co-morbidities.

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Section: The Role Of Lymph Node Dissection and Rt On Lymphatic Functionmentioning

confidence: 93%

Section: Anatomy and Function Of Cranial/cervical Lymphaticsmentioning

confidence: 99%

Section: Anatomy and Function Of Cranial/cervical Lymphaticsmentioning

confidence: 99%

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The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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“…This latter result may be striking as previous HNL studies demonstrated persistent backflow during months of observation. 6 Future studies evaluating lymphatic response to longer durations of treatment and its durability could definitively determine whether advanced pneumatic compression treatment can ameliorate all backflow and potentially mitigate or prevent HNL.…”

Section: Impact Of 2 Weeks Of Treatmentmentioning

confidence: 99%

Head and Neck Lymphedema: Treatment Response to Single and Multiple Sessions of Advanced Pneumatic Compression Therapy

Gutiérrez

Karni

Naqvi

et al. 2019

Otolaryngol.--head neck surg.

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Ten head and neck cancer survivors diagnosed with head and neck lymphedema (HNL) were imaged using nearinfrared fluorescence lymphatic imaging (NIRFLI) prior to and immediately after an initial advance pneumatic compression device treatment and again after 2 weeks of daily athome use. Images assessed the impact of pneumatic compression therapy on lymphatic drainage. Facial composite measurement scores assessed reduction/increase in external swelling, and survey results were obtained. After a single pneumatic compression treatment, NIRFLI showed enhanced lymphatic uptake and drainage in all subjects. After 2 weeks of daily treatment, areas of dermal backflow disappeared or were reduced in 6 of 8 subjects presenting with backflow. In general, reductions in facial composite measurement scores tracked with reductions in backflow and subject-reported improvements; however, studies are needed to determine whether longer treatment durations can be impactful and whether advanced pneumatic compression can be used to ameliorate backflow characteristic of HNL.

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“…While ICG is contraindicated for intrathecal injection in humans, we rationalize that by visualizing lymphatic drainage from the palatine tonsil, the drainage pathway of CSF through the head and neck region could likewise be visualized. Previously, we used NIRF lymphatic imaging to longitudinally evaluate deep internal lymphatic drainage in head and neck cancer survivors who experienced LN dissection as part of their cancer treatment (Rasmussen, Tan, et al, 2017). Injections in the palatine tonsils were chosen to demark the deep lymphatic drainage pathways that were, more often than not, undetected using the technique, presumably because of the history of cancer and its treatment, inconsistency of the injection depth, or the relatively short imaging time post injection.…”

Section: Discussionmentioning

confidence: 99%

Assessing lymphatic route of CSF outflow and peripheral lymphatic contractile activity during head‐down tilt using near‐infrared fluorescence imaging

et al. 2020

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Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight‐associated neuro‐ocular syndrome (SANS), a problem that limits long‐duration spaceflight. We used near‐infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head‐down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot study was conducted in human volunteers to evaluate the effect of gravity on the flow of lymph through these deep cervical lymphatics. Injected into the palatine tonsils, ICG was imaged draining into deep jugular lymphatic vessels and subsequent cervical lymph nodes. NIRFLI was performed under HDT, sitting, and supine positions. NIRFLI shows that lymphatic drainage through pathways shared by CSF outflow are dependent upon gravity and are impaired under short‐term HDT. In addition, lymphatic contractile rates were evaluated from NIRFLI following intradermal ICG injections of the lower extremities. Lymphatic contractile activity in the legs was slowed in the gravity neutral, supine position, but increased under the influence of gravity regardless of whether its force direction opposed (sitting) or favored (HDT) lymphatic flow toward the heart. These studies evidence the role of a lymphatic contribution in SANS.

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Longitudinal monitoring of the head and neck lymphatics in response to surgery and radiation

Abstract: The external lymphatics undergo transient changes during and weeks after lymph node dissection and radiotherapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1177-1188, 2017.

Cited by 24 publications

References 23 publications

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Head and Neck Lymphedema: Treatment Response to Single and Multiple Sessions of Advanced Pneumatic Compression Therapy

Assessing lymphatic route of CSF outflow and peripheral lymphatic contractile activity during head‐down tilt using near‐infrared fluorescence imaging

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