Chylous Effusion Research Articles

Lymphangioleiomyomatose

LAM is one of the rare lung diseases. Approximately 200-400 female patients are to be expected in Germany. Only rare reports exist describing a male LAM patient. LAM exists in two forms: a spontaneous mosaic mutation (S-LAM) and a germ line mutation resulting in a combination of pulmonary and systemic symptoms called tuberous sclerosis (TSC-LAM). Although the influence of estrogen is not yet entirely recognized, pregnancy and estrogen containing anticonception will worsen the course of the disease. Ten year prognosis of the disease is well over 80% but variability is large. Rapid progression exists.The clinical picture of S-LAM is dominated by pneumothorax, chylous pleural effusions, dyspnoea upon exertion. (HR) CT demonstrates the easily recognizable and characteristic cystic transformation of the parenchyma. The cellular sequels of the disease involve constant activation of the mTORC1 complex with protein synthesis, proliferation, enzymatic parenchymal transformation, improved cellular survival and metastasis into the lungs most likely from an extrapulmonary source. Following extensive research on the pathologic activation of the mTORC1 pathway, an initial way of halting progression has been found in using mTORC1 inhibitors (Sirolimus, Everolimus). Complimentary strategies are currently investigated in order to improve the therapeutic effect. These measures will improve LAM prognosis in the future. Therapy resistant LAM is a valid indication for lung transplantation.

Octreotide for chylous effusions in congenital diaphragmatic hernia

Background/PurposeChylothorax is a frequent complication in congenital diaphragmatic hernia (CDH) infants and is associated with significant morbidity. The optimal treatment strategy remains unclear. We hypothesize that octreotide decreases chylous effusions in infants with CDH. MethodsThis is a retrospective study of all infants with CDH admitted to our institution from October 2006 to October 2011. ResultsEleven (12%) infants developed a chylothorax. Five infants were managed conservatively with thoracostomy and total parenteral nutrition. Six infants were started on octreotide therapy. None of the infants required surgical intervention to stop the effusion. There was no significant difference in survival to discharge, length of stay, or average daily chest tube output between groups. There appeared to be a temporally associated drop in chest tube output upon initiation of octreotide in two infants; however, the overall rate of decline in chest tube drainage was unchanged. In addition, there were infants in the conservative group who demonstrated a similar drop in daily chest tube output despite the absence of octreotide. ConclusionsOur data suggest that the majority of chylous effusions in CDH infants resolve with conservative therapy alone.

A case of spontaneous chylous pericardial effusion in Poland syndrome

Chylous pericardial effusion is an uncommon entity that is most commonly associated with post-cardiac surgery, in particular aortic valve and minimally invasive cardiac surgery. Post-radiation therapy, infection, mediastinal neoplasm, lymphoma and a small group of idiopathic, spontaneous chylous pericardial effusion have also been reported as the causes. Here, we report a rare case of pericardial effusion secondary to chylous fistula in a 63-year-old man with Poland syndrome. The case highlights an unusual thoracic duct anomaly as a cause of our reported chylous pericardial effusion.

Efficacy of Sirolimus Therapy for Chylous Effusions in Lymphangioleiomyomatosis

Efficacy of Sirolimus Therapy for Chylous Effusions in Lymphangioleiomyomatosis

An aggressive form of non-Hodgkin's lymphoma with pleural and abdominal chylous effusions: A case report and review of the literature

Serous effusions, including pleural, abdominal and pericardial effusions, are complications of lymphoma. Among these types, pleural effusions are the most common to be observed. However, the involvement of the abdominal or pericardial cavity is rare. An impairment of the lymphatic drainage and direct infiltration have been identified to play significant roles in effusion formation. Multiple techniques, including cytological exams, immunochemistry and cytogenetics, have been applied in the clinic to access the qualities of the effusions and to attain a fast and precise diagnosis. Serous effusions are associated with a poor outcome for patients with lymphoma. The present study describes the case of a 28-year-old male patient with aggressive non-Hodgkin's lymphoma (NHL) involving pleural and abdominal chylous effusions.

Two cases of chylopericardium after aortic valve surgery

Chylopericardium is a rare clinical condition. It is largely idiopathic but could be iatrogenic from breached thoracic duct collaterals or secondary to thoracic duct flow obstruction. We describe 2 patients seen in a single cardiothoracic center within 6 weeks, and detail the clinicopathologic correlation of an unusual complication of cardiac surgery, as well as provide an algorithm for the diagnosis and management of postcardiotomy pericardial chylous effusion.

The efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare disease caused by dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. However, the optimal dose for the treatment of LAM remains unclear. We conducted a retrospective, observational study of 15 patients with LAM who underwent sirolimus therapy for more than 6 months. The efficacy was evaluated by reviewing the patients' clinical courses, pulmonary function and chest radiologic findings before and after the initiation of sirolimus treatment. All patients had blood trough levels of sirolimus lower than 5ng/mL. Sirolimus treatment improved the annual rates of change in FVC and FEV1 in the 9 patients who were free from chylous effusion (FVC, -101.0 vs. +190.0mL/y, p=0.046 and FEV1, -115.4 vs. +127.8mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start of sirolimus treatment; the chylothorax resolved completely within 1-5 months of treatment in 6 of these cases. These results resembled those of previous studies in which blood trough levels of sirolimus ranged from 5 to 15ng/mL. Low-dose sirolimus (trough level, 5ng/mL or less) performed as well as the higher doses used previously for improving pulmonary function and decreasing chylous effusion in patients with LAM.

Thoracic duct embolization for the management of chylothoraces

The aim is to inform the reader on the recent advancements in the minimally invasive treatment of chylothorax. Intranodal lymphangiography has been demonstrated to be a superior alternative to traditional pedal lymphangiography for thoracic duct embolization (TDE). TDE is associated with less morbidity and better clinical success than conservative management or surgical intervention in both traumatic and nontraumatic causes of chylothorax. TDE embolization in the pediatric population was found to be feasible. Recent advances in the lymphangiography techniques and the accumulation of experience in treating chylous effusions have significantly broadened the adoption of TDE to treat chylothorax. TDE for traumatic chylothorax has been demonstrated to be less morbid and more effective than surgical and conservative treatment. In cases of nontraumatic chylothorax, the patient has to be evaluated by MRI and lymphangiography to exclude causes of chylothorax which cannot be managed by interruption of the thoracic duct (e.g. lymphatic malformations or chylous ascites). Future advancements in noninvasive imaging of the thoracic duct and imaging guidance during TDE will continue to refine the percutaneous management of chylous effusions.

Nephrectomy Via Ventral Median Celiotomy in Equids

To report technique for, and outcome after, nephrectomy through a ventral median celiotomy in equids. Case series. Equids with unilateral renal disease (n = 6), aged 2 months to 18 years, weighing 90-434 kg. A ventral median celiotomy was used to access the left or right kidney. To facilitate surgical exposure, the small intestine was reflected towards the diaphragm using laparotomy sponges and the ascending colon was exteriorized and in some cases evacuated. The peritoneum over the affected kidney was incised and blunt dissection used to free the kidney from the retroperitoneal fat, then the renal artery, vein, and ureter were isolated and ligated. Abdominal lavage with sterile saline solution was performed before abdominal closure. Four horses, 1 donkey, and 1 mule had unilateral nephrectomy to treat verminous nephritis (1), idiopathic hematuria (1), and ectopic ureter (4). A ventral median approach provided adequate access to the kidney in all 6 cases. Two horses had postoperative complications (peritonitis, chylous abdominal effusion) that resolved with medical therapy. No complications attributable to nephrectomy were reported by the owners upon follow-up 1-8 years after surgery. A ventral median approach for nephrectomy can be used for unilateral nephrectomy in equids weighing up to 434 kg.

Unusual complication after permanent pacemaker insertion

This 83-year-old woman had a left sided AAI pacemaker inserted via subclavian puncture in 2007 for sinus node disease. It was complicated by a chylous effusion of the left pacemaker site, which was initially managed with aspiration and pressure dressing. Four years …

Lymphangioleiomyomatosis: current and future.

Lymphangioleiomyomatosis is a rare slowly progressive lung disease that affects almost exclusively young women of reproductive age. It occurs sporadically or in association with Tuberous Sclerosis Complex. LAM is characterized by cystic remodeling of the lung parenchyma, due to proliferation of abnormal smooth muscle-like LAM cells and presence of extra pulmonary manifestations such as lymphadenopathy, angiomyolipomas and abdominal lymphangioleiomyomas. The most common clinical manifestations are progressive dyspnea on exertion, pneumothorax and chylous effusions. Currently there is no curative treatment for the disease, but the ongoing study of the genetic and molecular pathways implicated in the pathogenesis of the disease could lead to targeted therapy.

Diffuse Pulmonary Lymphangiomatosis

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by infiltration of the lung, pleura and mediastinum with thin-walled lymphangiomas. DPL can result in mass effect from infiltrative disease, restrictive and obstructive pulmonary physiology, chylous effusions and respiratory failure. The present article discusses clinical, radiographic and pathological features, and treatment options for DPL.

Thoracic Duct Embolization for Nontraumatic Chylous Effusion: Experience in 34 Patients

Thoracic duct embolization (TDE) is an acceptable alternative procedure for treating traumatic chylothorax. The purpose of this study is to demonstrate efficacy of TDE in treating nontraumatic chylous effusions.A retrospective review of 34 patients was conducted assessing technical and clinical success of TDE for nontraumatic chylous effusions.Thirty-four patients (mean age, 59 years; 27 female patients) with nontraumatic chylous effusions underwent TDE. Presentations included 21 unilateral chylothoraces (61.8%), nine bilateral chylothoraces (26.5%), two isolated chylopericardiums (5.9%), and two pleural effusions with chylopericardium (5.9%). TDE was technically successful in 24 of 34 patients (70.6%). The thoracic duct could not be catheterized in four of 34 (11.8%). Cisterna chyli was not visualized in six of 34 patients (17.6%), and, thus, TDE was not attempted. Follow-up was available for 32 patients. Four lymphangiographic patterns were observed: (1) normal thoracic duct in 17.6% of patients (six of 34), (2) occlusion of thoracic duct in 58.8% (20 of 34), (3) failure to opacify thoracic duct in 17.6% (six of 34), and (4) extravasation of chyle in 5.9% (two of 34). Clinical success varied with the lymphangiographic pattern. The clinical success rate was 16% (one of six) in cases of normal thoracic duct, 75% (15 of 20 patients) in occlusions of the thoracic duct, 16% (one of six) in cases of failure to opacify the thoracic duct, and 50% in two cases of chyle extravasation. Lymphangiography alone cured two patients (6.5%).TDE was most successful in cases of thoracic duct occlusion and extravasation. Lymphangiography is important for identifying the cause of chylous effusions and selecting patients who benefit most from TDE.

Dramatic Response to Sirolimus in Lymphangioleiomyomatosis

Depatrment of Respirology, University of Toronto, Toronto General Hospital, Toronto, Ontario Correspondence: Dr Dmitry Rozenberg, Depatrment of Respirology, Toronto General Hospital, 9N 965 – 585 University Avenue, Toronto, Ontario M5G 2N2. Telephone 416-340-4591, fax 416-340-3109, e-mail dmitry.rozenberg@uhn.ca A 41-year-old woman presented with a one-year history of progressive dyspnea, early satiety and abdominal cramping. A clinical diagnosis of lymphangioleiomyomatosis (LAM) was made based on a confirmed right-sided chylous effusion (milky, exudative and triglyceride level of 52.6 mmol/L) and characteristic cystic changes on a highresolution computed tomography scan of the chest (Figure 1). A large left-sided retroperitoneal lymphangioleiomyoma supported the diagnosis (Figure 2), with no renal angiomyolipoma or clinical evidence of tuberous sclerosis. She was started on sirolimus therapy, which resolved her dyspnea and abdominal symptoms within six months. Her forced expiratory volume in 1 s (FEV1) (1.6 L) and FVC (2.1 L) had markedly improved during this time interval to 2.6 L and 4.2 L, respectively. Her chest x-ray demonstrated almost complete resolution of the right pleural effusion (Figure 3) and the lymphangioleiomyoma had also decreased in size (Figure 4). The patient remains clinically stable on sirolimus with few side effects and her FEV1 and FVC on therapy at nine months increased to 3.3 L (96%) and 4.8 L (118%), respectively. The present case is a dramatic example of a chylous pleural effusion and massive intra-abdominal lymphangioleiomyoma responding to sirolimus therapy. images in respiratory meDicine

A Case of Successful Octreotide Treatment for Chylous Leakage after Neck Dissection

Recently, octreotide has been reported to be effective in the treatment of some cases of chylothorax and chylous peritoneal effusion. However, there are few reports on the use of octreotide in the fields of otorhinolaryngology and head-and-neck surgery. Herein, we present a case in which octreotide treatment was found to be beneficial to arrest chylous fluid leakage following neck dissection. A 59-year-old woman with thyroid cancer and neck lymph node metastasis underwent total thyroidectomy with bilateral conservative D3a neck dissection. During the operation, the thoracic duct was cut and the tissue surrounding the chylous leakage was sutured and ligated. The patient was started on a low-fat diet on the third postoperative day (POD), and immediately, a large quantity of chylous fluid was found to drain out of the drainage tube. Intermittent subcutaneous administration of octreotide at a dose of 100 μg twice a day was started on the fourth POD. The chylous leakage from the drainage tube started to decrease noticeably from the day after the start of octreotide administration, almost stopping completely on the seventh POD. On the 12th POD, oral intake was resumed, however, no chylous fluid leakage was detected. The patient was discharged from the hospital on the 24th POD. Thus, octreotide appears to be extremely effective for controlling chylous leakage after operation, and treatment with octreotide should be considered before attempting any surgical intervention.

Are There Early Clinical Factors to Decide Early Surgical Management for Secondary Chylothorax? A Review of 32 Cases

Background: Chylothorax may be primary (spontaneous) or secondary and more often arising as a postoperative complication of thoracic surgery. It occurs when the thoracic duct or its lymphatic tributaries become blocked or perforated or divided resulting in a chylous pleural effusion. Loss of chyle leads to nutritional deficiencies, dehydration, ionic perturbation and lymphocytes leaks thus increasing the vulnerability for infections and respiratory dysfunction. It is a life-threatening complication increasing the postoperative hospital stay. Management of chylothorax is firstly medical which leads to the cessation of leaks in most of the cases. Surgical treatment by thoracic duct ligation is sometimes necessary after failure of medical treatment. The appropriate time for surgical treatment is a subject of controversy. Methods: Reviewing a series of patients treated between 2000 to 2010 in a single center with the same protocol management, the aim of the study was to identify early clinical variables allowing early surgical treatment in postoperative chylothorax. Results: Thirty-two patients were identified in the study period. There were 21 males (65.6%) and 11 females (34.4%) with a mean age of 55.7 years (range from 9 to 79 years) (Table 1). Twenty-two patients (68.75%) had chylothorax after a surgical intervention, seven patients (21.8%) had chylothorax due to medical causes and three patients (9.3%) after chest trauma. Thirty-eight percent of patients treated conservatively were after lung cancer resection and 35% of patients treated surgically where after esophageal resection. Chylothorax was stopped in 33% of patients after lymphangiography. Cumulative leak per day was 1007 ml/day for operated patients and 397 ml/day for patient treated conservatively. Esophageal resection surgery and the amount of fluid leak were the two factors founded to be associated for the decision of an earlier surgical treatment. Conclusion: Chylothorax arising after esophageal resection with a flow rate of leak of more than 500 ml/day should be proposed to an earlier surgical treatment. Lymphangiography remains a key stone assessment with a double aim diagnostic and therapeutic in chyle leakage.

Lamstatin – a novel inhibitor of lymphangiogenesis derived from collagen IV

The lymphatic system is essential for the maintenance of tissue homeostasis and immunity. Its dysfunction in disease (such as lymphangioleiomyomatosis) can lead to chylous effusions, oedema or dissemination of malignant cells. Collagen IV has six α chains, of which some of the non-collagenous-1 domains have endogenous anti-angiogenic properties, however, little is known about specific endogenous anti-lymphangiogenic characteristics. In this study we sought to investigate the expression levels of collagen IV non-collagenous-1 domains in lung tissue of patients with and without lymphangioleiomyomatosis to explore the hypothesis that a member of the collagen IV family, specifically the non-collagenous domain-1 of α5, which we named lamstatin, has anti-lymphangiogenic properties. Levels of lamstatin detected by immunohistochemistry were decreased in lungs of lymphangioleiomyomatosis patients. We produced recombinant lamstatin in an E.coli expression system and synthesized a 17-amino acid peptide from a theoretically identified, active region (CP17) and tested their effects in vitro and in vivo. Recombinant lamstatin and CP17 inhibited proliferation, migration and cord formation of human microvascular lung lymphatic endothelial cells, in vitro. Furthermore, lamstatin and CP17 decreased complexity and dysplasia of the tumour-associated lymphatic network in a lung adenocarcinoma xenograft mouse model. In this study we identified a novel, direct inhibitor of lymphangiogenesis, derived from collagen IV. This may prove useful for exploring new avenues of treatment for lymphangioleiomyomatosis and metastasis via the lymphatic system in general.

The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM)

Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on either transbronchial lung biopsy or video-assisted thoracic surgery, unless there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was recently considered as a novel diagnostic marker for LAM. Herein, we evaluated diagnostic value of serum VEGF-D in LAM patients. Serum samples were obtained from 78 cases of LAM (50 definite and 28 probable LAM based on European Respiratory Society guidelines), and 40 healthy female volunteers. VEGF-D was measured using enzyme-linked immunosorbant assay according to product instruction (R&D). Serum VEGF-D was significantly increased in definite LAM group, compared with that of health control (median: 3841.9pg/mL vs 405.5pg/mL respectively, p<0.001). The optimal cut-off point for definite LAM diagnosis was 850.7pg/mL. In probable LAM group, the majority of patients (92.9%) had serum VEGF-D level over 850.7pg/mL. The serum levels of VEGF-D in LAM patients with pulmonary cystic lesions only were lower than that in patients with any of evidences of AML, chylous effusions, adenopathy, lymphangioleiomyomas, or TSC, but higher than that in the health control. In addition, VEGF-D levels were correlated with disease severity measured as LAM CT grade, and presentations of chylous effusions and/or lymphatic involvement (p<0.05). Serum VEGF-D should be added to the current diagnosis algorithm to enhance definitive diagnosis for LAM.

A Case of Intestinal Lymphangiectasia, a Rare Cause of Protein Losing Enteropathy in a Non HIV Immunocompromised Patient

A 56 y/o Caucasian male with h/o psoriasis s/p etanercept 2 years ago was admitted with exertional sob and non-productive cough which got progressively worse for 2 weeks. Pertinent ROS including fever, night sweats, unintentional weight loss are negative. His social history is significant for 5 pack year smoking which he quit 18 years ago. Physical exam showed diminished breath sounds and dullness to percussion on the right side. He was found having right sided chylous pleural effusion. CT scan evaluation of the abdomen revealed marked thickening of the duodenum and proximal small bowel of which biopsy showed acute on chronic enteritis with focal granulomas positive for Mycobacterium Avium complex infection (MAC). He was found to be T cell deficient with CD4 count of 110 and the workup is negative for HIV and TB. He was started on Anti MAC therapy. Subsequently, he developed noninfectious diarrhea, further investigations revealed significant hypoalbunemia besides CT abdomen showing marked retroperitoneal and mesenteric adenopathy with diffuse infiltration surrounding the nodes. His hospital course was further complicated by recurrent pleural effusions, ascites and PJP pneumonia. Despite appropriate antibiotics and management including TPN with medium-chain triglyceride enriched low fat diet, patient's clinical condition deteriorated rapidly resulting in death. Pertinent Labs: wbc: 8.8; H&H: 9.8/29.3; platelets: 275; T. Bilirubin -0.3; AST: 44; ALT: 37; ALP: 202; Hepatits A, B&C are negative; Pleural fluid TG -190; HIV 1&2 NR Albumin 2.0; Total IgG 506. Discussion: Protein losing enteropathy (PLE) is defined as a condition in which excess protein loss into the gastrointestinal lumen, due to various causes, is severe enough to produce hypoproteinemia and hypoalbuminemia. Intestinal lymphangiectasia (IL) is a PLE caused by dilated lymphatic vessels in the intestinal wall due to obstruction of the lymphatics. It is usually seen in AIDS patients when they are infected with MAC involving the GI tract causing enteric protein loss. It was thought to be obstruction of the mesenteric and retroperitoneal lymphatics by MAC lymphadenitis resulting in PLE. Our patient is a non HIV immunocompromised presenting with Chylous effusion and PLE due to disseminated MAC Infection. It was presumed that he was infected during his prior treatment with etanercept for psoriasis and the etiology for his current immunosuppression remained elusive even after cessation of etanercept. Conclusion: This case adds impetus to the current literature for early recognition and management of intestinal lymphangiectasia, a rare cause of PLE in Non HIV immunocompromised patients.

Early Repair of Large Infant Ventricular Septal Defect Despite Respiratory Syncytial Virus–Induced Respiratory Failure With Postrepair Chylous Pericardial Effusion Requiring Pleuropericardial Window

The surgical correction of congenital cardiac lesions that are complicated by intercurrent respiratory syncytial virus (RSV) pneumonitis has traditionally been deferred for at least 6 to 8 weeks. The presumption is that using cardiopulmonary bypass will increase the risk of postoperative pulmonary complications. We present an infant who developed acute respiratory failure related to RSV pneumonitis and required urgent mechanical ventilation. Cardiac evaluation revealed a large nonrestrictive ventricular septal defect (VSD), aortic arch hypoplasia, normally functioning bicuspid aortic valve, and hemodynamic instability associated with markedly increased pulmonary blood flow. Separation from mechanical ventilation was unsuccessful preoperatively. He underwent VSD repair with cardiopulmonary bypass less than 4 weeks after initial RSV infection. He was extubated successfully within 72 hours of VSD repair. Approximately 6 weeks postoperatively, he developed a circumferential chylous pericardial effusion of unclear etiology--an exceedingly rare complication of VSD repair in early infancy in a non-Down syndrome patient. The chylous effusion was initially managed unsuccessfully with Portogen/Monogen and a percutaneously placed pericardial drain. Two weeks later, he underwent creation of a pleuropericardial window with successful resolution of the chylous effusion. It is of interest to pediatricians to be able to correctly time the repair of congenital heart disease lesions after RSV infection to minimize post-bypass pulmonary complications and yet avoid morbidity from undue delays in repair. In addition, chylopericardium can occur in infants after VSD repair, and dietary modification and catheter drainage may not be adequate.