Lymphatic Failure Research Articles

Symposium Highlight: LYMPHATIC IMAGING AND INTERVENTION IN CENTRAL LYMPHATIC DISORDERS

Advances in lymphatic imaging for both diagnosis and intervention are reviewed, and specific examples given for protein-losing enteropathy, multi compartment lymphatic failure, congestive heart failure. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

Integrating compression therapy into heart failure and lymphoedema management.

Heart failure (HF) and lymphoedema often co-exist, significantly affecting the quality of life and requiring complex management. Heart Failure, characterised by reduced cardiac function, affects around 1 million people in the UK. Lymphoedema, involving lymphatic failure, affects 4 to 29 per 1000 individuals, particularly older adults. Traditionally heart failure management focuses on medication, while lymphoedema relies on compression therapy (CT). The article examines the integration of CT to treat lymphoedema with coexisting HF. Evidence suggests that with careful management and multidisciplinary collaboration, CT can be safely used in stable HF patients to manage lymphoedema, improving overall treatment outcomes and patient wellbeing. This approach requires adherence to guidelines and a holistic, patient-centred care model. Debates about CT for lymphoedema in the presence of HF highlight the need for patient-focused and all-encompassing care. Practitioners must consider the broader context of both conditions and collaborate with colleagues and patients to make informed treatment decisions.

Lymphatic failure and lymphatic interventions: Knowledge gaps and future directions for a new frontier in congenital heart disease

Lymphatic failure is a broad term that describes the lymphatic circulation's inability to adequately transport fluid and solutes out of the interstitium and into the systemic venous circulation, which can result in dysfunction and dysregulation of immune responses, dietary fat absorption, and fluid balance maintenance. Several investigations have recently elucidated the nexus between lymphatic failure and congenital heart disease, and the associated morbidity and mortality is now well-recognized. However, the precise pathophysiology and pathogenesis of lymphatic failure remains poorly understood and relatively understudied, and there are no targeted therapeutics or interventions to reliably prevent its development and progression. Thus, there is growing enthusiasm towards the development and application of novel percutaneous and surgical lymphatic interventions. Moreover, there is consensus that further investigations are needed to delineate the underlying mechanisms of lymphatic failure, which could help identify novel therapeutic targets and develop innovative procedures to improve the overall quality of life and survival of these patients. With these considerations, this review aims to provide an overview of the lymphatic circulation and its vasculature as it relates to current understandings into the pathophysiology and pathogenesis of lymphatic failure in patients with congenital heart disease, while also summarizing strategies for evaluating and managing lymphatic complications, as well as specific areas of interest for future translational and clinical research efforts.

Preliminary report of a thoracic duct-to-pulmonary vein lymphovenous anastomosis in swine: A novel technique and potential treatment for lymphatic failure

ObjectiveThe thoracic duct is the largest lymphatic vessel in the body, and carries fluid and nutrients absorbed in abdominal organs to the central venous circulation. Thoracic duct obstruction can cause significant failure of the lymphatic circulation (i.e., protein-losing enteropathy, plastic bronchitis, etc.). Surgical anastomosis between the thoracic duct and central venous circulation has been used to treat thoracic duct obstruction but cannot provide lymphatic decompression in patients with superior vena cava obstruction or chronically elevated central venous pressures (e.g., right heart failure, single ventricle physiology, etc.). Therefore, this preclinical feasibility study sought to develop a novel and optimal surgical technique for creating a thoracic duct-to-pulmonary vein lymphovenous anastomosis (LVA) in swine that could remain patent and preserve unidirectional lymphatic fluid flow into the systemic venous circulation to provide therapeutic decompression of the lymphatic circulation even at high central venous pressures. MethodsA thoracic duct-to-pulmonary vein LVA was attempted in 10 piglets (median age 80 [IQR 80–83] days; weight 22.5 [IQR 21.4–26.8] kg). After a right thoracotomy, the thoracic duct was mobilized, transected, and anastomosed to the right inferior pulmonary vein. Animals were systemically anticoagulated on post-operative day 1. Lymphangiography was used to evaluate LVA patency up to post-operative day 7. ResultsA thoracic duct-to-pulmonary vein LVA was successfully completed in 8/10 (80.0%) piglets, of which 6/8 (75.0%) survived to the intended study endpoint without any complication (median 6 [IQR 4–7] days). Initially, 2/10 (20.0%) LVAs were aborted intraoperatively, and 2/10 (20.0%) animals were euthanized early due to post-operative complications. However, using an optimized surgical technique, the success rate for creating a thoracic duct-to-pulmonary vein LVA in six animals was 100%, all of which survived to their intended study endpoint without any complications (median 6 [IQR 4–7] days). LVAs remained patent for up to seven days. ConclusionA thoracic duct-to-pulmonary vein LVA can be completed safely and remain patent for at least one week with systemic anticoagulation, which provides an important proof-of-concept that this novel intervention could effectively offload the lymphatic circulation in patients with lymphatic failure and elevated central venous pressures.

Anesthetic challenges in patients with multicompartmental lymphatic failure after Fontan palliation undergoing transcatheter thoracic duct decompression.

Lymphatic flow abnormalities are central to the development of protein losing enteropathy, plastic bronchitis, ascites and pleural effusions in patients palliated to the Fontan circulation. These complications can occur in isolation or multicompartmental (two or more). The treatment of multicompartmental lymphatic failure aims at improving thoracic duct drainage. Re-routing the innominate vein to the pulmonary venous atrium decompresses the thoracic duct, as atrial pressure is lower than systemic venous pressure in Fontan circulation. Transcatheter thoracic duct decompression is a new minimally invasive procedure that involves placing covered stents from the innominate vein to the atrium. Patients undergoing this procedure require multiple general anesthetics, presenting challenges in managing the sequelae of disordered lymphatic flow superimposed on Fontan physiology. We reviewed the first 20 patients at the Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for transcatheter thoracic duct decompression between March 2018 and February 2023. The patients ranged in age from 3 to 26 years. The majority had failed prior catheter-based lymphatic intervention, including selective embolization of abnormal lympho-intestinal and lympho-bronchial connections to treat lymphatic failure in a single compartment. Fourteen had failure in three lymphatic compartments. Patients were functionally impaired (ASA 3-5) with significant comorbidities. Concurrent with thoracic duct decompression, three patients required fenestration closure for the resultant decrease in oxygen saturation. Ten patients had improvement in symptoms, seven had no changes and three have limited follow up. Five (25%) of these patients were deceased as of January 2024 due to non-lymphatic complications from Fontan failure.

Quantitative lymphoscintigraphy of the lower limbs for the diagnosis of phlebolymphoedema.

Phlebolymphoedema is caused by the interaction of the venous and lymphatic systems in a state of chronic venous insufficiency in which increased microvascular filtration causes an increased rate of lymph production. Lymphatic drainage rate increases in response, but this is unsustainable and can cause lymphatic failure and oedema. We hypothesise that in phlebolymphoedema we could measure unusually high lymphatic drainage while the lymph system is still fully functional. Patients referred for lymphoscintigraphic investigation of swollen legs between April 2021 and December 2022 were reviewed. Quantitative lymphoscintigraphy was performed following the technique of Keramida et al . (2017) and ilio-inguinal nodal uptake (IIQ%) was calculated. The presence of scintigraphic features of increased lymph production was noted for each limb. A total of 39 patients were reviewed (78 limbs, 29F, 10M). Seven limbs were identified with supranormal lymphatic function (IIQ > 30%) plus three borderline. Of these 10 limbs, all had at least two scintigraphic features of increased lymph production. Quantitative lymphoscintigraphy, although developed for diagnosing abnormally low lymphatic function, may also have utility at the upper end of the spectrum for identifying chronic venous insufficiency. An IIQ% upper normal limit of 30% could be used to diagnose venous insufficiency as the cause for limb swelling. This is of note for patients of large body habitus in whom venous ultrasound is difficult.

Occlusion Pressure of the Thoracic Duct in Fontan Patients With Lymphatic Failure: Does Dilatation Challenge Contractility?

The Fontan circulation challenges the lymphatic system. Increasing production of lymphatic fluid and impeding lymphatic return, increased venous pressure may cause lymphatic dilatation and decrease lymphatic contractility. In-vitro studies have reported a lymphatic diameter-tension curve, with increasing passive stretch affecting the intrinsic contractile properties of each thoracic duct segment. We aimed to describe thoracic duct occlusion pressure and asses if thoracic duct dilation impairs contractility in individuals with a Fontan circulation and lymphatic failure. Central venous pressure and thoracic duct measurements were retrospectively collected from 31 individuals with a Fontan circulation. Thoracic duct occlusion pressure was assessed during a period of external manual compression and used as an indicator of lymphatic vessel contractility. Measurements of pressure were correlated with measurements of the thoracic duct diameter in images obtained by dynamic contrast-enhanced MR lymphangiography. The average central venous pressure and average pressure of the thoracic duct were 17 mm Hg. During manual occlusion, the thoracic duct pressure significantly increased to 32 mm Hg. The average thoracic duct diameter was 3.3 mm. Thoracic duct diameter correlated closely with the central venous pressure. The rise in pressure following manual occlusion showed an inverse correlation with the diameter of the thoracic duct. Higher central venous pressures are associated with increasing diameters of the thoracic duct. When challenged by manual occlusion, dilated thoracic ducts display a decreased ability to increase pressure. Dilatation and a resulting decreased contractility may partly explain the challenged lymphatic system in individuals with a Fontan circulation.

Transcatheter Thoracic Duct Decompression for Multicompartment Lymphatic Failure After Fontan Palliation.

Lymphatic embolization therapy has proven effective for Fontan failure from plastic bronchitis or protein-losing enteropathy but not when multiple lymphatic compartments are involved; furthermore, embolization does not alter the underlying pathophysiology of lymphatic dysfunction. A technique for transcatheter thoracic duct decompression (TDD), rerouting the thoracic duct to the pulmonary venous atrium to treat multicompartment lymphatic failure is described and early outcomes presented. Initially covered stents were used to channel the innominate vein flow inside of the cavopulmonary pathway into the pulmonary venous atrium. A modified approach was developed where covered stents redirected innominate vein directly to the left atrium via an extravascular course. Baseline and follow-up data on all patients undergoing TDD were reviewed. Twelve patients underwent TDD between March 2018 and February 2021 at a median age of 12 (range: 2-22) years. Lymphatic failure occurred in median of 3 compartments per patient (protein-losing enteropathy, ascites, pleural effusions, plastic bronchitis); 10 patients had lymphatic embolizations before TDD. TDD method was intra-Fontan tunnel in 4, direct approach in 7, and other in 1. There were no major procedural complications; 6 patients underwent subsequent procedures, most commonly to treat endoleaks. Lymphatic failure resolved in 6 patients, improved in 2, and was unchanged in 4 at 6 (range: 1-20) months follow-up. One patient died after TDD from Fontan failure. TDD is a promising new treatment for the failing Fontan physiology from multicompartment lymphatic failure. Additional work is needed to refine the technique and define optimal candidates.

Chylous ascites as hernia content in a prematurely born infant with bilateral inguinal hernia

Abstract We present the case of an infant born at 29 6/7 weeks of gestational age, who underwent semi-elective surgical repair for bilateral inguinal hernia at four months of age. During surgery, chyle was unexpectedly found in the hernia sac and abdominal cavity. Chylous ascites is a rare condition in infants. Possible etiologic factors include (surgical) trauma, congenital lymphatic anomalies, infectious diseases, liver cirrhosis, cardiac failure, neoplasms and metabolic conditions. A thorough diagnostic workup for chylous ascites was performed to rule out pre-existent underlying pathologies, and the child was temporarily placed on a medium-chain triglyceride diet. An ultrasound after two weeks showed no recurrence of ascites and the child was successfully placed on regular formula feeding. No symptoms occurred afterwards. Based on the clinical course and results of additional investigations, this rare phenomenon has most likely occurred due to obstruction and potential rupture of lymphatic structures due to mechanical effects following intermittent incarceration and subsequent repetitive manual reduction of the symptomatic hernia including bowel loops as content of the hernia sac.

Lymphadenectomy issues in endometrial cancer.

ObjectivesThis review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of lymphadenectomy for endometrial cancer.MethodsWe summarized previous reports on the preoperative prediction models for LNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, we compared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) to examine the survival benefit of lymphadenectomy in endometrial cancer, and described the details of JCOG1412.ResultsLymphadenectomy has been omitted for 64 endometrial cancer patients who met low-risk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphatic failure has been observed. Other two models also produced comparable results. Two randomized phase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrial cancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aortic lymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients at risk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, including lower limit of the number of resected nodes, and submission of photos of dissected area to evaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showed that the quality of lymphadenectomy has been well-controlled in JCOG1412.ConclusionOur strategy seems reasonable to omit lymphadenectomy and could be generalized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms of the quality of surgical procedures, which would draw the bona-fide conclusions regarding the therapeutic role of lymphadenectomy for endometrial cancer.

Lymphatic Decompression Concomitant With Fontan/Kreutzer Procedure: Early Experience.

To present a strategy for identifying patients at risk of lymphatic failure in the setting of planned Fontan/Kreutzer completion, allowing a tailored surgical approach. Since January 2017, clinical evaluation before performance of the Fontan/Kreutzer procedure included T2-weighted magnetic resonance imaging (MRI) lymphangiography. Thoracic lymphatic abnormalities were categorized using a scale of I to IV according to progression of severity. Patients with severe lymphatic abnormalities (types III and IV) underwent Fontan/Kreutzer with lymphatic decompression via connection of the left jugular-subclavian junction containing the thoracic duct to the systemic atrium (group A). Thirteen patients were enrolled. Magnetic resonance imaging showed type I abnormalities in four cases (30.7%), II in four (30.7%), III in two (15.3%), and IV in three (23.3%). Patients in types III and IV underwent a Fontan/Kreutzer with lymphatic decompression (group A, n = 5), while patients in types I and II underwent a fenestrated extracardiac Fontan/Kreutzer procedure without lymphatic decompression (group B, n = 8). Preoperatively, there were no differences in age, weight, ventricular dominance (right vs left), superior vena cava pressure, incidence of chylothorax after previous superior cavopulmonary anastomosis (Glenn), or need for concomitant procedures at Fontan/Kreutzer completion. There were no differences in procedural times between the groups, nor were there differences in mortalities and Fontan/Kreutzer takedowns. There were no statistically significant differences in early and late morbidity between the two groups with the exception of total volume of effusions output postoperatively. At median follow-up of 18 months (range, 4-28 months), all patients in group A are in New York Heart Association class 1 with no differences between groups in arterial oxygen saturation. Lymphatic decompression during Fontan/Kreutzer procedure was successfully performed in patients identified by MRI as predisposed to lymphatic failure. A larger cohort of patients and longer follow-up are required to determine the efficacy of this approach in preventing early- and long-term Fontan/Kreutzer failure.

Prevalence and Cause of Early Fontan Complications: Does the Lymphatic Circulation Play a Role?

BackgroundRecent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein‐losing enteropathy. However, the role of the lymphatic circulation in early post‐Fontan outcomes is not well defined.Methods and ResultsThis was a retrospective, single‐center study of patients undergoing first‐time Fontan completion from 2012 to 2017. The primary outcome was early Fontan complication ≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions in the absence of Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2‐weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty‐eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high‐grade lymphatic abnormalities had 6 times greater odds of developing early complications (P=0.001).ConclusionsThere is substantial morbidity in the early post‐Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher‐grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.

Indocyanine green lymphography findings in older patients with lower limb lymphedema

ObjectiveLymphedema is classified as primary or secondary according to the underlying cause. Primary lymphedema is hereditary and is considered a consequence of an inherited abnormality of the lymphatic system. Secondary lymphedema, however, is a consequence of lymphatic failure resulting from trauma, parasitic infection, or iatrogenic obstruction. Primary lymphedema is divided into three broad groups, namely, lymphedema congenita, lymphedema praecox, and lymphedema tarda. With the exception of lymphedema tarda, it is thought that age-related deterioration in lymphatic pump function is caused by oxidative stress. The aim of this study was to evaluate and to classify indocyanine green (ICG) lymphography findings in patients with lower limb lymphedema to ascertain whether there is a pattern to age-related deterioration. MethodsThere were 56 patients (104 edematous lower limbs) who had undergone ICG lymphography and for whom the lower extremity lymphedema (LEL) index had been calculated enrolled in this study. Specific inclusion criteria were used to exclude other causes of edema. ICG lymphography images were recorded in the plateau phase (12-18 hours after injection), when no further changes of images would be expected. The LEL index was calculated by summation of the squares of the circumference for five areas in each lower extremity divided by the body mass index. ResultsThe clinical lymphedema pattern was determined as bilateral in 48 patients and unilateral in 8 patients. Patients with bilateral lymphedema were significantly older than those with unilateral lymphedema (76.40 ± 8.03 years vs 53.13 ± 14.12 years; P < .01). The ICG lymphography pattern was categorized as linear, low enhancement (LE), distal dermal backflow (DB), or extended DB in bilateral lymphedema. ICG lymphography showed the DB pattern on both the thigh and lower leg regions in all eight legs with unilateral lymphedema. There were also significant between-group differences in the LEL index (linear vs distal DB, P < .05; linear vs extended DB, P < .01; linear vs unilateral, P < .01; LE vs extended DB, P < .01; LE vs unilateral, P < .01; distal DB vs extended DB, P < .05; and distal DB vs unilateral, P < .01). ConclusionsIn this study, unilateral lymphedema, with its younger age at onset, severity, and unilateral dominance, corresponded to lymphedema tarda. In contrast, bilateral lymphedema corresponded to senile lymphedema, which is distinct from primary lymphedema in general and lymphedema tarda in particular. Age-related deterioration in lymphatic pump function rather than iatrogenic obstruction or genetic abnormality is likely to account for the characteristic older age at onset of lymphedema and its progression from the distal region.

Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis.

Lymphatic failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic factors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inflammation was studied by administering VEGF-receptor 3 (VEGF-R3) inhibitors to the mouse model of colitis using dextran sulfate sodium and evaluating platelet migration to LVs. The inhibitory effect of platelets on lymphangiogenesis was investigated in vivo by administering antiplatelet antibody to the colitis mouse model and in vitro by coculturing platelets with lymphatic endothelial cells. Although mRNA expressions of lymphangiogenic factors such as VEGF-R3 and podoplanin were significantly increased in the inflamed mucosa of patients with IBD compared with those with quiescent mucosa, there was no difference in LV density between them. In the colitis model, VEGF-R3 inhibition resulted in aggravated colitis, decreased lymphatic density, and increased platelet migration to LVs. Administration of an antiplatelet antibody increased LV densities and significantly ameliorated colitis. Coculture with platelets inhibited proliferation of LECs in vitro. Our data suggest that despite elevated lymphangiogenic factors during colonic inflammation, platelet migration to LVs resulted in suppressed lymphangiogenesis, leading to aggravation of colitis by blocking the clearance of inflammatory cells. Modulating the interaction between platelets and LVs could be a new therapeutic means for treating IBD.

Physiology and pathophysiology of the lymphatic system. Research results and further prospects

The review summarizes own research and literature on the role of the lymphatic system in a number of physiological and pathological conditions. The typical reaction of lymph circulation seen in shock, acute diffuse peritonitis, in postoperative period is the lymph flow volumetric rate increase. Mobilization of the lymphatic system, extravascular fluid and proteins in well-studied emergencies is explained considering the role of the lymphatic system as a natural source of circulating blood volume regulation and serum proteins replacement («autotransfusion»). These pathological processes are associated with progression of lymphatic failure on the late terms. The principle of lymph circulation targeted stimulation as a way to detoxify the body using hormones and procaine (Novocain) blockade of splanchnic nerves and the borderline sympathetic trunks was proposed based on modeled acute peritonitis. Increased microcirculation and central lymph flow, alterations in resorption, transport and filtration barrier function of the lymphatic system, as well as morphologic and functional reorganization of the lymph nodes were revealed in fever of different duration. Of particular interest are studies on the role of the lymphatic system in the immediate and long-term body adaptation to physical stress. Activation of central lymph circulation in adequate dynamic loads correlated with changes in the system lymph microcirculation (acceleration of lymph flow, increased peristalsis of the lymph microvessels walls and contractile activity of their valves). Extreme physical exhaustion was accompanied by expressed lymphovascular, extravascular and intravascular changes in the microvasculature. Lymphatic failure, as well as structural microcirculation impairments in a trained body occur only in extreme physical stress. Thus, the lymphatic system is involved in many physiological and pathological processes; its functional condition affects the course and outcome of the disease. Therefore, the treatment of the diseases requires, among other measures, correction of lymph formation and circulation (stimulation or inhibition, endolymphatic treatment, thoracic duct drainage, lymphosorption, blockade of nodal pathways and other methods - depending on the specific disease).

Differentiation of High and Low Output Lymphatic Failure Using Qualitative Lymphangioscintigraphy.

To use qualitative lymphangioscintigraphy (LAS) findings to differentiate leg edema caused by high and low output lymphatic failure. LAS was performed in legs with secondary lymphedema (LE), i.e., low output failure (N = 79), and functional venous insufficiency (FVI), i.e., high output failure (N = 56), and normal legs (N = 26). Whole body images were obtained, 15, 60, and 180 min after technetium-99m injection. The rate and timing of visualization of lymphatic structures, washout out of tracer, and presence of dermal backflow were assessed. The most significant finding for differentiating LE from other conditions was not the visualization of lymphatic structures, but the washout of the tracer from the leg trunk (LE 27%, FVI 100%, normal leg 100%, P <.0001). On the other hand, the most significant finding for differentiating FVI from other legs was the visualization of inguinal lymph nodes at 15 min (LE 11%, FVI 82%, normal leg 8%, P <.0001). We found that the lack of washout from the leg trunk was most suggestive of a low output status of the lymphatic system, while earlier visualization of inguinal lymph nodes was suggestive of a high output status.

Clinical features of distant lymph node metastasis in early-stage extranodal nasal-type NK/T-cell lymphoma after treatment

Objective To analyze the incidence and risk factors for distant lymph node metastasis in stage Ⅰ E and Ⅱ E upper aerodigestive tract natural killer (NK)/T-cell lymphoma (UADT-NKTCL) after treatment.Methods From December 1979 to December 2012,468 patients with stage Ⅰ E and Ⅱ E UADTNKTCL were treated; 170 patients were treated with radiotherapy alone,19 patients with chemotherapy alone,278 patients with radiotherapy and chemotherapy,and one patient with anti-inflammation therapy.The incidence of distant lymph node metastasis was calculated by the Kaplan-Meier method.Results The median follow-up was 35 months.Thirty-two patients had distant lymph node metastasis,accounting for 6.8％ of all patients and 19.8％ of 162 patients who had disease progression or recurrence; the 2-year incidence of distant lymph node metastasis was 6.4％.Twenty-three (71.9％) of the 32 patients had distant organ metastasis.Mesenteric lymph nodes were most affected in distant lymph node metastasis.The univariate analysis showed that extranasal UADT-NKTCL,stage Ⅱ E,and not achieving a complete response (non-CR) after the first course of treatment were high-risk factors for distant lymph node metastasis.The multivariate analysis showed that stage ⅡE and non-CR after the first course of treatment were identified as independent risk factors for long-term recurrence,with hazard ratios of 2.82 (1.37-5.82,P =0.005) and 3.01 (1.16-7.78,P =0.023).For patients with stage Ⅱ E disease,those receiving combined-modality therapy had a significantly lower incidence of distant lymph node metastasis than those receiving radiotherapy alone and chemotherapy alone (2-year incidence of distant lymph node metastasis:12.5％ vs 35.1％ and 50.0％,P =0.011).Conclusions The incidence of distant lymph node metastasis is low in patients with stage Ⅰ E and Ⅱ E UADT-NKTCL after treatment.However,the patients with stage Ⅱ E disease or nonCR after the first course of treatment still have a high risk of distant lymph node metastasis.Patients with stage Ⅱ E UADT-NKTCL should be treated by combined-modality therapy to reduce the incidence of distant lymph node metastasis. Key words: NK/T cell lymphoma/radiotherapy; Combined-modality therapy; Distant lymphatic failure; Factor analysis

PT176 Women are at risk of procedural complications following percutaneous coronary intervention but have comparable 12 month outcomes

Breast cancer related lymphoedema (BCRL), the chronically swollen arm of patients that have been treated for breast cancer, is no longer considered to be a result of lymphatic obstruction as recent studies have identified failing peripheral lymphatic function as a principal contributing factor. The aetiology and pathophysiology that results in this lymphatic failure is not clearly understood, but it can occur with minimal or even in some cases no damage to the axillary lymph nodes, and evidence suggests that some patients are pre-disposed to develop the disease, and have poor lymphatic function in their non-affected arms. It has been shown that interstitial forces such as hydrostatic pressure, and interstitial fluid velocity, can regulate both lymph flow, and lymph formation, and there is good evidence that interstitial forces are dysregulated in lymphoedema patients. Here I outline a hypothesis for how dysregulation of interstitial parameters could contribute to the generation of breast cancer related lymphoedema, by combining disparate strands of current evidence on the molecular and physiological control of interstitial and lymph flows. One mechanism by which lymphoedema could be generated is that a reduction in interstitial velocity results in increased VEGF-C production, which in low flow conditions, instead of acting on the lymphatics to increase pumping and lymphangiogenesis, acts on vasculature to increase fluid filtration. The resulting increase in interstitial pressure restores flow, but at the expense of increased volume and hence oedema. The evidence supporting the hypothesis and possible tests of it are presented and discussed.

Emerging roles of lymphatics in inflammatory bowel disease

The mobilization and recruitment of blood and lymphatic vasculatures are widely described in inflammatory bowel diseases (IBDs). Although angiogenesis contributes to intense gut inflammation, it remains unclear whether and when lymphangiogenesis amplifies or protects in IBD. The prolonged maintenance of lymphatic (over blood vessels) in inflammation indicates that lymphatic-blood vessel interactions may regulate IBD pathogenesis and restitution. Although lymphatic expansion helps to restore fluid balance and clear cytokines and immune cells, lymphatic failure results in accumulation of these factors and exacerbates IBD. Lymphatic obstruction and remodeling may impair lymphatic pumping, leading to repeated rounds of lymphangiogenesis. Early descriptions of Crohn's disease and ulcerative colitis describe colon lymphatic congestion, remodeling, expansion, and many other features that are recapitulated in experimental IBD and also by intestinal lymphatic obstruction, supporting lymphangitis as a cause and consequence of IBD. Growth factors, cytokines, gut flora, Toll receptors, and leukocytes all regulate inflammation and gut lymphatic remodeling in IBD. This review summarizes the importance of lymphatics and lymphangiogenesis in IBD etiology that may be useful in diagnosis and therapy of gut inflammation.

Lymphoedema Presenting with Pleural Effusion: A Case Report

Lymphatic obstruction either congenitally determined (primary) or by a consequence of acquired lymphatic failure because of obstruction or damaged lymphatics (secondary). Milroy disease is an example of primary lymphoedema where edema is present at birth or soon thereafter. A 16 year old young boy presented with bilateral leg with scrotal oedema since birth with ups and downs of his symptoms. According to the statement of the mother the boy was seen by several physicians and also attended several tertiary hospitals in Dhaka city and eventually was diagnosed as a case of Milroy disease in 2003. Patient was in a reasonably stable condition till July 2008 when he developed massive pleural effusion on right side and chylous fluid was aspirated. After that he developed five episodes of right sided pleural effusion at one to three month interval. Thoracic surgeon was consulted and intra thoracic tube drainage and pleurodesis was done on 19. 02. 2009. After couple of weeks repeat chest x-ray revealed left sided pleural effusion and again left sided pleurodesis was performed. He is now clinically stable except mild oedema in his both feet. DOI: 10.3329/bsmmuj.v3i1.5514 BSMMU J 2010; 3(1): 40-43