Director of HUP/CHOP Center for Lymphatic Imaging and Interventions

Transcription

1 Introduction Lymphatic Interventions: The Real Next Frontier Associate Professor of Radiology and Pediatrics Maxim Itkin MD, FSIR Director of HUP/CHOP Center for Lymphatic Imaging and Interventions

2 Physiology Lymphatic System-Structure Reverse tree Trunk Thoracic duct Branches are 3 Lymphatic Systems Peripheral Lymphatic System Liver Intestine

3 Physiology Lymphatic System-Flows Reverse tree Trunk Thoracic duct 100% Branches are 3 Lymphatic Systems Peripheral Lymphatic System Liver Intestine Liver 40% 20% 40% Intestine Lumbar, extremities, soft tissue

4 Lymphatic Flow Diagram Physiology

5 Background Background/History Central lymphatic flow physiology was extensively studied in up to the 1970 s. 40 years of Hiatus! Absence of lymphatic imaging methods Absence of interventional techniques

6 Traditional Lymph Flow Imaging Techniques Imaging PEDAL LYMPHANGIOGRAM PEDAL LYMPHOSCINTIGRAPHY

7 Imaging Lymphatic Vessels Imaging Intranodal Lymphangiogram Facilitate Interventions Contrast Enhanced MR Lymphangiogram Diagnosis Nadolski GJ, Itkin M.. J Vasc Interv Radiol. 2012;23: Dori Y, Zviman MM, Itkin M. Radiology Nov;273(2):410 6.

8 Imaging Intranodal Lymphangiogram G spinal needle Extension tubing 3ml polycarbonate syringe Nadolski GJ, Itkin M. Feasibility of ultrasound-guided intranodal lymphangiogram for thoracic duct embolization. J Vasc Interv Radiol. 2012

9 Intranodal Lymphangiogram Imaging Nadolski GJ, Itkin M.. J Vasc Interv Radiol. 2012;23:

10 Imaging Shunt to Vein Kariya S, Komemushi A, Nakatani M, et al. Intranodal lymphangiogram: technical aspects and findings. Cardiovasc Intervent Radiol 2014;37:

11 Imaging Intranodal Lymphangiogram Upstream Access

12 Imaging Intranodal Lymphangiogram Upstream Access TD

13 Imaging Contrast Enhanced MR Lymphangiogram Intranodal injection Combined MR and Fluoroscopy Machine XMR >150 cases performed Dori Y, Zviman MM, Itkin M. Dynamic Contrast-enhanced MR Lymphangiography: Feasibility Study in Swine. Radiology Nov;273(2):410 6.

14 MR Lymphangiogram Imaging

15 MR Lymphangiogram Imaging Idiopathic Chylothorax

16 Embolization Thoracic Duct Embolization Constantine Cope first described minimally invasive lymphatic intervention Cope C. Percutaneous thoracic duct cannulation: feasibility study in swine. J Vasc Interv Radiol. 1995;6:

17 Therapeutic Approaches to Lymphatic Flow Disorders Chylothorax Lymphatic Embolization Plastic Bronchitis Pulmonary Lymphangiomatosis Chylous Ascities Liver Lymphatic Embolization Ascities Protein Loosing Enteropathy Liver Lymphorea Thoracic Duct Externalization Congenital Lymphodysplasia

18 Embolization Thoracic Duct Embolization Treat Chylothorax Minimally invasive alternative to Thoracic Duct Ligation Rational Lymphangiogram identification of the leak Minimally invasive less mortality, morbidity

19 Intranodal Lymphangiogram Embolization

20 Intranodal Lymphangiogram

21 Embolization Thoracic Duct Access Access duct as soon as you see contrast Peripheral duct Fast stubbing movement Can go through everything Cisterna Chyli

22 TD Injection Embolization

23 Embolization Embolization Microcoils Nester Liquid embolic agent Glue -n-butyl Cyanoacrylate (n-bca)

24 Coil Deployment Embolization

25 Glue injection Embolization

26 Embolization Traumatic Chylothorax Clinical Success The overall (intent to treat) success rate was 77/109(71%) The overall success-attempted interventions 77/88 (88%) Itkin et al JTCVS 2010

27 Embolization Traumatic Chylothorax Clinical Success-Intranodal Lymphangiogram 55 adult patients over the last two years 53/55 (96%) successfully treated with TDE Overall >400 cases 60 cases post unsuccessful TD ligation 89% success of embolization after failed TD ligation Nadolski et al SIR 2016 Nadolski et al CIRSE 2016

28 Pulmonary Lymphatic Perfusion Syndrome Pulmonary Lymphatic Perfusion Syndrome (PLPS) TD Flow Components 100% 40% 40% 20%

29 Pulmonary Lymphatic Perfusion Syndrome (PLPS)-aka Lymphatic Reflux Pulmonary Lymphatic Perfusion Syndrome

30 Pulmonary Lymphatic Perfusion Syndrome Pulmonary Lymphatic Perfusion Syndrome Congenital Lymphatic Variant Plastic Bronchitis Pulmonary Lymphangiomatosis Non-traumatic Chylothorax

31 Pulmonary Lymphatic Perfusion Syndrome Plastic Bronchitis Formation of large gelatinous or rigid branching airway casts

32 Pulmonary Lymphatic Perfusion Syndrome Contrast Enhanced MR Lymphangiogram Perfusion of the Right Hilum Dori Y, Keller MS, Rome JJ, et al. Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease. Circulation 2016;133:

33 Pulmonary Lymphatic Perfusion Syndrome Thoracic Duct Injection Dori Y, Keller MS, Rychik J, Itkin M. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient. Pediatrics. 2014

34 Plastic Bronchitis

35 Bronchoscopy TD Injection Methylene Blue Plastic Bronchitis Pulmonary Lymphatic Perfusion Syndrome

36 Pulmonary Lymphatic Perfusion Syndrome Embolization-Lipiodol Dori Y, Keller MS, Rychik J, Itkin M. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient. Pediatrics. 2014

37 Pulmonary Lymphatic Perfusion Syndrome Plastic Bronchitis Embolization-Outcome 18 Patients with PB 16 demonstrated pulmonary lymphatic perfusion 15/16(94%) significant improvement of their symptoms (Dori et al. Circulation 2016)

38 PB Anatomic Categories Type 1 Type 2 Type 3 Type 4 Type 5 (Dori et al. Circulation 2016)

39 Lymphatic Anomaly Kaposiform Lymphangiomatosis Presentation 2014 March 2015 on Sirolimus

40 Lymphatic Anomaly Kaposiform Lymphangiomatosis

41 Lymphatic Anomaly Kaposiform Lymphangiomatosis Pulmonary Lymphatic Perfusion Syndrome

42 Lymphatic Anomaly Kaposiform Lymphangiomatosis Pulmonary Lymphatic Perfusion Syndrome

43 Follow up 07/ /2015

44 Pulmonary Lymphatic Perfusion Syndrome Neonatal chylothorax Gray M, Kovatis KZ, Stuart T, Enlow E, Itkin M, Keller MS, et al. Treatment of congenital pulmonary lymphangiectasia usingethiodized oil lymphangiography. Journal of Perinatologyp; 2014 Sep 1;34(9):720 2.

45 Pulmonary Lymphatic Perfusion Syndrome Pulmonary Lymphatic Perfusion Syndrome Congenital Lymphatic Variant Plastic Bronchitis Pulmonary Lymphangiomatosis Non-Traumatic Chylothorax Possible Effects 5-10% of Population CHF Chronic Bronchitis Interstitial Lung Disease Bronchopulmonary Dysplasia

46 Liver Lymphangiogram and Embolization Liver Lymphatic System Ernst Starling (1894) First described liiver lymphagiogram flow Normal liver lymph contributes 30-40% of the flow to the TD Estimate ml/day 40% of total body proteins returned to blood circulation through TD

47 Liver Lymphangiogram and Embolization Liver Congestion Congested liver (cirrhosis, CHF) Flow increases 10 folds liters a day in adult Original theory of liver ascities Leakage of the lymph in the peritoneal cavity Dumont AE, Witte MH. Significance of excess lymph in the thoracic duct in patients with hepatic cirrhosis. Am J Surg Witte MH, Dumont AE, et al. Lymph circulation in congestive heart failure: effect of external thoracic duct drainage. Circulation 1969 Jun

48 Liver Lymphangiogram and Embolization Liver Lymphangiogram First described in 1962 Moreno et al Few publications Curiosity (Clain 1968, Ocuda 1976) Investigation of portal hypertension (Moreno 1963) Hepatic Lymphorea (Matsumoto 2000) Lymph nodes metastasis (Teramoto 2002)

49 Liver Lymphangiogram and Embolization Penn/CHOP Experience Liver Lymphorea Ascities Protein Loosing Enteropathy (PLE)

50 Liver Lymphangiogram and Embolization Hepatic Lymphorea 56-year-old male History of hepatitis Whipple procedure Postoperativly large volume ascities Denver Shunt failed Guez D, et al. J Vasc Interv Radiol Jan;25(1):

51 Liver Lymphangiogram Liver Lymphangiogram and Embolization

52 Embolization with Onyx Liver Lymphangiogram and Embolization

53 Liver Lymphangiogram and Embolization Outcome One paracenthesis day after the procedure-cured from ascities US showed periportal thickening Guez D, et al. J Vasc Interv Radiol Jan;25(1):

54 Liver Lymphangiogram CHF ascities Ascities in Right Side CHF 60 YO Tricuspid valve insufficiency (repaired) Developed severe ascites few months after surgery Not clear chylous

55 Liver Lymphangiogram Liver Lymphangiogram CHF Ascities

56 Liver Lymphangiogram Liver Lymphangiogram CHF Ascities

57 Liver Lymphangiogram CHF Ascities Outcome Significant improvement of the ascites Prior to procedure twice a week After 14 days one parenthesis (3 liters) Five months later recurrence of the symptoms Repeat lymphangiogram

58 Liver Lymphangiogram

59 Liver Lymphatic Embolization Contrast Injection Glue Injection

60 Outcome No paracenthesis since the procedure 5 months

61 Liver Lymphangiogram PLE Protein Loosing Enteropathy Severe loss of serum proteins into the intestine

62 Liver Lymphangiogram PLE PLE Pathophysiology Concept Physiology : Liver generates albumin and delivers it into blood stream through lymphatic system Liver lymph high concentration of proteins The lymphatic flow in liver increases significantly in patients with CHF Hypothesis: The loss of the albumin in PLE happens from the liver lymph leaking into the intestine

63 Liver Lymphangiogram PLE PLE Treatment Concept Perform liver lymphangiogram If leak attempt to embolize

64 Liver Lymphangiogram PLE Liver Lymphangiogram PLE Contrast in duodenum

65 Liver Lymphangiogram PLE Intraprocedure Endoscopy Injection of the methylene blue into liver lymphatic ducts

66 PLE

67 Initial Experience Four patients with congenital cardiac disease-severe PLE First 2lipiodol embolization, Last 2 n-bca glue embolization Outcome Three patients temporary improvement of the albumin and significant improvement of symptoms First two patients duodenal bleeding after lipiodol injection Lipiodol crossing mucosa, can potentially cause irritation of the mucosa and bleeding Last two patients no lipidol injection into lymphatic ducts-no complications

68 Outcome Patient 1 (lipiodol) Patient 3 (1:6 diluted glue) Liver Lymphangiogram PLE

69 Liver Lymphangiogram PLE

70 Liver Lymphangiogram PLE Outcome Patient 4 (1:2 diluted glue) Albumin blood level /2/15 12/3/15 12/4/15 12/5/15 12/6/15 12/7/15 12/8/15 12/9/15 12/10/15 12/11/15 12/12/15 12/13/15 Series1 12/14/15 12/15/15 12/16/15 12/17/15 12/18/15 12/19/15 12/20/15 12/21/15 12/22/15

71 Follow up/bone Scan for PLE Three weeks latter albumin dropped to 1.5 Most of the symptoms recur

72 Second Procedure

73 Bone Scan for PLE

74 Follow Up Of Second Procedure 7 days Albumin All symptoms (ascites, edema, diarrhea) disappeared

75 PLE Treatment Future Loss of the albumin happen due to leakage of liver lymph into intestine Need to achieve more sustainable response More extensive embolization Magnetic navigation technology Ablation of duodenal mucosa leakage points using laser ablation technology

76 Achievements Where we are today 1. Treatment of Chylothorax 100% success rate in treatment of traumatic chylothorax % success rate in treatment of non traumatic chylothorax 2. Discovered etiology and developed treatment for Plastic Bronchitis 94% success 3. Discovered etiology and developed treatment for Neonatal Chylothorax 4. Discovered etiology and developed treatment for Protein Loosing Enteropathy 5. Discovered etiology and conceptualized treatment Pulmonary Lymphangiomatosis 6. Successful treatment of Chylous Ascities

77 Future Future MRL and Lymphatic Embolization Liver Lymphatic Embolization Chronic Bronchitis Interstitial Lung Disease Bronchopulmonary Dysplasia Cardiac Ascities Liver Cirrhosis Ascities Congenital Lymphodysplasia Thoracic Duct Externalization HIV Immunotherapy (car T cell) T cell depletion therapy

78 Future Future MRL and Lymphatic Embolization Liver Lymphatic Embolization Chronic Bronchitis Interstitial Lung Disease Bronchopulmonary Dysplasia Cardiac Ascities Liver Cirrhosis Ascities Congenital Lymphodysplasia Thoracic Duct Externalization HIV Immunotherapy (car T cell) T cell depletion therapy

79 Future Future Development of the new lymphatic imaging agents Liver lymphatic Imaging Intestinal Lymphatic Imaging Development of the new treatment of the CHF Pulmonary Perfusion Syndrome Development of the Lymphatic Pump

80 Team Team Max Itkin Interventional Radiology (CHOP/HUP) Yoav Dori Interventional Cardiology(CHOP) Gregory Nadolski Interventional Radiology (HUP)