Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy.

BACKGROUND: Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. SUBJECTIVE: The purpose of this study was to identify the potential lymph biomarkers for TIH. METHODS: Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. RESULTS: A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. CONCLUSIONS: This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Retrograde Transvenous Thoracic Duct Embolization for Tubercular Chylothorax.

This case study documents the clinical profile of a 27-year-old male patient who visited the medical facility two months ago with complaints of dry cough, fatigue, weight loss, and occasional fever. He had been treated for ascites and pleural effusion in the hospital before presentation and returned with an intercostal drain in place. A detailed examination revealed symptoms of respiratory disorders, including fluid in both lungs, fever, and dyspnea. His fluid levels showed multiple deviations from the normal range, according to the report's findings and lab test results. It was determined that the patient had chylothorax, which resulted from hemophagocytic lymphohistiocytosis (HLH) and abdominal tubercular lymphadenopathy. His anti-tubercular treatment (AKT4) was initiated, along with octreotide for his management. Initial management included non-invasive ventilator (NIV) support, intravenous antibiotics, nebulization, and an intercostal chest drain (ICD). Later, the patient underwent retrograde transvenous thoracic duct embolization (TDE) using N-butyl cyanoacrylate (NBCA) glue. The removal of the drainage tube and the patient's stable discharge were made possible through regular monitoring and collaboration between specialists.

Impact of Thoracic Duct Resection on Long-Term Survival After Esophagectomy: Individual Patient Data Meta-analysis.

BACKGROUND: Radical esophagectomy, including thoracic duct resection (TDR), has been proposed to improve regional lymphadenectomy and possibly reduce the risk of locoregional recurrence. However, because of its impact on immunoregulation, some authors have expressed concerns about its possible detrimental effect on long-term survival. The purpose of this review was to assess the influence of TDR on long-term survival. PATIENTS AND METHODS: PubMed, MEDLINE, Scopus, and Web of Science databases were searched through 15 March 2024. Overall survival (OS), cancer specific survival (CSS), and disease-free survival (DFS) were primary outcomes. Restricted mean survival time difference (RMSTD), risk ratio (RR), standardized mean difference (SMD), and 95% confidence intervals (CI) were used as pooled effect size measures. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology was employed to evaluate the certainty of evidence. RESULTS: The analysis included six studies with 5756 patients undergoing transthoracic esophagectomy. TDR was reported in 49.1%. Patients' ages ranged from 27 to 79 years and 86% were males. At 4-year follow-up, the multivariate meta-analysis showed similar results for the comparison noTDR versus TDR in term of OS [- 0.8 months, 95% confidence interval (CI) - 3.1, 1.3], CSS (0.1 months, 95% CI - 0.9, 1.2), and DFS (1.5 months, 95% CI - 2.6, 5.5). TDR was associated with a significantly higher number of harvested mediastinal lymph nodes (SMD 0.57, 95% CI 0.01-1.13) and higher risk of postoperative chylothorax (RR = 1.32; 95% CI 1.04-2.23). Anastomotic leak and pulmonary complications were comparable. CONCLUSIONS: TDR seems not to improve long-term OS, CSS, and DFS regardless of tumor stage. Routine TDR should not be routinely recommended during esophagectomy.

Lymphatic Interventions in Congenital Heart Disease.

Lymphatic disorders in congenital heart disease can be broadly classified into chest compartment, abdominal compartment, or multicompartment disorders. Heavily T2-weighted noninvasive lymphatic imaging (for anatomy) and invasive dynamic contrast magnetic resonance lymphangiography (for flow) have become the main diagnostic modalities of choice to identify the cause of lymphatic disorders. Selective lymphatic duct embolization (SLDE) has largely replaced total thoracic duct embolization as the main lymphatic therapeutic procedure. Recurrence of symptoms needing repeat interventions is more common in patients who underwent SLDE. Novel surgical and transcatheter thoracic duct decompression strategies are promising, but long-term follow-up is critical and eagerly awaited.

Thoracic duct drainage patterns in heterotaxy.

BACKGROUND: Disordered lymphatic drainage is common in congenital heart diseases (CHD), but thoracic duct (TD) drainage patterns in heterotaxy have not been described in detail. This study sought to describe terminal TD sidedness in heterotaxy and its associations with other anatomic variables. METHODS: This was a retrospective, single-center study of patients with heterotaxy who underwent cardiovascular magnetic resonance imaging at a single center between July 1, 2019 and May 15, 2023. Patients with (1) asplenia (right isomerism), (2) polysplenia (left isomerism) and (3) pulmonary/abdominal situs inversus (PASI) plus CHD were included. Terminal TD sidedness was described as left-sided, right-sided, or bilateral. RESULTS: Of 115 eligible patients, the terminal TD was visualized in 56 (49 %). The terminal TD was left-sided in 25 patients, right-sided in 29, and bilateral in two. On univariate analysis, terminal TD sidedness was associated with atrial situs (p = 0.006), abdominal situs (p = 0.042), type of heterotaxy (p = 0.036), the presence of pulmonary obstruction (p = 0.041), superior vena cava sidedness (p = 0.005), and arch sidedness (p < 0.001). On multivariable analysis, only superior vena cava and aortic arch sidedness were independently associated with terminal TD sidedness. CONCLUSIONS: Terminal TD sidedness is highly variable in patients with heterotaxy. Superior vena cava and arch sidedness are independently associated with terminal TD sidedness. Type of heterotaxy was not independently associated with terminal TD sidedness. This data improves the understanding of anatomic variation in patients with heterotaxy and may be useful for planning for lymphatic interventions.

Microsurgical central lymphatic reconstruction-the role of thoracic duct lymphovenous anastomoses at different anatomical levels.

Introduction: In recent years advances have been made in the microsurgical treatment of congenital or acquired central lymphatic lesions. While acquired lesions can result from any surgery or trauma of the central lymphatic system, congenital lymphatic lesions can have a variety of manifestations, ranging from singular thoracic duct abnormalities to complex multifocal malformations. Both conditions may cause recurrent chylous effusions and downstream lymphatic congestion depending on the anatomical location of the thoracic duct lesion and are associated with an increased mortality due to the permanent loss of protein and fluid. Methods: We present a case series of eleven patients undergoing central lymphatic reconstruction, consisting of one patient with a cervical iatrogenic thoracic duct lesion and eleven patients with different congenital thoracic duct lesions or thrombotic occlusions. Results: Anastomosis of the thoracic duct and a nearby vein was performed on different anatomical levels depending on the underlying central lymphatic pathology. Cervical (n = 4), thoracic (n = 1) or abdominal access (n = 5) was used for central lymphatic reconstruction with promising results. In 9 patients a postoperative benefit with varying degrees of symptom regression was reported. Conclusion: The presented case series illustrates the current rapid advances in the field of central microsurgical reconstruction of lymphatic lesions alongside the relevant literature.

VATS thoracic duct clipping in post-CABG with chylothorax.

Post-coronary artery bypass graft (CABG) surgery, chylothorax is a rare, but a serious, complication. We report a case of 49-year-old female who underwent CABG, and developed pleural effusion on post-operative day 2 which was milky in nature. Chylothorax was confirmed based on the biochemical analysis of the pleural fluid. As the medical line of management failed, video-assisted thoracoscopic surgery (VATS) was done and thoracic duct clipped on the right side. Close to the proximal portion of the left internal thoracic artery, disrupted tributaries of thoracic duct were noted and clipped. Rarity of the case and management is highlighted.

Lymphatic interventions in congenital heart disease.

Congenital heart disease affects 1/100 live births and is one of the most common congenital abnormalities. The relationship between congenital heart disease and lymphatic abnormalities and/or dysfunction is well documented and can be grossly divided into syndromic and non-syndromic etiologies. In patients with genetic syndromes (as examples listed above), there are known primary abnormal lymphatic development leading to a large pleiotropic manifestation of lymphatic dysfunction. Non-syndromic patients, or those without clear genetic etiologies for their lymphatic dysfunction, are often thought to be secondary to physiologic abnormalities as sequelae of congenital heart disease and palliative surgeries. Patients with congenital heart disease and lymphatic dysfunction have a wide variety of clinical manifestations for which there were not many therapeutic interventions available. The development of new imaging techniques allows us to understand better the pathophysiology of these problems and to develop different percutaneous interventions aiming to restore normal lymphatic function.

The supraclavicular approach to decompression of the thoracic outlet.

Surgical decompression of the thoracic outlet, along with treatment of the involved nerve or vessel, is the accepted treatment modality when indicated. Although neurogenic thoracic outlet syndrome (TOS) is often operated via the axillary approach and venous TOS via the paraclavicular approach, arterial TOS is almost always operated via the supraclavicular approach. The supraclavicular approach provides excellent access to the artery, brachial plexus, phrenic nerve, and the cervical and/or first ribs, along with any bony or fibrous or muscular abnormality that may be causing compression of the neurovascular structures. Even for neurogenic TOS, for which the axillary approach offers good cosmesis, the supraclavicular approach helps with adequate decompression while preserving the first rib. This approach may also be sufficient for thin patients with venous TOS. For arterial TOS, a supraclavicular incision usually suffices for excision of bony abnormality and repair of the subclavian artery.

Does Thoracic Duct Ligation at the Time of Esophagectomy Impact Long-Term Survival? An Individual Patient Data Meta-Analysis.

Background: Thoracic duct ligation (TDL) during esophagectomy has been proposed to reduce the risk of postoperative chylothorax. Because of its role in immunoregulation, some authors argued that it had an unfavorable TDL effect on survival. The aim of this study was to analyze the effect of TDL on overall survival (OS). Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched through December 2023. The primary outcome was 5-year OS. The restricted mean survival time difference (RMSTD), hazard ratios (HRs), and 95% confidence intervals (CI) were used as pooled effect size measures. The GRADE methodology was used to summarize the certainty of the evidence. Results: Five studies (3291 patients) were included. TDL was reported in 54% patients. The patients' age ranged from 49 to 69, 76% were males, and BMI ranged from 18 to 26. At the 5-year follow-up, the combined effect from the multivariate meta-analysis is -3.5 months (95% CI -6.1, -0.8) indicating that patients undergoing TDL lived 3.5 months less compared to those without TDL. TDL was associated with a significantly higher hazard for mortality at 12 months (HR 1.54, 95% CI 1.38-1.73), 24 months (HR 1.21, 95% CI 1.12-1.35), and 28 months (HR 1.14, 95% CI 1.02-1.28). TDL and noTDL seem comparable in terms of the postoperative risk for chylothorax (RR = 0.66; p = 0.35). Conclusions: In this study, concurrent TDL was associated with reduced 5-year OS after esophagectomy. This may suggest the need of a rigorous follow-up within the first two years of follow-up.

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.

Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial.

INTRODUCTION: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study's objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. METHODS: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. RESULTS: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). CONCLUSION: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.

Pitfalls in internal jugular vein cannulation.

Central venous catheter insertion in the internal jugular vein (IJV) is frequently performed in acute care settings, facilitated by its easy availability and increased use of ultrasound in healthcare settings. Despite the increased safety profile and insertion convenience, it has complications. Herein, we aim to inform readers about the existing literature on the plethora of complications with potentially disastrous consequences for patients undergoing IJV cannulation.

Thoracic duct identification with indocyanine green fluorescence to prevent chyle leaks during minimally invasive esophagectomy.

INTRODUCTION: Chylothorax (CT) is a rare yet serious complication after esophagectomy. Identification of the thoracic duct (TD) during esophagectomy is challenging due to its anatomical variation. Real-time identification of TD may help to prevent its injury. Near infra-red imaging with Indocyanine green (ICG) is a novel technique that recently has been used to overcome this issue. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer were divided into two groups with and without ICG. We injected ICG into bilateral superficial inguinal lymph nodes. Identification of TD and its injuries during the operation was evaluated and compared with the non-ICG group. RESULTS: Eighteen patients received ICG, and 18 patients underwent surgery without ICG. Each group had one (5.5%) TD ligation. In the ICG group injury was detected intraoperative, and ligation was done at the site of injury. In all cases, the entire thoracic course of TD was visualized intraoperatively after a mean time of 81.39 min from ICG injection to visualization. The Mean extra time for ICG injection was 11.94 min. In the ICG group, no patient suffered from CT. One patient in the non-ICG group developed CT after surgery that was managed conservatively. According to Fisher's exact test, there was no significant association between CT development and ICG use, possibly due to the small sample size. CONCLUSIONS: This study confirms that ICG administration into bilateral superficial inguinal lymph nodes can highlight the TD and reduce its damage during esophagectomy. It can be a standard method for the prevention of postoperative CT.

Fluorescence-guided thoracoscopic surgery for postoperative chylothorax: A technical note with video vignette.

TECHNIQUE: The surgical management for high-output postoperative chylothorax typically necessitates ligation of the thoracic duct (TD) above the leak site and/or sealing the leak with a clip. However, pinpointing these structures during subsequent surgeries can be challenging due to their variable course and the presence of traumatized tissues surrounding the leak area. In response to this, we have developed a novel, fluorescence-guided technique that significantly enhances intraoperative identification of the leak point and the TD. This method was applied in the case of a 52-year-old man suffering from refractory chylothorax following a previous lung cancer surgery. This study documents the surgical procedure and includes a video vignette for a comprehensive understanding. RESULTS: A bilateral inguinal lymph node injection of saline (10 mL), guided by ultrasound and containing 2.5 mg/mL indocyanine green (ICG), was administered 20 min prior to surgery. During thoracoscopic exploration, the leak point was precisely pinpointed in the right paratracheal area by transitioning from bright light to fluorescent mode. The TD was clearly identified, and upon ligation, there was no further leakage of fluorescent lymph, indicating a successful closure of the lymphatic structure. The surgery proceeded uneventfully, and the patient was able to resume oral intake on the third postoperative day. There was no evidence of recurring symptoms, leading to his discharge. CONCLUSION: The intralymphatic injection of ICG offers a rapid visualization of the TD's anatomy and can effectively pinpoint the leak point, even amidst traumatized tissues. Moreover, it provides prompt feedback on the efficacy of ligation.

Ultrasound analysis of cervical thoracic duct for patients with constrictive pericarditis and chylothorax.

PURPOSE: To analyze ultrasound features of cervical thoracic duct for patients with constrictive pericarditis and chylothorax. METHODS: Patients were retrospectively assessed. The patients were divided into a non-pleural effusion (PE) group (n = 54), a chylothorax group (n = 23), and non-chylothorax group (n = 28). Conventional ultrasound was used to obtain the maximum inner diameter and collapse of the inferior vena cava, the inner diameter of left cervical thoracic duct, and the frequency of opening of the valve at the end of the left thoracic duct. Contrast ultrasonography was used to score the reverse flow of the thoracic tube. RESULTS: The percentage of PE was 48.5%, and the percentage of chylothorax was 21.9%. The three groups had significant differences in five parameters. The inner diameter of left cervical thoracic duct was correlated with the degree of central venous pressure. Contrast ultrasonography was effective in quantitative assessment of the degree of intravenous-thoracic cord reverse flow which correlated with all parameters of central venous pressure. CONCLUSION: Thoracic duct dilation and regurgitation secondary to central venous pressure can lead to chyloreflux disorder and may be the mechanism of chylothorax occurrence in constrictive pericarditis.

Chylothorax Chronicles: Tubercular Lymphadenopathy and Hemophagocytic Lymphohistiocytosis.

Chylothorax delineates a state marked by the accumulation of chyle, an opalescent fluid laden with lipids, within the pleural cavity. This occurrence commonly ensues from the seepage of chyle originating from the thoracic duct, occasioned by trauma, surgical interventions, or underlying pathological conditions. This phenomenon induces respiratory distress, necessitating intricate and tailored interventions for its resolution. In this report, we present the case of a 27-year-old male who was admitted with a two-month history of symptoms, including dry cough, weakness, weight loss, and intermittent fever. Previously treated for pleural effusions and ascites, he was referred to our hospital with an intercostal drainage tube in place. Initial examinations revealed respiratory distress, fever, and bilateral pleural effusions. Laboratory results and fluid analysis indicated significant abnormalities, prompting further investigations, including CT scans and biopsies. The patient was diagnosed with chylothorax with chylous ascites due to abdominal tubular lymphadenopathy and hemophagocytic lymphohistiocytosis (HLH) and started on anti-tubercular therapy (AKT4) and octreotide. The patient was also initially managed with non-invasive ventilatory (NIV) support, intravenous antibiotics, nebulizations, an intercostal chest drain (ICD), and a thoracic duct embolization (TDE). Regular monitoring and collaboration between specialties were crucial, ultimately resulting in the removal of the drainage tube and the patient's stable discharge.

Laparoscopic transhiatal en-mass thoracic duct ligation for persistent bilateral spontaneous Chylothorax: A case report.

Chylothorax is a rare entity associated with morbidity. Surgical thoracic duct ligation (TDL) by thoracoscopic approach is the recommended choice for persistent chylothorax. However, thoracoscopy is not feasible in case of previous pleurodesis. We describe a successful laparoscopic transhiatal en-mass TDL in a 61-year-old lady for persistent spontaneous chylothorax after failed optimal conservative management and three sessions of pleurodesis. The study shows that laparoscopic transhiatal thoracic duct ligation is an effective alternative in a case where thoracoscopy is not feasible due to various reasons.

Retrograde transvenous thoracic duct embolization for lymphatic leakage after retroperitoneal tumor and lymph node resection: a case report and literature review.

BACKGROUND: Postoperative lymphatic leakage is a complication of ineffective conservative treatment for retroperitoneal mass. Herein, we report a case of lymphatic leakage that arose after retroperitoneal tumor resection and that was treated with retrograde transvenous thoracic duct embolization. CASE PRESENTATION: A 28-year-old man with persistent abdominal pain was diagnosed with a large retroperitoneal metastatic tumor measuring 10 cm and a subdiaphragmatic lymph node originating from a testicular tumor. After high orchidectomy and neoadjuvant chemotherapy, the subdiaphragmatic lymph node and retroperitoneal tumor were resected together with the abdominal aorta; the latter was reconstructed using a prosthetic graft. Postoperatively, the patient developed chylothorax. No improvement was observed after conservative treatment that included fasting and somatostatin therapy. The leakage site could not be identified using antegrade lymphangiography of the bilateral inguinal lymph nodes, but was detected using retrograde transvenous lymphangiography. The leakage site was successfully embolized. CONCLUSION: This case report describes successful treatment with retrograde transvenous thoracic duct embolization for chylothorax following resection of a retroperitoneal tumor and lymph node. This approach is a less invasive and more effective mode of treatment for chylothorax and should be considered before surgical thoracic duct ligation when the leakage point cannot be identified using the antegrade approach.