Musculoskeletal embolization Inflammatory and degenerative Disease Yuji Okuno Musculoskeletal Intervention Center Edogawa Hospital Conflict of interest: none Tokyo, JAPAN J Vasc Interv Radiol 2013 June ; 24: 787-792 J Vasc Interv Radiol 2013 June ; 24: 787-792 • Tendinopathy and enthesopathy Lateral Epicondylitis (“Tennis Elbow”) Patellar Tendinopathy (“Jumpers’ Knee”) Achilles Tendinopathy etc Case: Patellar tendinopathy 58y.o. male High level long distance city runner 350km / month before disease onset Due to his pain, he could not run for 10 months Case: Patellar tendinopathy Patellar tendon Patellar tendon Affected side Unaffected side Selective angiography of lateral inferior genicular artery Before TAE Patellar Normal appearance of lateral inferior genicular artery Normal Knee patellar Selective angiography of lateral inferior genicular artery Before Embolization Patellar Selective angiography of lateral inferior genicular artery After Embolization Patellar Change of Pain Score Loxoprofen 180mg/day Physical Therapy Embolization 100 80 60 VAS (mm) VAS 40 20 Pain 0 2012 2013 2014 2016 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 7 （month） 1year follow up of first 12 patients with tendinopathy and enthesopathy Our MSK Embolization from 2012 to 2016 June • Tendinopathy and enthesopathy 98 cases • MSK shoulder pain (frozen shoulder etc) 128 cases • Knee osteoarthritis 95 cases • Sports injuries 44 cases • Persistent pain after joint replacement 32 cases • Others (hip, ankle, wrist, elbow, etc) 152cases total n = 549 Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Safety • Long term result • Required knowledge to start MSK embolization Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Safety • Long term result • Required knowledge to start MSK embolization How often abnormal vessels are visible in angiography? Prevalence of abnormal vessels Lateral epicondylitis (tennis elbow) Most common cause of chronic elbow pain and disorders 10% of these patients develop chronic symptoms and eventually require surgical intervention Prevalence of abnormal vessels 48 elbow in 43 patients Diagnosis made with 1. Clinical history of pain at lateral elbow 2. Physical findings (by elbow surgeon) Angiography & Embolization Normal appearance of elbow angiography Abnormal vessels in patients with tennis elbow Prevalence of abnormal vessels Abnormal vessels were visible n =48 in 48/48 elbows invisible 0 visible 48 Frozen shoulder ( Adhesuve Capsulitis ) • Characterized by painful restriction of shoulder motion. • Many refractory cases (35% had residual pain at seven years [1]) Normal shoulder Normal and abnormal findings of selective angiography of thoracoacromial artery Normal shoulder Frozen Shoulder J Should Elbow Surg. 2014 C : Coracoid H : Humeral Head Intact Direct branch from Axillary artery C H C : Coracoid H : Humeral Head Intact Direct branch from Axillary artery C H C : Coracoid H : Humeral Head Intact Direct branch from Axillary artery C H C : Coracoid H : Humeral Head Intact Direct branch from Axillary artery C H 50y.o. male C : Coracoid H : Humeral Head Frozen Shoulder Direct branch from Axillary artery C H 48y.o. female C : Coracoid H : Humeral Head Frozen Shoulder Direct branch from Axillary artery C H Prevalence of abnormal vessels 50 patients Diagnosis made with 1. Clinical history of pain at lateral elbow 2. Physical findings (by shoulder surgeon) n =50 invisible Abnormal vessels were visible 0 in 50/50 shoulders visible 50 Scientific background of Frozen shoulder • Hypervascularity in Frozen shoulder depicted by contrast enhanced MRI Song et al. AJR 2011 • Gondim Teixeira et al. AJR 2012 • Ahn et al. Clin Imaging 2015 Scientific background of Frozen shoulder • Increased neovessels in Frozen shoulder Observed during surgical procedure • Bunker et al. J Bone Joint Surg Br 1995 • Wiley et al. Arthroscopy 1991. • Yamaguchi et al. Arthroscopy 2002 Normal shoulder Frozen shoulder Scientific background of Frozen shoulder • Increased small vessels in Frozen shoulder Microscopic findings Hagiwara et al. Osteoar Cartilage 2012 • Bunker et al. J Bone Joint Surg Br 1995 • Xu et al. J Shoulder Elbow Surg 2012 Normal and abnormal finding of descending genicular artery Normal knee Mild radiographic knee OA a b Figure 1. Normal and abnormal vasculature of descending genicular artery MC, medial condyle; LC, lateral condyle. CVIR 2015 Prevalence of abnormal vessels Knee Osteoarthritis 72/75 cases =96% n =75 invisible 3 visible 72 Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Feasibility • Long term result • Required knowledge to start MSK embolization What type of embolic material should we use? Embolic Material Temporary Embolic particle • Imipenem/cilastatin sodium (IPM/CS) • Approved as an antibiotic • Compound slightly soluble to water • Forming small particle (diameter is 10-70 um) when we suspend with 5-10ml of contrast • Already in use as an embolic agent in Japan from 1990 - to stop intestinal tumor bleeding (oozing) due to its safety profile Woodhams et al. Springerplus. 2013 Temporary Embolic particle Aihara et al. Interv Radiol. 1999 Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Feasibility • Long term result • Required knowledge to start MSK embolization Short-term effect of Embolization • Frozen shoulder 48 cases Nighttime pain relief* were observed in 67% within 1 week 84% within 1 month after embolization *nighttime pain decreased more than 50% of baseline J Shoulder Elbow Surg 2014 JVIR under review Short-term effect of Embolization • Mild to moderate Knee OA 75cases Pain relief* were observed in 73% within 1 month 88% within 4 month after embolization *maximum pain decreased more than 50% of baseline CVIR 2015 KSSTA under review Short-term effect of Embolization • Tendinopathy and enthesopathy 98 cases Lateral Epicondylitis (“Tennis Elbow”) Patellar Tendinopathy (“Jumpers’ Knee”) Achilles Tendinopathy etc Pain relief* were observed in 76% within 3 months 84% within 6 months after embolization *maximum pain decreased more than 50% of baseline Why embolization of abnormal vessels relieve pain? • Improving inflammatory conditions (abnormal vessels maintain inflammation ) Mapp et al. Nat Rev Rheumatol. 2012 • Reducing stimulation from accompanying nerve fiber located close to small vessels (Nerve fiber grow around neovessels) Why embolization of abnormal vessels relieve pain? Control tissue Frozen shoulder Figure1 Microscopic findings of shoulder capsule tissue from frozen shoulder (right) compared with control tissue (left). Nerve fibers were often located close to increased small vessels in frozen shoulder tissue. Xu et al. J Should Elbow Surg. 2012 PGP 9.5 Nerve Fiber Blood vessel Why embolization of abnormal vessels relieve pain? Ljung et al 1999 J Orthop Res in Tennis elbow tissue • Pain-related nerve fiver located at near increased small vessels Histological study detecting increased vessels and accompanying nerve fiver • Tennis Elbow Sasaki et al. J Orthop Sci (2013) Ljung et al. Cells Tissue Organs (1999) Uchio et al. J Shoulder Elbow Surg (2002) • Achilles tendinitis Alfredson et al. KSSTA (2003) • patellar tendinitis Danielson et al. KSSTA (2008) • Frozen shoulder Xu et al. J Shoulder Elbow Surg (2012) • Knee Osteoarthritis Walsh et al. Osteoarthritis and Cartilage(2007) • Shoulder Rotator cuff tear Gotoh et al. J Orthop Res (1998) • Chronic low back pain Gronblad et al. Spine (1991) • Anterior knee pain Bohnsack et al. Arch Orthop Traum Surg (2005) • Temporomandibular disorder Yoshida et al. J Oral Rehabil (1999) Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Safety • Long term result • Required knowledge to start MSK embolization Safety Profile 「Phase 1/2 trial of MSK embolization for consecutive 100 patients 」 UMIN 000014591 Complications CTCAE Grade Number Pain during procedure 1 12 Puncture site hematoma 1 7 Radial artery spasm 1 5 Post procedure pain 1-2 4 vomiting (CE side effect) 1 1 Fever ( >38) 2 1 Peripheral paresthesia none Muscle weakness none Dermal necrosis / color change none How about using Microsphere? Small study using small sized (<100μm) microsphere for tendinopathy Change of pain score after embolization using small MS 7 days after Embolization using small-sized MS 7 days after Embolization 49 days afterEmbolization using small-sized MS using small-sized MS 7 days after Embolization 49 days after using small-sized MS Embolization using small- sized MS How about using Microsphere? Although it does work, but there is a risk of making ischemic conditions Today’s Contents • Prevalence of abnormal vessels in MSK disorders • Embolic material • Short term effect • Feasibility • Long term result • Required knowledge to start MSK embolization Long-term result of Embolization for Frozen shoulder JVIR under review Long-term result of Embolization for Knee Osteoarthritis KSSTA under review Pain recurrence? Pain Recurrence? Follow up survey Pain recurrence after your initial post embolization pain relief? n = 52 n = 46 Before 6months [PERCENTAGAfter E] 6months No No [PERCENTAG Recurrence recurrence E] [PERCENTAG 100% E] Frozen shoulder Tendinopathy and enthesopathy MRI Assessment at long-term follow-up MRI at 2 years after embolzation Before Embolization 2 years after Embolization KSSTA under review