Pragmatic role of noncontrast magnetic resonance lymphangiography in postoperative chylothorax or cervical chylous leakage as a diagnostic and preprocedural planning tool.

OBJECTIVES: To define the roles of noncontrast magnetic resonance lymphangiography (MRL) in the management of postoperative chylothorax or cervical chylous leakage. METHODS: A total of 50 consecutive patients underwent noncontrast MRL, intranodal lymphangiography, and thoracic duct embolization between May 2016 and April 2020. Their mean age was 62.6 years ± 10.3 (SD) years, and 35 of the participants were men. Conventional lymphangiographic images were sufficient in quality as a reference for the evaluation of diagnostic accuracy of leakage and location in 35 patients (70%) and for evaluation of anatomic details of the thoracic duct and jugulovenous junction in 34 patients (68%). RESULTS: MRL showed that the sensitivity, specificity, and positive and negative predictive values for leakage detection were 100%, 97.1%, 100%, and 100%, respectively, and the concordance rate was 97.14% (95% confidence interval [CI], 85.08-99.93%; p < .001). Leakage location was concordant between MRL and conventional lymphangiography in 27 patients (77.1%, 27/35). Regarding anatomical details of the thoracic duct, variation of the thoracic duct was missed in 11.7% of patients (4/34). The jugulovenous junction was observed in 91.1% (31/34), and its opening into the central vein was depicted in 76.4% (26/34). The concordance rate was between 76.47 and 91.18. CONCLUSIONS: Noncontrast MRL has a high sensitivity for the detection of postoperative thoracic and cervical chylous leakage but is suboptimal for the localization of the leak and depiction of anatomical details of the thoracic duct. This method is worthy of consideration as either a decision-making or planning tool for subsequent interventions. KEY POINTS: • Noncontrast MRL provides limited resolution images of CLS but has a high sensitivity for the detection of postoperative chylous leakage in the thoracic and neck regions. • Noncontrast MRL is suboptimal for depicting anatomic details in the thoracic duct and jugulovenous junction but can play a role as a decision-making and a planning tool for subsequent lymphatic interventions.

Canine idiopathic chylothorax: Anatomic characterization of the pre- and postoperative thoracic duct using computed tomography lymphography.

Surgical treatment has improved the prognosis of canine idiopathic chylothorax, although a recurrence of the disease occurs occasionally after the procedure. An improved understanding of possible causes for this recurrence would be helpful for prognosis and treatment planning in affected patients. In this retrospective case series study, we described the detailed pre- and postoperative computed tomographic lymphography (CTLG) imaging characteristics for a group of dogs with surgically confirmed idiopathic chylothorax. Preoperative CTLG was performed in 12 of 14 dogs diagnosed with idiopathic chylothorax. Thoracic ducts were present on the right side in 10 dogs, left side in one dog, and bilaterally in one dog. All the 14 dogs received a combination therapy of pericardiectomy and thoracic duct ligation (TDL) by video-assisted thoracoscopic surgery. One week after surgery, a postoperative CTLG was performed, and the thoracic ducts were apparent in seven of 14 dogs. Three dogs had an unchanged course of the thoracic duct, which could have resulted from a missed duct. Four dogs were identified as having a bypass formation: the oblique duct originated at the ligation site and connected to the duct on the other side. Our findings indicated that one of the possible causes for postoperative recurrence of chylothorax in dogs could be "invisible or sleeping" fine ducts that are collapsed and not visible in preoperative CTLG scans. After TDL causes a change in the pressure of lymphatic flow, these fine thoracic ducts may become apparent using postoperative CTLG.

Hydrothorax in fetal cases of Opitz G/BBB diagnosis: Extending the phenotype?

We report two fetal cases carrying a de novo MID1 mutation and presenting with severe hydrothorax, suggesting the expansion of the phenotype of Opitz GBBB syndrome.

Dasatinib-induced Chylothorax in Chronic Myelogenous Leukemia in Pediatric Patient: Report of a Case and Review of Literature.

Dasatinib is a second-generation potent and efficacious oral tyrosine kinase inhibitor frequently used for imatinib-resistant or intolerant BCR-ABL-positive chronic myeloid leukemia and for Philadelphia chromosome-positive acute lymphocytic leukemia. Dasatinib is known to cause adverse pulmonary events such as chylothorax and has been described in the adult literature but not pediatric literature. The authors present a pediatric case of dasatinib-related chylothorax, subsequent management, and a review of the literature of adult cases with dasatinib-related chylothorax.

Computed tomographic lymphangiography via intra-metatarsal pad injection is feasible in dogs with chylothorax.

Lymphangiography can be useful for preoperative planning in chylothorax. Conventional ultrasound-guided intranodal injection can be difficult in some cases and is dependent upon operator skill. Alternative methods have been proposed to simplify the procedure, but their feasibility has not been sufficiently evaluated in clinical cases. The primary purpose of this multicenter, retrospective, descriptive study was to assess the feasibility and describe the clinical findings of CT lymphangiography by intrametatarsal pad injection in dogs with naturally occurring chylothorax. Twenty dogs were analyzed, and enhancement of thoracic ducts (TDs) was successful in 18 (90%) dogs within 5-14 min after initiating the injection, while successful enhancement of the lymphatic vessels cranial to the popliteal lymph nodes was seen in all dogs within 5 min after injection. The dose with good success to achieve TD enhancement was 1 mL/kg (concentration 350 mg I/kg). Only two dogs had mild discomfort after recovery from general anesthesia. Computed tomography lymphangiography by intrametatarsal pad injection is a feasible, easy, and safe procedure, which could provide adequate TD and cisterna chyli enhancement, identify TD number and cisterna chyli location and structure, and contribute to surgical planning.

Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43.

Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development. Mouse embryos with a null mutation in Cx43 (Gja1) were previously shown to completely lack mesenteric LVs at embryonic day 18. However, interpreting the phenotype of Cx43-/- mice was complicated by the fact that global deletion of Cx43 causes perinatal death due to heart defects during embryogenesis. We have now generated a mouse model (Cx43∆LEC) with a lymphatic-specific ablation of Cx43 and show that the absence of Cx43 in LECs causes a delay (rather than a complete block) in LV initiation, an increase in immature valves with incomplete leaflet elongation, a reduction in the total number of valves, and altered lymphatic capillary patterning. The physiological consequences of these lymphatic changes were leaky valves, insufficient lymph transport and reflux, and a high incidence of lethal chylothorax. These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs.

Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations.

Chylous pleural effusion (chylothorax) frequently accompanies lymphatic vessel malformations and other conditions with lymphatic defects. Although retrograde flow of chyle from the thoracic duct is considered a potential mechanism underlying chylothorax in patients and mouse models, the path chyle takes to reach the thoracic cavity is unclear. Herein, we use a novel transgenic mouse model, where doxycycline-induced overexpression of vascular endothelial growth factor (VEGF)-C was driven by the adipocyte-specific promoter adiponectin (ADN), to determine how chylothorax forms. Surprisingly, 100% of adult ADN-VEGF-C mice developed chylothorax within 7 days. Rapid, consistent appearance of chylothorax enabled us to examine the step-by-step development in otherwise normal adult mice. Dynamic imaging with a fluorescent tracer revealed that lymph in the thoracic duct of these mice could enter the thoracic cavity by retrograde flow into enlarged paravertebral lymphatics and subpleural lymphatic plexuses that had incompetent lymphatic valves. Pleural mesothelium overlying the lymphatic plexuses underwent exfoliation that increased during doxycycline exposure. Together, the findings indicate that chylothorax in ADN-VEGF-C mice results from retrograde flow of chyle from the thoracic duct into lymphatic tributaries with defective valves. Chyle extravasates from these plexuses and enters the thoracic cavity through exfoliated regions of the pleural mesothelium.

Risk Factors for Postoperative Chylothorax After Radical Subtotal Esophagectomy.

BACKGROUND: Chylothorax is one of the complications of esophagectomy for esophageal cancer. The treatment of this condition has been well discussed, but the risk factors for postoperative chylothorax remain unclear. METHODS: A retrospective review of 294 patients who underwent esophagectomy for esophageal cancer was conducted. These were patients with squamous cell carcinoma or adenocarcinoma of the esophagus including Siewert type I tumor of the esophagogastric junction who underwent subtotal esophagectomy with two-field or three-field lymphadenectomy. Of these, 24 patients who were diagnosed with chylothorax as a postoperative complication were allocated to the chylothorax group and the other 270 patients were allocated to the nonchylothorax group. RESULTS: Univariate analysis showed a significant difference in three factors: resection of thoracic duct, post-chemoradiotherapy, and high intraoperative fluid balance. Multivariate analysis revealed that post-chemoradiotherapy [hazard ratio (HR) = 3.430; 95% confidence interval (CI) 1.364-8.625] and high intraoperative fluid balance (HR = 1.569; 95% CI 1.2.7-2.039) were independent factors predicting chylothorax. In addition, resection of the thoracic duct may be a predictor of chylothorax after esophagectomy (HR = 3.389; 95% CI 0.941-12.201, p = 0.062). Receiver operating characteristic curve analysis of intraoperative fluid revealed that the sensitivity was 62.5%, specificity was 74.1%, and the cutoff value was 6.55 mL/kg/h. CONCLUSIONS: This study revealed that post-chemoradiotherapy and high intraoperative fluid balance are predictors of chylothorax after esophagectomy. The elucidation of clinicopathological factors that can predict the incidence of chylothorax will help to establish more effective perioperative management for esophageal cancer patients.

Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation.

Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation. This process, known as "lymphovenous hemostasis," is mediated by activation of platelet CLEC-2 receptors by the transmembrane ligand podoplanin expressed by lymphatic endothelial cells. Lymphovenous hemostasis is required for normal lymph flow, and mice deficient in lymphovenous hemostasis exhibit lymphedema and sometimes chylothorax phenotypes indicative of lymphatic insufficiency. Unexpectedly, the loss of lymph flow in these mice causes defects in maturation of collecting lymphatic vessels and lymphatic valve formation, uncovering an important role for fluid flow in driving endothelial cell signaling during development of collecting lymphatics. This article summarizes the current understanding of lymphovenous hemostasis and its effect on lymphatic vessel maturation and synthesizes the outstanding questions in the field, with relationship to human disease.

MEDIASTINAL LYMPHOMA AND CHYLOTHORAX IN A STRIPED SKUNK (MEPHITIS MEPHITIS).

Tumors are infrequently reported in skunks, with only a few case reports published in the literature. Chylothorax associated with mediastinal lymphoma was diagnosed in a captive 7-yr-old male striped skunk ( Mephitis mephitis ). The animal presented with anorexia and apathy. Supportive care and prednisolone improved the animal's clinical status for 2 wk preceding its death. Histopathology supported the clinical findings, and the tumor was classified as a mediastinal non-Hodgkin lymphoma, stage 2b, which has not been documented in the literature.

Non-Hodgkin lymphoma manifesting as massive malignant chylothorax: successful management with chemotherapy and ambulatory drainages using indwelling pleural catheter.

Recurrent cancer-related chylothorax is generally managed by talc pleurodesis or indwelling pleural catheter in the palliative care setting to relieve symptoms and improve quality of life. In chylothorax associated with curable/treatable malignancies like lymphoma, there are scarce data regarding the efficacy and safety of indwelling pleural catheters. We report a case of recurrent massive chylothorax associated with non-Hodgkin lymphoma who demonstrated long-term remission of lymphoma and complete regression of chylothorax after treatment with combination chemotherapy and ambulatory drainages using indwelling pleural catheter.

Chylothorax as a rare complication of acute pancreatitis in a 25-year-old woman after cesarean section.

The paper presents the case of a 25-year-old woman who underwent cesarean section for gynecological indications in the 37(th) week of her second pregnancy. The perioperative course was uncomplicated, but one day later the general condition of the patient suddenly deteriorated: she developed respiratory disorders requiring intubation and treatment in an intensive care unit. On the 6(th) day after the surgery, the patient was diagnosed with acute pancreatitis. Appropriate conservative treatment was instituted, resulting in a gradual improvement of her condition. On the 13(th) postoperative day, a cardiac arrest in asystole occurred, with no response to the undertaken resuscitation procedures. An autopsy performed in the Department of Forensic Medicine in Lódz revealed, among other findings, acute pancreatitis with enzymatic necrosis of the adipose tissue, a significant accumulation of lymph in both pleural cavities, and pulmonary atelectasis. As demonstrated by the analysis of the case, chylothorax had most probably developed in the course of acute pancreatitis which was a complication of the cesarean section. Consequently, the prosecutor opened an investigation into the case under Article 155 of the Polish Penal Code to assess the appropriateness of medical management. The medico-legal opinion was issued by experts from outside the Department of Forensic Medicine in Lódz. In their view, the medical management of the patient was correct.

Empyema caused by Prevotella bivia complicating an unusual case of spontaneous chylothorax.

Spontaneous chylothorax is rare in adults. We present an unusual case that was complicated by Prevotella bivia empyema. Full recovery was achieved with chest tube drainage and prompt treatment with intravenous clindamycin.

Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

[Nontraumatic chylopericardium and chylothorax in premature neonates].

Deaths of extremely premature babies undiagnosed as having spontaneous chylopericardium (CP) and chylothorax (CT) are analyzed. The specific features of these death cases are the polyetiology of CP/CT and the similarity of their pathogenesis in the absence of specific clinical symptomatology.

Morphological changes of the thoracic duct and accessory lymphatic channels in patients with chylothorax: detection with unenhanced magnetic resonance imaging.

OBJECTIVES: To characterise the imaging findings of patients with chylothorax and to identify the leak site using unenhanced MRI. METHODS: Seven patients with chylothorax and 30 healthy individuals (as the control group) underwent three-dimensional heavily and routine T2-weighted MRI. Morphological changes and diameters of the thoracic duct, chyloma display, and some dilated accessory lymph channels were evaluated and measured. The differences between patients and the control group were compared. The leak sites of the thoracic duct and parietal pleura were also identified. RESULTS: The patients had a higher display rate of the entire thoracic duct and some accessory lymphatic channels, enlarged diameters and tortuous configuration of the thoracic duct, and existence of chylomas compared with the control group (P < 0.05). Seven leaks of the thoracic duct in five patients and five leaks of the parietal pleura in four patients were identified. Close relationships between the leak of thoracic duct and the chylomas or the meshworks of tiny lymphatics were found (P < 0.05). CONCLUSION: Unenhanced MRI appears reliable in the detection of morphological changes of thoracic lymphatics and in the identification of chyloma and leak sites in patients with chylothorax, which helps appropriate treatment planning and follow-up.

Ultrasonographic characteristics of the cisterna chyli in eight dogs and four cats.

Ultrasonography of the cisterna chyli has been used in humans to diagnose increased lymphatic flow or lymph flow obstruction and to guide percutaneous embolization of the thoracic duct via the cisterna chyli. The aim of this study was to describe the ultrasonographic characteristics of the dorsal portion of cisterna chyli in dogs and cats with chylous ascites or chylothorax and in a group of healthy dogs and cats. The aorta and the cranial mesenteric artery were used as anatomic landmarks. Ultrasonography was performed before and 2 h after a fatty meal in healthy dogs and cats. The visualized structure was confirmed to be a dilated cisterna chyli at necropsy in a dog with chylous ascites. The confirmed or presumed cisterna chyli was consistently detected using ultrasonography in nonfasted healthy animals and clinically affected animals and appeared as an anechoic tubular structure, without detectable flow, at the right dorsolateral aspect of the aorta. It had a similar ultrasonographic appearance in patients with chyloabdomen and in nonfasted healthy dogs and cats. There was considerable overlap in diameters of the cisterna chyli for affected and healthy animals. The shape and size of the cisterna chyli in an individual animal were variable during the same ultrasound examination and between different examinations. This study demonstrated the appearance of the presumed dorsal portion of the cisterna chyli by ultrasonography and might provide useful preliminary data for further studies into the feasibility of ultrasound-guided injections or aspirations of the cisterna chyli in dogs and cats.

Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax.

Intraluminal valves are required for the proper function of lymphatic collecting vessels and large lymphatic trunks like the thoracic duct. Despite recent progress in the study of lymphvasculogenesis and lymphangiogenesis, the molecular mechanisms controlling the morphogenesis of lymphatic valves remain poorly understood. Here, we report that gap junction proteins, or connexins (Cxs), are required for lymphatic valvulogenesis. Cx37 and Cx43 are expressed early in mouse lymphatic development in the jugular lymph sacs, and later in development these Cxs become enriched and differentially expressed by lymphatic endothelial cells on the upstream and downstream sides of the valves. Specific deficiencies of Cx37 and Cx43 alone or in combination result in defective valve formation in lymphatic collecting vessels, lymphedema, and chylothorax. We also show that Cx37 regulates jugular lymph sac size and that both Cx37 and Cx43 are required for normal thoracic duct development, including valve formation. Another Cx family member, Cx47, whose human analog is mutated in some families with lymphedema, is also highly enriched in a subset of endothelial cells in lymphatic valves. Mechanistically, we present data from Foxc2-/- embryos suggesting that Cx37 may be a target of regulation by Foxc2, a transcription factor that is mutated in human lymphedema-distichiasis syndrome. These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man.