Vaughan Keeley

A new classification system for primary lymphatic dysplasias based on phenotype.

Connell F, Brice G, Jeffery S, Keeley V, Mortimer P, Mansour S. A new classification system for primary lymphatic dysplasias based on phenotype.

The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review

Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000–1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function.

The Prevalence of Nocturnal Hypoxemia in Advanced Cancer

Nocturnal hypoxemia is associated with excessive daytime sleepiness in patients with chronic respiratory disease. This relationship has not been explored in patients with cancer. This study examined the prevalence of nocturnal hypoxemia in patients admitted to a specialist palliative care unit, and explored relationships with demographic and physiological parameters, opioid or other sedative drug use, and daytime sleepiness, fatigue, and quality of life. Demographic details, diagnosis, performance status, body mass index, opioid or other sedative drug use, hemoglobin, spirometry, and sniff nasal inspiratory pressures were obtained, along with Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, and Short Form-36 health questionnaire scores. An oximeter recorded resting daytime oxygen saturation (SaO2); overnight SaO2 was recorded for a minimum of five hours. Nocturnal hypoxemia was defined as SaO2<90% for >or=2% of the monitored nighttime. Of 100 patients, 35 had nocturnal hypoxemia. These were more likely to have lung disease (P<0.05), a lower forced expiratory volume in one second % predicted (P=0.01), lower daytime SaO2 (P=0.01) and higher levels of mental fatigue (difficulty concentrating) (P=0.02), compared to those without nocturnal hypoxemia. Both groups exhibited abnormal levels of daytime sleepiness. Nocturnal hypoxemia is common in this group of patients and may contribute to mental fatigue (difficulty concentrating).

Abstract PD4-02: A study to determine the optimal method of detection and threshold for lymphoedema intervention: a multi-centre prospective study

Introduction Lymphoedema, a complication of nodal surgery in 30-40% of patients, reduces quality of life for sufferers. This prospective, multi-centre study compared multi-frequency bioimpedance spectroscopy (BIS, ImpediMed) with a validated perometer method to determine which test is more sensitive for detecting lymphoedema after axillary clearance and identify the factors predicting lymphoedema development. Material and methods Participants (n = 629) undergoing axillary clearance at 9 UK centres underwent pre-operative and arm volume measurements post-surgery (1, 3, 6, 9 & 12 months, then 6 monthly) by arm perometry, BIS measurements (L-Dex) and recorded self-reported symptoms via questionnaires. Follow-up was a minimum of two years from surgery. Change in arm volume was calculated using relative arm volume change (RAVC) with >10% increase defined as lymphoedema. The predictors of lymphoedema development and optimal method for its detection were assessed using Cox Regression, Log Rank and Kaplan-Meier survival analyses. Results In total, 629 women underwent axillary surgery, with a median age of 56 (range 22 to 90) years; 80% were ER positive and received endocrine therapy, 78% received radiotherapy and 65% received chemotherapy. Lymphoedema was detected by 24 months in 124 (20%) women by perometry. Using the LDex >10 cut-off score, bioimpedance sensitivity was 71% and specificity was 89% (PPV 47%) compared to RAVC changes. Women who had an RAVC >5%- 0.000001). Twenty-six per cent of ER negative patients developed lymphoedema compared to 19% ER positive cancer patients. The type (taxane versus no taxane) and whether chemotherapy was neo-adjuvant or adjuvant did not predict lymphoedema development. Univariate analysis revealed BMI (p=0.003), ER negativity (p= 5%- 5%- Conclusions This is the first report; ER negative cancer is associated with an increased risk of lymphoedema after axillary node clearance. Arm measurements should be taken from baseline in all patients undergoing axillary surgery and increases greater than 3% should lead to further surveillance to prevent lymphoedema development. Perometer measurement is the optimal technique for measuring and predicting the development of lymphoedema. A threshold RAVC of >5%- (Funded by NIHR Programme Grant). Citation Format: Bundred NJ, Ashton S, Riches K, Ashcroft L, Evans A, Todd C, Bramley M, Hodgkiss T, Purushotham A, Keeley V. A study to determine the optimal method of detection and threshold for lymphoedema intervention: A multi-centre prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD4-02.

Abstract P6-08-07: Optimal method of detection and threshold for early intervention to prevent lymphoedema: A multi-centre prospective study

Introduction Women who undergo axillary surgery are at risk of developing lymphoedema. Early detection is recommended by measuring arm volume from a baseline before surgery to enable early intervention. The optimal measurement method to enable early detection and time to intervention are unclear. This prospective multi-centre study compares multi-frequency bioimpedance spectroscopy (BIS, ImpediMed) with the validated perometer method to determine which test is more sensitive for detecting the optimal threshold to prevent lymphoedema. Methods Participants (N = 960) undergoing axillary clearance at 9 UK centres have pre-operative and regular arm volume measurements post-surgery (1, 3, 6, 9 & 12 months, then 6 monthly), by the validated arm perometry compared with BIS (L-Dex) measurements as well as self-reported symptoms questionnaire. Change in arm volume was calculated using relative arm volume change (RAVC). The predictors of lymphoedema development and optimal method were assessed. Results Currently 612 patients, median age 55 (range 24 to 90) years, have 6 month follow-up data and 327 have 18 month follow-up data. Seventy six percent were ER positive and received endocrine therapy, 84% percent received radiotherapy and 67% received chemotherapy in addition to surgery. Lymphoedema by 18 months was detected in 19% (n=79) of women by perometry (≥10% RAVC) and a change in L-Dex of 10 was observed in 31% of women. A moderate correlation between perometer and BIS at 3 months (r=0.40) and 6 months (r=0.60), with a sensitivity of 73% and specificity of 84% was found. Univariate analysis revealed a threshold for early intervention to prevent lymphoedema was RAVC ≥5%- Conclusions The optimal threshold for early intervention to prevent progression to lymphoedema is ≥5%- (Funded by NIHR Programme Grant). Citation Format: Nigel J Bundred, Charlotte Stockton, Katie Riches, Linda Ashcroft, Abigail Evans, Anthony Skene, Maria Bramley, Tracey Hodgkiss, Arnie Purushotham, Vaughan Keeley, BEA Investigators. Optimal method of detection and threshold for early intervention to prevent lymphoedema: A multi-centre prospective study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-07.

Abstract P3-09-09: Comparison of multi-frequency bioimpedance with perometry for the early detection of lymphoedema after axillary node clearance

Introduction Women who undergo axillary clearance are at risk of developing lymphoedema. Early detection is recommended by arm volume measurements from a baseline before surgery but the optimal test is unclear. This prospective multi-centre study compares multi-frequency bioimpedance spectroscopy (BIS, ImpediMed) with the validated perometer method to determine which test is more sensitive for detecting lymphoedema within 24 months of surgery. Results from 441 women with up to six months follow-up are reported here to determine whether the timing of arm measurement affects results. Methods Participants (N = 441) undergoing Axillary Clearance underwent pre-operative and subsequent regular measurements post-surgery (1, 3, 6, 9 & 12 months, then 6 monthly), of arm volume by perometry and BIS measurements as well as self-reported symptoms of swelling, numbness or heaviness. The primary endpoint of lymphoedema was defined as ≥10% increase in volume compared to the contralateral arm by perometry. Results We report the data from 441 patients with 6 month follow-up data, their median age is 55 years ranging from 27 to 90 years. Eighty percent of patients were ER positive and received endocrine therapy as well as surgery. Eighty percent also underwent radiotherapy to the breast or chest wall, while 70% received chemotherapy in addition to surgery. Mean percentage increase in arm volume by perometry at 6 months was 2.03% with a moderate correlation between perometry and BIS at 3 months (r = 0.38) and 6 months (r = 0.37). In 441 patients with 6 months follow-up, the gold standard perometry detected lymphoedema in 44 (10%) patients by 6 months compared to the contralateral arm, whereas BIS measured using the unit L-Dex was positive (showed an increase of an L-Dex of 10) in 103 (21%) patients. Of the 99 patients with 18 months follow-up, 24% have lymphoedema as detected by perometry. When compared with the baseline measurements for perometry and BIS, the month 1 measurements detected fewer cases of lymphoedema by 6 months, 11 (42%) fewer for perometry and 18 (30%) fewer for BIS. 25% of patients reported symptoms before surgery. While 100% of those with lymphoedema at 6 months post-surgery reported symptoms, 23% with no lymphoedema also reported at least one symptom at 6 months. Conclusions Pre-operative measurements should be used as baseline to enable accurate monitoring of lymphoedema development. Symptoms alone are not an accurate predictor of current or future lymphoedema and arm sleeves should not be prescribed for symptoms without measuring arm volume change compared to the contralateral arm. The modest correlation between perometry and BIS at 6 months suggests arm volume measurements remain necessary before and after ANC for monitoring, although longer term follow-up data is required to determine the most sensitive method of predicting lymphoedema.(Funded by NIHR Programme Grant). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-09.

G27 The Lymphatic Phenotype in Turner Syndrome: An Evaluation of Patients Presenting to Three Specialist Primary Lymphoedema Clinics and Literature Review

Aims This study aimed to analyse the medical records of a cohort of 19 Turner Syndrome patients attending three specialist primary lymphoedema clinics to elucidate the key features of the lymphatic phenotype of Turner Syndrome and provide vital insights into its diagnosis, progression and management. Lymphoedema of the hands, feet and cervical region is a common and key diagnostic indicator of Turner Syndrome, present in >60% of patients, though is poorly described in the literature. Methods The study sample of 19 female patients was obtained from specialist primary lymphoedema clinics at three major centres and located by identifying all patients with Turner Syndrome and lymphoedema from hospital databases. Patient and genetic notes were identified through the use of patient-specific numerical identifiers. These notes were thoroughly analysed and examined and any important information inserted into a spreadsheet pro forma. Results The majority of patients presented at birth with 4-limb lymphoedema which often resolved in early childhood but frequently recurred in later childhood. There was 1 case of systemic involvement (e.g. intestinal or pulmonary lymphangiectasia). The swelling was confined to the legs and hands with no facial or genital swelling. The most significant discovery from this research was a pattern observed from the lymphoscintigraphy results, which suggested that the lymphatic phenotype of Turner Syndrome may be due to lymphatic functional hypoplasia of lymphatic tracts. Conclusion Turner Syndrome frequently presents at birth with 4-limb lymphoedema which often resolves in early childhood but may recur at any age. The lymphoscintigraphy results suggested that the lymphatic phenotype in Turner Syndrome may be due to lymphatic functional hypoplasia, a new perspective which may highlight the importance of this test as a baseline assessment of lymphoedema in Turner Syndrome patients.