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Current and Future Implications of Lymphedema Surgery in Head and Neck Reconstruction
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Liposuction for treatment of lymphedema is an effective and time-tested treatment. However, as there is a fear regarding further lymphatic damage caused by liposuction, we objectively compared lymphatic function pre- and post-liposuction. All patients with solid-predominant lymphedema who were treated during the study period of June 2014 and November 2018 were included. Patients were assessed using patient-reported baselines/outcomes, lymphedema- specific quality of life scale (LYMQOL), limb circumference/volume measurements, and indocyanine green lymphography (ICGL) preoperatively and at predefined postoperative time intervals. Fifty-seven limbs from 41 patients were included. Mean lipoaspirate volumes were 2035 mL, 5385 mL, and 3106 mL for the arm, thigh, and leg, respectively with a mean adipose fraction of the lipoaspirate of 71%. All patients underwent redundant skin excision with the “flying squirrel” technique. The mean follow-up was 10.7 months (range 3 – 48 months) with a mean limb volume reduction of 32.2% and all patients reporting satisfactory relief of symptoms. All showed statistically significant improvement in LYMQOL in symptoms, appearance, and function. On ICGL, none showed worsened lymphatic drainage, rather, all showed improved lymph drainage. Furthermore, the improved lymph drainage was found to be progressive during the study period in all patients. Our study results demonstrate that treating extremity lymphedema with liposuction does not worsen lymphatic function and in fact, paradoxically, it induces progressive improvement in lymph drainage.
Supermicrosurgical lymphaticovenular anastomosis (LVA) is the most sought-after procedure among lymphedema patients. However, the same enthusiasm is currently not shared among lymphedema surgeons due to the lackluster results of LVA. The common unfavorable experience with this famed procedure is at least partially caused by the difficulty in finding the lymph vessels. We share our time-tested indocyanine green-based lymph vessel mapping technique, which has helped us establish LVA as our procedure for all fluid-predominant lymphedema.
Purpose
This systematic review aimed to provide a comprehensive overview of the validity and reliability of existing measurement instruments for quantifying head and neck lymphedema.
Methods
Four databases were searched on January 31st, 2022. The COnsensus-based Standards for selecting health Measurement INstruments (COSMIN) checklists were used for the risk of bias (ROB) assessment.
Results
Out of 3362 unique records, eight studies examined the reliability and validity of five measurement instruments of which one patient reported outcome. The Patterson scale for internal lymphedema and the patient reported head and neck external lymphedema and fibrosis (LIDS-H&N) demonstrated validity and reliability. For external lymphedema, none of the instruments had good reliability for all measuring points.
Conclusion
There is a lack of sufficiently reliable and valid measurement instruments for external head and neck lymphedema. The Patterson scale and the patient reported LIDS-H&N seem reliable for clinical practice and research.
We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer’s disease. We sort existing models into broad categories by anatomical function: perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, and links to neuronal activity. Needs and opportunities for future work are highlighted wherever possible; new models, expanded models, and novel experiments to inform models could all have tremendous value for advancing the field.
Early surgical intervention for lymphedema can delay, prevent, and even reverse lymphatic degeneration. Vascularized lymph vessel transplant (VLVT) has emerged as an alternative to vascularized lymph node transplant (VLNT) for the treatment of advanced, fluid-predominant lymphedema, providing highly favorable outcomes with reduced donor-site complications. Lymphaticovenular anastomosis (LVA) has traditionally been reserved for early disease. However, technical refinements have improved its results and expanded its efficacy, creating an overlap between the indications for VLVT/VLNT and LVA. This article describes our technical approach to VLVT and LVA and explores the nuances of treatment selection in the light of their shifting indications.
Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.
Facial edemas not secondary to surgery and/or radiotherapy for head and neck cancer are relatively uncommon. Our aim is to report a retrospective analysis of the lymphoscintigraphic and SPECT-CT investigations obtained in patients with such facial edema. Retrospective review of exams (planar imagings in all and with SPECT-CT in 5) obtained after the subcutaneous injection of 99mTc HSA Nanosized colloids between the eyebrows in five men and seven women. Four main lymphatic pathways were identified on sequential planar imagings: para-nasal left and right and supra- ocular left and right. For eleven patients, the absence of visualization of lymphatic drainage and/or their delayed appearance correlated well with the localisation of the edematous areas. In two patients with post-traumatic and post- surgical edemas, SPECT-CT showed one deep left sided cervical lymph node (LN) in front of the first cervical vertebra. This lymphoscintigraphic approach represents a simple and valuable way to assess the lymphatic drainage pathways of the face and to establish the diagnosis of facial lymphedema.
Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD. Reduced meningeal lymphatic flow detected in patients with idiopathic Parkinson’s disease compared to patients with atypical Parkinsonian disorders and cognitively normal controls.
Background and aims
Hepatic encephalopathy (HE) is a serious neurological complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE.
Methods
A 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated using archived GSE41919. Motor function of rats was assessed by the rotarod test. AAV8-VEGF-C was injected into the cisterna magna of HE rats one day after surgery to induce meningeal lymphangiogenesis.
Results
Cirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex(P < .001) as well as increased neuroinflammation as indicated by significant increases in IL-1β, INFγ, TNFα and Iba1 expression in at least one of the three regions of the cortex. Motor function was also impaired in rats with HE(P < .05). Human brains of cirrhotic patients with HE also exhibited upregulation of pro-inflammatory genes(NF-κβ, Iba1, TNFα and IL-1β)(n=6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis(P = .035) and tracer dye uptake in the anterior and middle regions of the cortex(P = .006 & .003, respectively), their corresponding meninges(P = .086 & .006, respectively) and the draining lymph nodes(P = .02). Further, AAV8-VEGF-C decreased microglia activation(P < .001) and neuroinflammation, and ameliorated motor dysfunction(P = .024).
Conclusion
Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.
Dynamic contrast-enhanced magnetic resonance imaging (MRI) for tracking glymphatic system transport with paramagnetic contrast such as gadoteric acid (Gd-DOTA) administration into cerebrospinal fluid (CSF) requires pre-contrast data for proper quantification. Here we introduce an alternative approach for glymphatic system quantification in the mouse brain via T1 mapping which also captures drainage of Gd-DOTA to the cervical lymph nodes. The Gd-DOTA injection into CSF was performed on the bench after which the mice underwent T1 mapping using a 3D spoiled gradient echo sequence on a 9.4 T MRI. In Ketamine/Xylazine (KX) anesthetized mice, glymphatic transport and drainage of Gd-DOTA to submandibular and deep cervical lymph nodes was demonstrated as 25–50% T1 reductions in comparison to control mice receiving CSF saline. To further validate the T1 mapping approach we also verified increased glymphatic transport of Gd-DOTA transport in mice anesthetized with KX in comparison with ISO. The novel T1 mapping method allows for quantification of glymphatic transport as well as drainage to the deep and superficial cervical lymph nodes. The ability to measure glymphatic transport and cervical lymph node drainage in the same animal longitudinally is advantageous and time efficient and the coupling between the two systems can be studied and translated to human studies.
PurposeLymphedema associated with head and neck cancer (HNC) therapy causes adverse clinical outcomes. Standard treatment includes professionally administered complete decongestive therapy (CDT). Cost and availability of trained therapists are known barriers to therapy. Advanced pneumatic compression devices (APCD) may address these issues. A randomized, wait-list controlled trial was undertaken to evaluate an APCD in post-treatment HNC patients with lymphedema.Material and methodsEligible patients had completed treatment for HNC, were disease free, and had lymphedema at enrollment. Participants were randomized to wait-list lymphedema self-management (standard of care) or lymphedema self-management plus the use of the APCD bid. Safety (CTCAE V4.0) and feasibility were primary endpoints; secondary endpoints included efficacy measure by objective examination and patient reported outcomes (symptoms, quality of life, function), adherence barriers, and satisfaction. Assessments were conducted at baseline and weeks 4 and 8.ResultsForty-nine patients were enrolled (wait-list n = 25; intervention n = 24). In total, forty-three patients completed the study. No device-related Serious Adverse Events were reported. Most patients used the APCD once per day, instead of the prescribed twice per day, citing time related factors as barriers to use. APCD use was associated with significant improvement in perceived ability to control lymphedema (p = 0.003) and visible external swelling (front view p < 0.001, right view p = 0.004, left p = 0.005), as well as less reported pain.Conclusion
This trial supports the safety and feasibility of the APCD for the treatment of secondary lymphedema in head and neck cancer patients. In addition, preliminary data supports efficacy.
Objectives
Tape measurement is a commonly used method in the clinical assessment of lymphedema. However, few studies have assessed the precision and reliability of tape measurement in assessing head and neck lymphedema. This study aimed to evaluate the reliability and precision of using tape measurement, performed by different evaluators, for the assessment of head and neck lymphedema.
Methods
This study was conducted at a tertiary care cancer hospital. Between January and December 2019, 50 patients with head and neck cancers and 50 normal subjects were enrolled. Each subject was examined using tape measurements for 7 point-to-point distances of facial landmarks, 3 circumferences of the neck (upper, middle, and lower), and 2 circumferences of the face (vertical and oblique) by 3 random examiners. Test precision and reliability were assessed with the within-subject standard deviation (Sw) and intra-class correlation coefficient (ICC), respectively.
Results
Overall, the standard deviation of the tape measurements varied in the range of 4.6 mm to 18.3 mm. The measurement of distance between the tragus and mouth angle (Sw: 4.6 mm) yielded the highest precision, but the reliability (ICC: 0.66) was moderate. The reliabilities of neck circumference measurements (ICC: 0.90–0.95) were good to excellent, but the precisions (Sw: 8.3–12.3 mm) were lower than those of point-to-point facial measurements (Sw: 4.6–8.8 mm).
Conclusions
The different methods of tape measurements varied in precision and reliability. Thus, clinicians should not rely on a single measurement when evaluating head and neck lymphedema.
One of the sequelae of head and neck cancer treatment is secondary lymphedema, with important impact on breathing, swallowing and vocal functions. The aim of the study was to assess the presence, staging characteristics and relationship of external and internal lymphedema and dysphagia after head and neck cancer treatment. The MDACC Lymphedema Rating Scale in Head and Neck Cancer was employed for the assessment and staging of face and neck lymphedema; the Radiotherapy Edema Scale for internal lymphedema; and a fiberoptic endoscopic evaluation of swallowing (FEES) for swallowing. The sample consisted of 46 patients with a diagnosis of head and neck cancer. Lymphedema was detected in 97.8% (45) of the evaluations with predominance of the composite type (73.9%—34). A high percentage of external lymphedema of the neck (71.7%—33) and submandibular (63%—29) were detected, with predominance of the more advanced levels. Internal edema was found in almost all structures and spaces at moderate/severe level. At FEES, residue (higher percentage in valleculae and pyriform sinus), penetration and aspirations were observed. The residue was detected in higher occurrence in patients with composite lymphedema (p = 0.012). The combined treatment with radiotherapy was related to submandibular external lymphedema (p = 0.009), altered pharyngolaryngeal sensitivity (0.040), presence of residue (p = 0.001) and penetration to pasty (p = 0.007) and internal edema in almost all structures. There was also a higher percentage of residue in cases with internal altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor of edema. Cervicofacial and pharyngolaryngeal lymphedema is a frequent event after treatment for HNC, with important impact on swallowing performance characterised by altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor.
Background
Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis of Parkinson’s disease (PD), thus, it is reliable to promote the clearance of α-synuclein to prevent and treat PD. Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules, however, their pathophysiological aspects remain elusive.
Method
Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes. Six weeks later, glymphatic functions and PD-like phenotypes were systemically analyzed.
Results
Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice, accompanied with perivascular aggregation of α-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra. Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice, causing more severe accumulation of α-synuclein, glial activation, inflammation, dopaminergic neuronal loss and motor deficits.
Conclusion
The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.
Electronic supplementary material
The online version of this article (10.1186/s40035-019-0147-y) contains supplementary material, which is available to authorized users.
Background:. Identification and localization of functional lymphatic vessels are important for lymphaticovenular anastomosis. Conventional high-frequency ultrasound (CHFUS) has been reported to be useful for them, but it has some disadvantages. In this article, we present new capabilities of ultra high-frequency ultrasound (UHFUS) for imaging of the lymphatic vessels, which may overcome the weakness of CHFUS.
Methods:. Thirty unaffected extremities in 30 unilateral secondary lymphedema patients (13 upper limbs and 17 lower limbs) were examined. Identification of the lymphatic vessels using UHFUS and CHFUS were performed at 3 sites in each unaffected extremity. Number and diameter of the detected lymphatic vessels were compared between UHFUS and CHFUS groups. At the same time, new characteristics of the lymphatic vessels seen with UHFUS were investigated.
Results:. One hundred sixty-nine lymphatic vessels were detected with UHFUS, and 118 lymphatic vessels with CHFUS. The number of lymphatic vessels found in upper and lower extremities was significantly larger with UHFUS than with CHFUS. The diameter of lymphatic vessels found in upper and lower extremities was significantly smaller with UHFUS than with CHFUS. All lymphatic vessels that were detected in UFHUS were less likely to collapse when the transducer was against the skin of the examined sites.
Conclusions:. Detection rate of the lymphatic vessels in nonlymphedematous extremities with UHFUS was higher than that with CHFUS. UHFUS provides images with extremely high resolution, demonstrating new characteristics of the lymphatic vessels.
Ten head and neck cancer survivors diagnosed with head and neck lymphedema (HNL) were imaged using near-infrared fluorescence lymphatic imaging (NIRFLI) prior to and immediately after an initial advance pneumatic compression device treatment and again after 2 weeks of daily at-home 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. © American Academy of Otolaryngology–Head and Neck Surgery Foundation 2019.
Background:
Patients who have undergone treatment for head and neck cancer are at risk for neck lymphedema, which can severely affect quality of life. Liposuction has been used successfully in cancer patients who suffer from post-treatment limb lymphedema. The purpose of our study was to review the outcomes of head and neck cancer patients at our center who have undergone submental liposuction for post-treatment lymphedema and compare their subsequent results with a control group.
Methods:
All head and neck cancer patients at an oncology center in tertiary hospital setting who complained to their attending surgeon or radiation oncologist regarding cervical lymphedema secondary to head and neck cancer treatment, and had been disease-free for a minimum of one year, with no previous facial plastic surgical procedures were eligible for inclusion into the study. Study design was a non-blinded randomized controlled trial. Twenty patients were randomized into a treatment arm (underwent submental liposuction n = 10) and control arm (n = 10). Both groups of patients completed two surveys (Modified Blepharoplasty Outcome Evaluation and the validated Derriford Appearance Scale) on initial office visit after consenting for the trial. The treatment group then completed the surveys 6 months post-operatively while the control group filled the surveys 6 months after the initial assessment but had no intervention. Mann-Whitney U tests were performed to compare the responses of those that did and did not receive liposuction.
Results:
Our study demonstrated a statistically significant improvement in patients' self-perception of appearance and statistically significant subjective scoring of appearance following submental liposuction.
Conclusions:
Submental liposuction is an effective and safe procedure to improves the quality of life for head and neck cancer patients suffering from post-treatment lymphedema.
Background:
This functional usability study assessed ease of use, fit, comfort, and potential clinical benefits of advanced pneumatic compression treatment of cancer-related head and neck lymphedema.
Methods:
Patient-reported comfort and other treatment aspects were evaluated and multiple face and neck measurements were obtained on 44 patients with head and neck lymphedema before and after 1 treatment session to assess usability and treatment-related lymphedema changes.
Results:
A majority of the patients (82%) reported the treatment was comfortable; most patients (61%) reported feeling better after treatment, and 93% reported that they would be likely to use this therapy at home. One treatment produced overall small but highly statistically significant reductions in composite metrics (mean ± SD) of the face (82.5 ± 4.3 cm vs 80.9 ± 4.1 cm; P < .001) and neck (120.4 ± 12.2 cm vs 119.2 ± 12.1 cm; P < .001) with no adverse events.
Conclusion:
Results found the treatment to be safe, easy to use, and well tolerated while demonstrating edema reduction after a single initial treatment.
Background:
Tumor/treatment-related internal lymphedema (IL) and/or external lymphedema (EL) are associated with functional deficits and increased symptom burden in head and neck cancer patients (HNCP). Previously, we noted association between EL/IL and patient-reported dysphagia using the Vanderbilt Head and Neck Symptom Survey (VHNSS) version 1.0.
Objective:
To determine the relationship between IL/EL and subjective and objective measures of swallowing function.
Methods:
Eighty-one HNCP completed: (1) VHNSS version 2.0, including 13 swallowing/nutrition-related questions grouped into three clusters: swallow solids (ss), swallow liquids (sl), and nutrition(nt); (2) physical assessment of EL using Foldi scale; (3) endoscopic assessment of IL using Patterson scale (n = 56); and (4) modified barium swallow study rated by dysphagia outcome and severity scale (DOSS) and in conjunction with a swallow evaluation by National Outcomes Measurement System (NOMS). Examinations were performed at varied time points to assess lymphedema spectrum, from baseline (n = 15, 18.1%) to 18 months post-therapy (n = 20, 24.1%).
Results:
VHNSS swallow/nutrition items scores correlated with NOMS/DOSS ratings (p < 0.001). Highest correlation was with NOMS: ss (-0.73); sl (-0.61); nt (-0.56). VHNSS swallow/nutrition scores correlated with maximum grade of swelling for any single structure on Patterson scale: ss (0.43; p = 0.001); sl (0.38; p = 0.004); nt (0.41; p = 0.002). IL of aryepiglottic/pharyngoepiglottic folds, epiglottis, and pyriform sinus were most strongly correlated with VHNSS and NOMS ratings. NOMS/DOSS ratings correlated with EL (> = -0.34; p < 0.01). No meaningful correlations exist between VHNSS swallow/nutrition items and EL (< ± 0.15, p > 0.20).
Conclusions:
IL correlated with subjective and objective measures of swallow dysfunction. Longitudinal analysis of trajectory and impact of IL/EL on dysphagia is ongoing.
The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.
© 2015 Aspelund et al.
Head and neck lymphedema (HNL) is an increasingly recognized complication of head and neck cancer and its treatment. However, no consensus exists on the “gold‐standard” assessment tool for the purposes of diagnosis, classification, or monitoring of HNL. We conducted a systematic review of the literature regarding HNL assessment to determine the optimal method/s of assessment for patients with HNL. A review of publications between January 2000 and September 2021 was undertaken on four electronic databases. Studies were excluded if no clear assessment method of HNL was documented. Sixty‐seven articles were included in the study. A wide range of assessment methods for HNL have been reported in the literature. For the purposes of diagnosis and classification of physical findings, computed tomography (CT) appears the most promising tool available for both external and internal HNL. In terms of monitoring, ultrasound appears optimal for external HNL, while a clinician‐reported rating scale on laryngoscopy is the gold standard for internal HNL. Patient‐reported assessment must be considered alongside objective methods to classify symptom burden and monitor improvement with treatment.
Purpose: Head and neck lymphedema is a common condition following head and neck cancer (HNC) treatment, with substantial functional morbidity. This systematic review aimed to (1) identify tools used to assess head and neck lymphedema in HNC patients and (2) determine their validity and reliability. Methods: Electronic and hand searches of Prospero, MEDLINE, Cochrane Library, and Embase were searched from their inception until April 2021, and hand searches were independently screened by two reviewers. Studies were included if they were available in English and measured lymphedema in adult HNC patients (aged ≥18 years). Data including psychometric characteristics were extracted and synthesized narratively, with the Quality Assessment of Diagnostic Accuracy Studies-2 and the COnsensus-based Standards for the selection of health Measurement INstruments checklists used to assess risk of bias. Results: Thirty-three studies, reporting 38 assessment tools, were included. Assessments included clinician rating scales, symptom inventories, size measures, measures of internal edema, radiographic and ultrasonographic measures, and quality-of-life measures. Of the 38 measures cited, only 11 had any degree of validation and reliability testing. Risk of bias varied among the different assessment tools. Conclusion: While many tools are used in the assessment of head and neck lymphedema, the majority of these tools lack validation and reliability data. Only one tool, the Head and Neck Lymphedema and Fibrosis Symptom Inventory, met criteria for strong quality assessment. Further efforts to establish a core set of metrics for this complex condition are warranted.
Background: Lack of reliable and valid tools significantly impacts early identification and timely treatment of lymphedema and fibrosis (LEF) in the head and neck cancer population. To address this need, we developed and reported a patient-reported outcome measure (Head and Neck Lymphedema and Fibrosis Symptom Inventory [HN-LEF SI]). This article reports the construct validity (convergent and divergent validity) testing of the tool. Materials and Methods: A prospective, longitudinal, instrument validation study was conducted in patients with a newly diagnosed oral cavity or oropharyngeal cancer. Participants completed the HN-LEF SI and six carefully selected self-report measures at pretreatment, end-of-treatment, and every 3 months up to 12 months after treatment. Spearman correlations were used. Results: A total of 117 patients completed the study. Patterns of correlations of the HN-LEF SI scores with the established self-report measure scores were consistent with expected convergent and divergent validity. Conclusion: Evidence from this work supports the construct validity of the HN-LEF SI.
Objective:
The Patterson Edema scale was developed in 2007 to address the lack of a reliable, sensitive scale to measure laryngeal and pharyngeal edema in patients with head and neck cancer. The objective of this study was to revise the existing Patterson scale to improve its reliability and utility.
Design:
Prospective investigation SETTING: Academic medical center PARTICIPANTS: Speech-Language Pathologists, Otolaryngologists, and Radiation Oncologists MAIN OUTCOME MEASURES: Ratings using the Revised Patterson Edema Scale METHODS: A consensus group reviewed existing literature regarding the performance of the original Patterson scale and revised the existing scale in regard to items to be included and descriptors for each severity level. The scale was then utilized by 18 speech language pathologists from the US and UK with >2 years-experience working with dysphagia and dysphonia with endoscopy. Each SLP rated a total of eight parameters (epiglottis, vallecula, pharyngoepiglottic folds, aryepiglottic folds, arytenoids, false vocal folds, true vocal folds, and pyriform sinuses) using the Revised Patterson Edema Scale. Feedback was solicited from raters regarding areas where clarity was lacking for further scale revision. Scale revisions were completed and additional ratings were completed by otolaryngologists, radiation oncologists, and less experienced SLP providers to establish reliability across disciplines. Quadratic weighted Kappa values were obtained to establish interrater reliability.
Results:
Feedback received from raters included suggestions for clarification of how to rate unilateral edema, use of a standard task battery to visualize and rate structures consistently, and clarification of true vocal fold edema rating parameters. Overall interrater reliability was established using quadratic weighted Kappa with good agreement noted for the epiglottis, vallecula, arytenoids, and false vocal folds; moderate agreement noted for aryepiglottic folds, pharyngoepiglottic folds and pyriform sinuses; and fair agreement noted for true vocal folds.
Conclusions:
The Revised Patterson Edema Scale demonstrates moderate-substantial interrater reliability for most parameters across multiple disciplines and experience levels, with the exception of the true vocal folds where agreement was fair. We believe the Revised Patterson Edema Scale provides a reliable tool for clinicians and researchers to rate edema in the supraglottic larynx and pharynx following treatment for head and neck cancer.
The microsurgical options for lower limb lymphedema is challenging. In search to improve the overall result, we hypothesized it would be beneficial to add functioning lymph node to vein anastomosis (LNVA) in addition to lymphovenous anastomosis (LVA).
This is a retrospective study of 160 unilateral stage II & III lower extremity lymphedema comparing the outcome between LNVA + LVA group and LVA only group from May 2013 to June 2018. MRI was used to identify functioning lymph nodes. Patient outcome including lower extremity circumference, body weight, bio impedance test and other data were analyzed to evaluate whether LNVA improved outcome.
The LNVA + LVA group showed significantly better results for circumference reduction rate, body weight reduction rate and extracellular fluid reduction rate of the affected limb compared to the LVA only group for both stage II and III. The MRI imaging revealed 9 cases had no identifiable lymph nodes of the affected limb and 54 cases with nonfunctioning lymph node upon exploration despite positive imaging. Correlation showed lymph node size needed to be least 8 mm in the MRI to be functional.
The LNVA + LVA approach for lymphedema has benefit of having better reduction compared to LVA alone in the lower limb as well as the suprapubic region. Preoperative MRI will help to identify functioning lymph node increasing the overall probability of positive outcome.
An intimate knowledge of the lymphatic drainage of the head and neck is needed by the clinician examining and diagnosing patients with lesion of this region.
It is considered that approximately 150 to 300 lymph nodes are located in the neck region. The classification of cervical lymph nodes by Rouvière has long been most widely referenced in textbooks and articles because it covers most of the lymph nodes of the head and neck region. Anatomical review of the lymphatic system of the head and neck helps surgeons understand and treat the patients who have any cancers and cancer metastasis in and around the head and neck regions. Regardless, comprehensive review of the lymphatic system of the head and neck has been rarely discussed. This paper details the anatomy of the lymphatics of these regions by reviewing related publications, books, official reports from the academic society and also describes the clinical manifestations and levels used in staging of the various lymph nodes with illustrations and computed tomographic images.
Background
This study aimed to examine the prevalence, location, and severity of chronic internal, external, and combined head and neck lymphedema (HNL) in patients with head and neck (HNC) who were treated with definitive chemoradiotherapy (CRT) or postoperative radiotherapy (PORT).
Methods
Sixty‐two participants between 1 and 3 years post‐treatment were recruited. Internal HNL was rated with Patterson's Scale. External HNL was graded with the MD Anderson Cancer Center Lymphedema Rating Scale.
Results
Ninety‐eight percent of participants presented with some form of chronic HNL. Sixty‐one percent had internal HNL only, 35% had combined HNL, and 2% had external HNL only. Participants treated with PORT were more likely to experience combined HNL (69% vs 24%, P = .001), whereas those treated with CRT were more likely to have internal HNL only (74% vs 25%, P = .001).
Conclusions
Chronic HNL is highly prevalent following multimodal treatment, and differences in HNL presentations exist between treatment modalities.
Objective:
This study aimed to compare outcomes in patients with head and neck lymphedema receiving either a home-based lymphedema treatment program or a hybrid approach including both home-based treatment and regular clinical visits.
Methods:
Outcomes were assessed in patients receiving head and neck lymphedema rehabilitation. Baseline measures of neck, submental, and facial edema were obtained and repeated following treatment. A home program was recommended for all patients, and those receiving hybrid care received the same recommendations as well as a visit with the lymphedema therapist for additional treatment. Their outcomes were compared using standard statistical analysis.
Results:
Fifty consecutive individuals were included, 25 in each group. Adherence to at least 50% of recommended treatment was reported in 68% of those receiving home-based treatment and 84% of those receiving hybrid care. Significant improvement was demonstrated for 66% of patients. There was no statistically significant difference between treatment groups with regard to clinically significant improvement (P = .15). Patients receiving hybrid therapy demonstrated treatment advantages regarding facial edema (P = .037). Adherence to treatment was associated with clinical improvement (P = .047).
Conclusions:
Comparable benefits were observed regardless of whether patients had a home-based or hybrid lymphedema treatment approach. These data suggest a home-based treatment approach may be appropriate for patients unable to participate in clinical sessions. However, for patients with significant facial edema, a hybrid approach may be preferable. Adherence was associated with better outcomes. Given these findings, future investigations should consider strategies to improve adherence to optimize the outcomes lymphedema treatment.
Level of evidence:
3b Laryngoscope, 2020.
Background:
Sometimes, injecting indocyanine green (ICG) or isotope at distal limbs is insufficient especially in cases with low lymphatic function. The purpose of this study was to elucidate the usefulness of multi-lymphosome injection ICG lymphography.
Methods:
Two hundred and six lower limbs of 103 patients were included. ICG lymphography was performed by injecting ICG in three lymphosomes per limb: dorsum of foot (saphenous lymphatics), the proximal side of the lateral condyle (lateral calf lymphatics), and the lateral side of the superior edge of the knee (lateral thigh lymphatics). We observed the presence or absence of a linear pattern at each injection site with a near-infrared camera. Lymphoscintigraphy was performed by injecting an isotope in the first web space, conventionally. Whole body scintigrams were taken 60 min after injection.
Results:
In multi-lymphosome ICG lymphography, the lateral thigh lymphatics were observed as a linear pattern in 75.2% of patients, the lateral calf lymphatics in 72.8%, and the saphenous lymphatics in 84.5% of patients. There was not a significant difference between secondary and primary lymphedema (p = 0.57, 0.77, and 0.56 in the lateral thigh, the lateral calf, and the saphenous lymphatics, respectively). Among the 12 limbs classified as Type 5, at least one linear pattern was found in 10 limbs (83.3%).
Conclusions:
We observed a linear pattern in 83.3% of the limbs that were lymphoscintigraphic Type 5 by using multi-lymphosome ICG lymphography. There is a possibility that the results of this study can increase the number of patients eligible for lymphatico-venous anastomosis (LVA) and increase the success rate of LVA.
Background Extremity lymphedema is a dreaded complication of ilioinguinal or axillary lymphadenectomy. In conventional lymph node dissection, no effort is performed to maintain or reestablish extremity lymphatic circulation. We hypothesized that immediate lymphatic reconstruction (ILR) could be a reproducible procedure to maintain functional lymphatic flow after ilioinguinal and axillary lymphadenectomy in patients with malignant melanoma. This is the first report describing prophylactic ILR in patients with melanoma who underwent complete lymph node dissection for gross nodal disease.
Methods We report a case series of 22 malignant melanoma patients who had axillary or ilioinguinal lymph node dissection for bulky locoregional invasion with immediate lymphatic reconstruction. A novel method to identify and select lymphatics with high flow using fluorescent lymphangiogram with indocyanine green dye gradient software is described. Surgical details, common difficulties, as well as indications are discussed. Instructional videos are also provided.
Results Our technique is reproducible, since we have successfully completed immediate lymphatic reconstruction in 22 cases consecutively. Intradermal indocyanine green injections allowed for visualization of 1 to 3 transected lymphatics after lymphadenectomy. An average of 1.8 lymphaticovenous bypass (range 1–3) was performed per patient.
Conclusion Reestablishment of lymphatic circulation after ilioinguinal or axillary lymphadenectomy in patients with melanoma characterizes a novel method that may reduce the problem of upper and lower extremity iatrogenic lymphedema. This is particularly important given the emergence of new adjuvant treatment modalities that considerably improve patients' survival after lymphadenectomy.
Objective:
To perform the first systematic review evaluating all established treatment modalities of head and neck lymphedema resulting from head and neck cancer therapy. Since craniofacial lymphedema treatment represents unique challenges not addressed by extremity lymphedema therapies, a systematic review and evaluation of treatment modalities specific to this area is needed to guide clinical management and further research.
Data sources:
Four electronic databases were searches from inception to September 2018. These included Scopus (Embase), PubMed (Medline), Clinicaltrials.gov, and Cochrane Databases.
Review methods:
A search string was developed, and all databases queried for keywords on three subjects: head and neck cancer, lymphedema, and therapy. Results were uploaded to an EndNote database where relevant items were identified by hand-searching all titles and abstracts. Subsequently results were combined, duplicates removed, and full papers screened according to eligibility criteria.
Results:
Of a total 492 search results, twenty-six items met eligibility criteria for this review. These included fourteen cohort studies, seven case reports, two randomized controlled trials, two systematic reviews, and one narrative review totaling 1018 study subjects. The manual lymph drainage group had the largest number of studies and participants, with fewer studies investigating selenium, liposuction, and lymphaticovenular anastomosis.
Conclusion:
Evidence for the efficacy of all types of lymphedema therapy is limited by paucity of large randomized controlled trials. While manual lymph drainage is best studied, liposuction and surgical treatments have also been effective in a small number of patients.
Recent advancements in microsurgery and supermicrosurgery have made effective lymphedema treatment a surgical reality. When comparing the 2 currently available procedures, lymphaticovenular anastomosis (LVA) and vascularized lymph node transfer, vascularized lymph node transfer is more frequently performed owing to technical unfamiliarity with supermicrosurgery and uncertainty in patient selection, technical execution, and procedural outcome. To date, the author has performed more than 250 cases of supermicrosurgical LVAs. In this article, the author shares his approach in technical acquisition, how to get over the learning curve using a simulation model, patient selection, LVA-specific technical pearls, outcome assessment, and finally how to team up with other lymphedema-related specialists. After reading this paper, the readers should have enough knowledge to get started building a surgical lymphedema program.
Background
Facial edema is a common complication after neck dissection and/or chemoradiotherapy for head and neck cancer. Edema subsides spontaneously in most cases but sometimes persists, in which case surgical intervention is required. We report a case of severe facial edema that showed significant improvement upon lymphovenous anastomosis (LVA).
Methods
A 66‐year‐old man with oral floor cancer developed progressive facial lymphedema after tumor resection, bilateral neck dissections, chemoradiotherapy, and fibular and rectus abdominis musculocutaneous flap transfer. His eyesight was completely disturbed due to severe eyelid edema. The LVAs were performed in the bilateral preauricular area. Surgical findings showed stagnation of the lymphatic fluids in dilated lymphatic vessels, which were drained to the superficial temporal veins by LVA.
Results
The edema subsided rapidly and the patient's eyesight returned as soon as 4 days postoperatively.
Conclusion
Using LVA in the preauricular region can be a choice of surgical treatment for severe facial edema.
Background:
The superficial (subcutaneous) facial fat compartments contribute to the signs of facial aging, but a comprehensive anatomic description of their location and their functional behavior during the application of soft tissue fillers still remains elusive.
Methods:
We investigated 30 fresh frozen cephalic specimens from 13 male and 17 female Caucasian body donors (age: 78.3 ± 14.2 years, body mass index: 23.1 ± 5.3 kg/m). Upright positioned contrast enhanced CT scans and additional MR imaging was performed. 3D reconstruction based measures were conducted to evaluate the position of the applied contrast agent in each compartment separately. Successive anatomical dissections were performed to confirm the imaging findings.
Results:
Positive correlations were detected between the amounts of injected material and the inferior displacement for the superficial nasolabial (rp = 0.92, p = 0.003), middle cheek (rp = 0.70, p = 0.05) and jowl (rp = 0.92, p = 0.03) compartments but not for the medial cheek (rp = 0.20, p = 0.75), lateral cheek (rp = 0.15, p = 0.75), the superior superficial temporal compartments superior: rp = -0.32, p = 0.41; or the inferior superficial temporal compartment: rp = -0.52, p = 0.29.
Conclusion:
This study confirms the presence of distinct subcutaneous fat compartments and provides evidence for an individual behavior when soft tissue fillers are applied: inferior displacement of the superficial nasolabial, middle cheek and jowl compartments, in contrast to an increase in volume without displacement, i.e. an increase in projection of the medial cheek, lateral cheek and both superficial temporal compartments.
Advances in our understanding of the lymphatic system and the pathogenesis of lymphedema have resulted in the development of effective surgical treatments. Vascularized lymph node transfer (VLNT) involves the microvascular transplantation of functional lymph nodes into an extremity to restore physiological lymphatic function. It is most commonly performed by transferring combined deep inferior epigastric artery perforator and superficial inguinal lymph node flaps for postmastectomy breast reconstruction. For patients who do not require or are unable to undergo free abdominal breast reconstruction or have lymphedema affecting the lower extremity, several other VLNT options are available. These include flaps harvested from within the axillary, inguinal, or cervical lymph node basins, and lymph node flaps from within the abdominal cavity. This article reviews the lymph node flap options and techniques available for VLNT for lymphedema.
Objectives
Recently, it has been confirmed, that excess fluid and waste products from the brain are drained into the cerebrospinal fluid (CSF) and afterwards cleared via the olfactory route and/or lymphatic vessels in the brain dura and corresponding extracranial lymphatic structures. Therefore, the aim of present study was to monitor time-dependent uptake of Evans blue (EB) tracer from subarachnoid space into the meningeal lymphatic vessels and extracranial lymph nodes in rats during 3 hours–12 days.
Methods
EB was injected into the cisterna magna of anesthetized rats and after required survival, plasma, brain dura matter and corresponding lymph nodes (cervical, thoracic and lumbar) were dissected and processed for lymphatic vessels analyses using immunofluorescence and immunohistochemistry. Furthermore, we have used sensitive ultra-high-performance liquid chromatography (UHPLC) method for the determination of EB concentrations in selected samples.
Results
Using a combination of imaging methods, we have detected two different types of the vascular structures in the brain dura and in deep cervical lymph nodes. The blood vessels, which were RECA-1 + positive and the lymphatic-like vessels, expressing bright intense red fluorescence of EB tracer. Subsequently, using UHPLC with UV detection, we have quantified the EB concentration in positive structures by 3 hours up to 12 days after tracer delivery. A significant increase of EB concentration was detected in deep cervical lymph nodes already at 3 hours with a peak at 1 day that decreased to about one-tenth of its peak value by 12 days. Similar pattern was detected in brain dura. On the contrary, the brain tissue and plasma were almost negative for EB tracer during all tested time periods.
Conclusion
Our results demonstrate the dynamic changes of EB in meningeal lymphatic vessels and in deep cervical lymph nodes, thus recapitulating the downstream outflow of intracisternally injected tracer during 3 hours–12 days via dura mater lymphatic vessels towards corresponding extracranial draining system, particularly the deep cervical lymph nodes.
Background:
The purpose of this pilot study was to examine a therapeutic intervention for head and neck lymphedema. The 22-week intervention involved therapist-led care and participant self-management. Effectiveness was evaluated using a previously described lymphedema assessment tool, the Assessment of Lymphedema of the Head and Neck (ALOHA) to detect change over the course of the 22 weeks of treatment, and before and after a single treatment session.
Methods:
A prospective observational pilot study was conducted with a cohort of 10 participants assessed. Measurements of size (tape measurements) and water content (tissue dielectric constant [TDC]) were used, per the ALOHA protocol. Participants received 13 lymphedema therapy treatments at reducing frequencies over 22 weeks and daily self-management.
Results:
There was an overall significant reduction in lower neck circumference (F [2.15,19.35] = 7.11; P = .004), upper neck circumference (F [5,45] = 7.27; P < .001) and TDC (F (5,45) = 8.92; P < .001) over time. There were no significant differences over the course of treatment for mean ear-to-ear measurements or before and after a single session of treatment.
Conclusion:
This pilot study found a reduction in head and neck lymphedema over the 22-week lymphedema treatment course. This intervention may be successful in reducing head and neck lymphedema; however, further studies are needed to investigate these findings in a larger sample with the use of a control group to negate improvements from healing over time.
Background Microsurgical vascularized lymph node transfer (VLNT) and supermicrosurgical lymphaticovenular anastomosis (LVA) are increasingly performed to treat lymphedema. The surgical outcome is commonly assessed by volume-based measurement (VBM), a method that is not consistently reliable. We describe indocyanine green (ICG) lymphography as an alternative postoperative tracking modality after lymphatic reconstruction with VLNT and LVA. Methods VLNT and LVA were performed in patients with therapy-refractory lymphedema. Patients were evaluated qualitatively by clinical assessment, quantitatively with VBM, and lymphographically using ICG lymphography. The evaluation was performed preoperatively, and at 3, 6, and 12-month postoperatively. Results Overall, 21 patients underwent lymphatic reconstruction with either VLNT or LVA. All reported prompt and durable relief of symptoms during the study period. All experienced disease regression based on the Campisi criteria. Out of the 21 patients, 20 (95%) demonstrated lymphographic down staging of disease severity. Out of the 21 patients, 3 (14%) developed a paradoxical increase in limb volume based on VBM despite clinical improvement. Conclusions ICG lymphography correlated highly with patient self-assessment and clinical examination, and is an effective postoperative tracking modality after lymphatic reconstruction.
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Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.
Background and Methods
Indocyanine green (ICG) lymphography is one of several methods of lymphography to detect lymphatic channels and evaluate patients clinically with limb lymphedema. ICG imaging is made possible by the use of a near-infrared camera device. The fluorescence images were digitalized for real-time display. ResultsICG lymphography findings are largely classifiable into two patterns: normal linear pattern and abnormal dermal backflow (DB) pattern. ICG lymphography pattern changes from the normal linear pattern to abnormal DB patterns in obstructive peripheral lymphedema; with progression of lymphedema, DB patterns change from splash pattern, to stardust pattern, and finally to diffuse pattern. We classify ICG lymphography progression into 0 to V stages for the upper extremity, the lower extremity and into 0 to IV stages for the genital area. Conclusion
In DB stage II, most patients are symptomatic; thus, aggressive treatments, such as lymphaticovenular anastomosis, are indicated. In DB stages III to V, lymphaticovenular anastomosis is recommended because most patients are refractory to conservative therapies.
Currently, assessment and measurement of lymphedema in head and neck cancer patients is difficult. The aims of this report are to examine the current state of science regarding available measurement of head and neck lymphedema, to identify gaps in clinical evaluation of head and neck lymphedema, and to propose future research directions for advancing the assessment of head and neck lymphedema. The authors conducted a comprehensive literature review based on PubMed, CINAHL, Cochrane database, EMBASE, and PsycINFO from 1989 to 2014. Primary search terms included head and/or neck cancer, head and/or neck and/or face, lymphedema, edema, swelling, fibrosis, measurement, assessment, and evaluation. The authors also reviewed information from the Oncology Nursing Society, National Lymphedema Network, National Cancer Institute, American Cancer Society, and other related healthcare professional association web sites. Based on the nature/characteristics of measurement reported in the literature, methods for assessment of head and neck lymphedema can be categorized into: (1) patient-reported outcome (PRO) measures (e.g., symptom tool), (2) clinician-reported outcome (CRO) measures based on clinical grading criteria via a clinical exam (external lymphedema evaluation by physical examination and internal edema examination via endoscopy), and (3) technical capacity/measurement techniques (e.g., imaging techniques). Although a number of measures have been reported in the literature, clinically useful PRO and CRO measures, and reliable and sensitive measurement techniques need to be validated to address gaps in assessment of head and neck lymphedema, and to be easily used in early identification of lymphedema and assessment of treatment/interventional effects.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Background:
There is no clinical assessment available to measure head and neck lymphedema. This study proposes the use of a tape measurement system and the MoistureMeterD (MMD) to evaluate head and neck lymphedema.
Methods:
The reliability and validity of these assessments was examined in 20 patients with head and neck lymphedema and 20 matched healthy controls.
Results:
Interrater reliability for the MMD and 3 of the 4 tape measurements was excellent (intraclass correlation coefficients [ICCs] >0.90). Intrarater reliability of the MMD was 0.97. The MMD discriminated between patients with head and neck lymphedema and healthy controls, t(19) = 8.97, p < .001, whereas the tape measurements did not. Correlation between MMD score and head and neck lymphedema level ratings was significant (rho = 0.59) indicating convergent validity. Three of the tape measurements were significantly correlated with MMD scores (rho = 0.37-0.38) but not with ratings of head and neck lymphedema.
Conclusion:
The tape measurement system and MMD show potential as objective measurements of head and neck lymphedema with the exception of 1 tape measurement point. © 2014 Wiley Periodicals, Inc. Head Neck, 2015.