AIM:The aim of this study was to describe the technique of DCMRL to identify central lymphatic abnormalities in patients with primary lymphatic anomalies and discuss utility of the findings. MATERIALS AND METHODS:Twenty-eight patients with primary lymphatic abnormalities underwent dynamic magnetic resonance imaging (MRI) following injection of gadolinium directly into inguinal lymph nodes at a tertiary lymphovascular referral center. RESULTS:Technical success was achieved in 23 patients (82.1%). Pathological imaging findings included obstructed, hypoplastic, or absent lymphatic channels with collateralization/rerouting or reflux of flow, lymphangiectasia, lymphatic pseudoaneurysms, and lymph leaks. Protocol modifications for improved imaging are highlighted including technical aspects of lymph node injection, image acquisition and MRI parameters. In two patients, imaging findings warranted embolization of the abnormal lymphatic channels with subsequent symptomatic improvement. CONCLUSION:DCMRL has been shown to be a safe, reproducible technique in patients with primary lymphatic anomalies enabling imaging of the central lymphatic system.

Mechanisms underlying human venous valve disease caused by mutations in Foxc2 and connexin47

There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/−2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/−16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants.

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Aim: The aims of this prospective study were (a) to examine the relationship between pre-operative muscle lymph flow and the predisposition to BCRL in women treated by axillary nodal surgery for breast cancer; and (b) to test the 'stopcock' hypothesis that axillary lymph node surgery impairs forearm lymph flow in the short term.Methods: Tc-99m-nanocoll was injected intramuscularly into both forearms of women undergoing surgery for breast cancer. Lymphatic clearance rate constant, k, representing lymph flow per unit interstitial fluid volume, was measured as the fractional disappearance rate of radioactivity from the depot site by gamma camera imaging. Axillary lymph node activity was calculated as percentage injected activity. BCRL was assessed by clinical examination and upper limb perometry.Results: Of 38 pre-operative women, 33 attended at 8 +/- 6 weeks post-operatively and 31 at 58 +/- 9 weeks post-operatively. Seven patients (18%) developed BCRL. Prior to surgery the BCRL-destined patients had a higher mean k (0.0962 +/- 0.034%/min) than non-BCRL patients (0.0830 +/- 0.019%/min) (p = 0.10, unpaired t test). Post-operative k values were not significantly different from pre-operative, in either the ipsilateral (operated) or contralateral limb. Also, post-operative k values did not differ significantly between both upper limbs. Furthermore, there was no significant difference between pre- and post-operative axillary activity.Conclusion: Patients who develop BCRL have high lymph flow pre-surgery, which may predispose them to lymphatic overload and failure. Axillary lymph node surgery has no early, measurable effect on forearm muscle lymph flow despite surgical disruption of routes of lymph drainage. (C) 2014 Elsevier Ltd. All rights reserved.

Introduction: Despite affecting approximately a quarter of all patients undergoing axillary lymph node dissection, the pathophysiology of breast cancer-related lymphoedema (BCRL) remains poorly understood. More extensive loco-regional treatment and higher body mass index have long been identified as major risk factors. This study aims to identify risk factors for BCRL with a specific focus on the potential impact of chemotherapy on the risk of BCRL, in a cohort of consecutive patients treated between 1st January 2010 and 31st December 2012.

Background: Approximately 25% of breast cancer patients who undergo treatment to the axilla develop breast cancer-related lymphoedema (BCRL). The aim of this study was to test the hypothesis that lymphovenous communications (LVCs) open and act as a protective mechanism against the development of BCRL.Methods: Five patients (Group 1) received intradennal injections of (99m)Technetium-labelled autologous erythrocytes into the 2nd ipsilateral hand webspace before and 6-12. weeks following axillary node clearance surgery (ANC). Ten patients at least three years after ANC were also recruited (Group 2); seven had developed BCRL and three had not. Blood was sampled from ipsilateral and contralateral antecubital veins 5, 15, 30, 60, 120 and 180 min post-injection to assess pre-nodal shunting from lymph to blood (LVCs), since nodes block erythrocyte transit. The proportion of activity remaining in the depot was used to calculate the degree of shunting in those with evidence of LVCs.Results: Significant erythrocyte-bound activity, increasing over time, was detected contralaterally in 3 of the 5 patients from Group 1 (none of whom developed BCRL) and 3 of 7 patients with BCRL from Group 2, which indicated the presence of LVCs. The degree of shunting was more marked in those patients who did not develop BCRL compared with those who did.Conclusions: The time-course of erythrocyte-bound contralateral activity indicates transit through lymphovenous communications rather -Shan needle-induced trauma. Lymphovenous communications large enough to transmit erythrocytes are probably constitutional rather than induced. A larger study is warranted to assess any resulting protection against BCRL. (C) 2014 Elsevier Ltd. All rights reserved.

BACKGROUND:Despite affecting approximately one-quarter of all patients undergoing axillary lymph node dissection, the pathophysiology of breast cancer-related lymphoedema (BCRL) remains poorly understood. More extensive locoregional treatment and higher body mass index have long been identified as major risk factors. This study aimed to identify risk factors for BCRL with a specific focus on the potential impact of chemotherapy on the risk of BCRL.METHODS:This was a retrospective analysis of a cohort of consecutive patients with breast cancer treated at a major London regional teaching hospital between 1 January 2010 and 31 December 2012. All patients had node-positive disease and underwent axillary lymph node dissection. Data regarding tumour-, patient- and treatment-related characteristics were collected prospectively. The diagnosis of BCRL was based on both subjective and objective criteria. Multivariable Cox proportional hazards regression was used to assess the association between treatment and risk of BCRL.RESULTS:Some 27.1 per cent of all patients (74 of 273) developed BCRL over the study period. Administration of taxanes showed a strong association with the development of BCRL, as 52 (33.5 per cent) of 155 patients who received taxanes developed BCRL. Multivariable Cox regression analysis demonstrated that patients who received taxanes were nearly three times more likely to develop BCRL than patients who had no chemotherapy (hazard ratio 2.82, 95 per cent c.i. 1.31 to 6.06). No such increase was observed when taxanes were administered in the neoadjuvant setting.CONCLUSION:The present findings suggest that adjuvant taxanes play a key role in the development of BCRL after surgery. This may support the use of taxanes in a neoadjuvant rather than adjuvant setting.

Introduction: Breast cancer-related lymphoedema (BCRL) is a chronic swelling of the upper limb following axillary lymph node surgery. Underlying mechanisms predisposing to BCRL are unclear. This prospective study aims to correlate lymph flow in the upper limb of breast cancer patients pre- and post-axillary lymph node surgery with subsequent development of BCRL.

Historically, primary lymphoedema was classified into just three categories depending on the age of onset of swelling; congenital, praecox and tarda. Developments in clinical phenotyping and identification of the genetic cause of some of these conditions have demonstrated that primary lymphoedema is highly heterogenous. In 2010, we introduced a new classification and diagnostic pathway as a clinical and research tool. This algorithm has been used to delineate specific primary lymphoedema phenotypes, facilitating the discovery of new causative genes. This article reviews the latest molecular findings and provides an updated version of the classification and diagnostic pathway based on this new knowledge.

Introduction: Previous studies have suggested that some women are more susceptible to developing breast cancer-related lymphoedema (BCRL). Our aim was to investigate the hypothesis that there is a constitutional predisposition to BCRL and that this is reflected in abnormal lower limb lymphatic function.

Oculodentodigital syndrome (ODD; OMIM 164200) is a congenital condition with phenotypic features most commonly affecting the face, eyes, dentition and digits. The condition is caused by mutations in the GJA1 gene on chromosome 6. GJA1 codes for connexin 43, a gap junction protein important in providing cell to cell communication and is expressed in lymphatic valves. We present a patient with a clinical and molecular diagnosis of ODD and lower limb lymphoedema. Sanger sequencing of family members confirmed that the missense, p.K206R, GJA1 mutation segregated with the phenotype suggestive of causality. To our knowledge this association has not been reported previously. This is therefore the second connexin gene associated with a lymphoedema phenotype after the recent publication of GJC2 (connexin 47) as a cause of four limb lymphoedema.

Introduction: Breast cancer-related lymphoedema (BCRL) occurs in up to 25% of patients undergoing axillary clearance and 6% undergoing SLNB. The presence or development of lymphovenous communications (LVCs) may protect against BCRL in some women. The aim of this study was to identify peripheral LVCs using intradermal injection of radiolabelled erythrocytes.

Clinical GeneticsVolume 81, Issue 2 p. 191-197 CCBE1 mutations can cause a mild, atypical form of generalized lymphatic dysplasia but are not a common cause of non-immune hydrops fetalis FC Connell, FC Connell Clinical Genetics Department, Guy's and St Thomas' NHS Foundation Trust, London, UK Both these authors contributed equally to this work.Search for more papers by this authorK Kalidas, K Kalidas Medical Genetics Both these authors contributed equally to this work.Search for more papers by this authorP Ostergaard, P Ostergaard Medical GeneticsSearch for more papers by this authorG Brice, G Brice Southwest Thames Regional Genetics Service, St. George's University of London, UKSearch for more papers by this authorV Murday, V Murday Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospital, Glasgow, UKSearch for more papers by this authorPS Mortimer, PS Mortimer Department of Cardiac and Vascular Sciences (Dermatology)Search for more papers by this authorI Jeffrey, I Jeffrey Perinatal Pathology, St George's University of London, London, UKSearch for more papers by this authorS Jeffery, S Jeffery Medical GeneticsSearch for more papers by this authorSahar Mansour, Corresponding Author Sahar Mansour Southwest Thames Regional Genetics Service, St. George's University of London, UKSahar MansourSouthwest Thames Regional Genetics ServiceSt. George's University of LondonLondon SW17 0RE UKTel.: +44 2087250957Fax: +44 2087253444e-mail: smansour@sgul.ac.ukSearch for more papers by this author FC Connell, FC Connell Clinical Genetics Department, Guy's and St Thomas' NHS Foundation Trust, London, UK Both these authors contributed equally to this work.Search for more papers by this authorK Kalidas, K Kalidas Medical Genetics Both these authors contributed equally to this work.Search for more papers by this authorP Ostergaard, P Ostergaard Medical GeneticsSearch for more papers by this authorG Brice, G Brice Southwest Thames Regional Genetics Service, St. George's University of London, UKSearch for more papers by this authorV Murday, V Murday Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospital, Glasgow, UKSearch for more papers by this authorPS Mortimer, PS Mortimer Department of Cardiac and Vascular Sciences (Dermatology)Search for more papers by this authorI Jeffrey, I Jeffrey Perinatal Pathology, St George's University of London, London, UKSearch for more papers by this authorS Jeffery, S Jeffery Medical GeneticsSearch for more papers by this authorSahar Mansour, Corresponding Author Sahar Mansour Southwest Thames Regional Genetics Service, St. George's University of London, UKSahar MansourSouthwest Thames Regional Genetics ServiceSt. George's University of LondonLondon SW17 0RE UKTel.: +44 2087250957Fax: +44 2087253444e-mail: smansour@sgul.ac.ukSearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1111/j.1399-0004.2011.01731.xCitations: 20 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume81, Issue2February 2012Pages 191-197 RelatedInformation

Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used as an agent for post-transplant immunosuppression and the treatment of solid organ and haematological malignancies and hamartomas. Its advantages include a lack of nephrotoxicity and a lower incidence of nonmelanoma skin cancers; adverse effects include delayed wound healing, increased lymphocoele formation and rarely lymphoedema. We report a series of eight cases of severe, sustained, unilateral and bilateral lymphoedema in patients receiving sirolimus for post-transplant immunosuppression, classify their lymphoscintigraphy findings and propose a mechanism of aetiology based on the interaction of mTOR with key mediators of lymphangiogenesis.

BACKGROUND:A 23-year-old male was referred to our clinic with diagnosis of idiopathic isolated growth hormone deficiency. A detailed family history revealed short stature and swelling of legs which only affected females in four generations of his family.METHODS:Combined pituitary function tests revealed growth hormone deficiency, secondary hypothyroidism and hypoprolactinemia in the proband. His mother had hypoprolactinemia and growth hormone deficiency. A diagnosis of inherited combined pituitary deficiency due to a PIT-1 mutation was suspected in view of the short stature with associated multiple pituitary hormone deficiencies.RESULTS:A mutation was identified in PIT-1 (POU1F1), 196C>T, which produces the amino acid change P24L in exon 1. The mutation was also found in the mother of the proband but not in his phenotypically normal half-sister.CONCLUSION:The case shows a novel association of two rare conditions Pit-1 mutation and lipoedema in a family that has not been described before. It also allows formulation of hypothesis on the interaction of growth hormone and sex steroids resulting in abnormal fat distribution in predisposed subjects at the time of puberty.