Injection therapy in the intervertebral disk by thecondoliase◆10:11:36

Meiryukai Akira Dezawa

1

PEL

SMED

固定PED

ヘルニコア

椎弓切除のみ

25

22

PEL

20

In our clinic

18

condoliase
17

16
15

19

17

19

17

16

15
14

14
13

12

12

12

11

11

10

10

9

9

9

9

9

8

8

10

9
8

8

FESS

7
6

66

5

54

44

4

4

300
2018年10月.

2

2

0
11月

12月

10:11:36

2

2019年1月.

2月

3月

4月

5月

6月

7月

8月

9月

10月

11月

12月

2020年1月.

2The cases of FESS surgery 15/180 (8.3%)◆The symptom was improved, but wantsto raise QOL more

Herniation combined with SCS◆ Overlook the lateral recess stenosis◆ Stimulate ganglion( POD )10:11:37◆Others◆

3cases211
8

Sub ligament

10:11:37transligament

By courtesy of Raushning10:11:37

5

Classification of tears of the intervertebral disc
Perinuclear tear

1Rim lesion
10% superior rim lesion
27% inferior

Radial tear3

2

Concentric tearcircumferential
fissures.

Longitudinal
fibers0:11:376

10:11:37

7

Collagen 10-25 laminar structure◆ Front side is thick、 rear is thin
◆ 30 inclination from a plane◆ most outer layer is Sharpey fibeｒ◆ depths touch it with the cartilage end plate◆Marginal injury

rimlayer

10:11:37

Weakening andtear of inner layer

innerlayer

Protrusion

protrusion9

delamination

10:11:37

10

Mechanism of cranial migration

L4

10:11:37

12

10:11:37

13

Intradiscal pressures.

healthyprone pos.

upright
stand.

uprightsitting

flex
stand

Mild
DiscDeg.

Moderate
DiscDeg.

SevereDisc
Deg.

Maximum
inflated pressures

Oblique pediculectomy to caudal migration
hidden zone approach

10:11:37

15

◆

history of the hernial disk extraction
1700

1919
◆ 1934◆ 1938
◆ 1932◆1977◆ 1970◆◆1977

Cotugno and Kocher
MacEwen, Krause, Taylor, Dandy, and Cushing, enchondroma
Goldthwaite
Mixter and BarrLove described the intralaminar, extradural approach.
Surgery of the assistant professor at Yoichi Azuma (Kyushu University)sciatica is
successful
Yasargil University of Zurich neurological surgery Father of the microsurgery
Weber and Hakelius, showed that many patients with lumbar disc herniation would
improve without surgical intervention.
Casper microdiscectomy

Transdural approach for herniation

history of the hernial disk extraction
1700◆ 1919◆ 1934
◆ 1938◆ 1932◆1977◆ 1970◆◆1977

Cotugno and KocherMacEwen, Krause, Taylor, Dandy, and Cushing, enchondroma
Goldthwaite
Mixter and BarrLove described the intralaminar, extradural approach.
Surgery of the assistant professor at Yoichi Azuma (Kyushu University)sciatica is
successful
Yasargil University of Zurich neurological surgery Father of the microsurgery
Weber and Hakelius, showed that many patients with lumbar disc herniation would
improve without surgical intervention.
Casper microdiscectomy

Automated Percutaneous Lumbar
Discectomy (APLD)

Automated percutaneous lumbar discectomy (also referred to as PercutaneousNuclectomy) was introduced by Gary Onik in 1985 as a means of providing a more safe
mechanical means of physically debulking the interior of a disc.
10:11:37

20

misTX of Lumbar surgery
MISS FUSION
Total arthroplasty

Discal arthroplasty
Nuclear arthroplasty
Dynamic stabilization(pedicle based)
Dynamic stabilization(facet /interspinous)
Endoscopic (Micro) discectomy

costComplication

risk

Percutaneous procedure

Molecular target therapy
Conservative TX

90%

aggression

sproutcradle

endoscopy lumbar spine surgery minimallyestablishmentseedtime

2005-2010
揺籃期、確率気

maturation

1995-2000

2000-2005

Laparolaparo thoraco MED

PELD-Full endo

182.176.172.184.187.188.189.192.193.

120.118.91.126.131.137.61.26.25

79.80.85.89.92.93.94.96.97.98.100.101.102.105.106.112.

29.18.16.31.35.36.37.42.48.53.55.56.60.65.76.77.78

前方 .210.237.238.207.208.212.214.215.216.
腰217.218.223.224.225.227.228.231.235.236

MED

2010-2015

194.195.196.198.199.200.203.204.205.206

150.152.159.160.166.179.1

113.116.121.122.130.132.137.140.143.145.147.148..

PE 230.229241
D
前方 213.209
胸pp
ts
revie
w
video etc

151.155.169.

82.83.84.86.87.88.104.110.111.114.117.119.123.

1.2.3.4.5.6.7.8.9.12.14.17.19.20.22.24.27.40.41.43.44.

124.125.129.133.135.136.141.142.

45.46.47.49.51.52.57.58.59.62.63.67.68.69.71.72.73.74

153.165.168.177.178.185.186.197.

99.90.81.103.127.134.139.146.

33.32.13.54.64

180.171157.23.1.30

183.161

0.115

11

190

138neuroscopy

21

109

34

95

66

144.128.107.149.156.158.162.163.167.170.50.28.70.75

micro
arthosco.232.222.219.234
pic
etc

202

Molecular target therapy
１）steroid injection therapy in the intervertebral disk（SIDT)２）Chemonucleolysis

10:11:37

23

Chymopapain(CP)1941◆ 1956◆ 1956◆ 1963◆ 1964◆ 1968◆ 1969◆ 1976◆ 1982◆ 1984◆ 1987◆ 2003◆Jansen Balls isolate it from the fruit of the papaya
Thomasbroken down cartilage cells with the CP in the ear of the rabbit
Feffersteroid injection therapy in the intervertebral disk （SIDT) JBJS
SmithInject CP in intervertebral disk of rabbits
Smith
Ten clinical outcomes
Yamagata
extract chondroitinase ABC from ProteusVulgaris
Sussmancollagenase(nucleolysin)
FDA
A double-blind study does not show efficacy
FDAApproval
Japanese IDT society
IITS(International Intradiscal Therapy Society)EUsuspend CP
10:11:37

Trasylol, hyaluronidase, ozone, keratanase24

Nerve conduction velocity(m/sec)◆Vehicle(n=6)

41-◆CondroitinaseABC (n=6) 53

ns◆

Chymopapain(n=3）

ｐ＜0.05

5

Olmarker Spine21:1996

Complications of CP(13500：1982-1991FDA)
0.5％Anaphylaxis (seven patients die 0.019%)◆ 24cases infection◆ 32
bleeding◆ 12paraplegia（ Problem of the needle tip side ）Haag(1999) late T8 myelopathy◆ Subarachnoid hemorrhage due to the dural injury◆ Cerebral hemorrhage
Clin Orthop Relat Res1993.122◆

Problems in adaptation and the procedure

27

The cases of FESS surgery 15/180 (8.3%)◆The symptom was improved, but wants
to raise QOL more

Herniation combined with SCS◆ Overlook the lateral recess stenosis◆ Stimulate ganglion( POD )10:11:37◆Others◆

3cases2
11
8

10:11:37

30

Condoliase patients in our clinic(2018,12-2020.3）

10:11:37

31

Cases at level
80

70.0%

70

60.0%

60
50.0%
50
40.0%

40
30.0%
30
20.0%
20

10.0%

100

0.0%

1.2
10:11:36

2.33.44.5cases

5.132

A grading system of intervertebral disk degeneration
Pfirmann

0337
140

Discogram type stage of disc degeneration
0◆

Cottonballno signs of degeneration soft white amorphous
nucleus◆Lobularmature disc with nucleus starting to coalesce
fibrous lumps◆

Irregular

degenerated disc with fissures and cleft in thenucleus and inner annulus◆

Fissureddegenerated disc with radial fissure leading toouter edge of annulus

45◆

Ruptured

Disc has a complete radial fissure that allow fluid toescape. can be any state of degeneration.

126

09

Annular tearwithout delamination

10:11:37

35

delamination

10:11:37

36

◆

◆

Posterior 4%

Anterior 33%

10:11:37

37

HIZ 6wbAprill C, Bogduk N : High- intensity zone : a diagnostic sign of painful lumbar disc on magnetic resonance imaging. Br J Radiol 65 : 361-369,
1992

38

Annular tear with delamination

10:11:37

39

Type of DiscoCT

Type1

2

3-1

3-2

Annular teardeg of nucleus
10:11:37

mild deg of annulus

severe deg of annulus
40

type1◎✖ type3-1

delamination

Type2Type２

Type3-1

10:11:37

43

Type 3-2

Clinical outcome of deg intervertebral disc
9.6%
8.0%

8.8%

8.0%
10.0%

6.4%
5.6%

9.0%
7.2%

4.8%
8.0%

4.8%
7.0%

5.6%

6.4%

6.0%

2.4%
4.0%

4.0%

4.8%

5.0%

1.6%

4.0%

3.2%

3/2fib

3.0%

2.0%

2.4%
1.6%

3/1fibrous

0.8%

2 nucleus
1.0%

1tear
0.0%

poor

no change

fair

good

excellentClinical results & history period

12.9%

11.8%
14.0%

10.8%

10.8%

12.0%
9.7%
8.6%

8.6%

10.0%

5.4%
8.0%
4.3%
6.5%

6.0%
2.2%

4.0%

3.2%
2.2%

2.0%

3（12M＜）2.2%2（6-12M）

1.1%

1（6M＞）
0.0%

123

4

5

Q1
Is a change of the disc height connected withdegeneration degree of the intervertebral
disk?
。

Disc height ratiob/aab

10:11:37

Three engineers measure three times and make the average48

Temporal changes of disc heightwith CT classification
105

100

100

96.6％

95

１
２
３－１
３－２

90
87.6
87.1

85

84.6

84.2
83.9
83.4

80

pre op.

1mos after op

3m after op

Mean age
25

JOA Recovery Ratio（％）

20％

others1010.237.3

others49.2

19.9

19.3

15

Annular tear

1mos

Annulcartear
90.6

average
87.6

3mos

83.4

84.2

7.6

50

Annular tear0pre op

1m sfter op

3m after op

p
0.113
0.104

Temporal changes of disc height with age

70gen

30gen

Q2
Did the difference of the clinicaloutcome result from a disc level?

JOA Recovery Ratio（％）

L5/1

L4/5

L5/S1

p

Preop.

12.6

14.9＊0.012

1mos

13.0

15.1

＊0.048

3mos

16.2

18.8

＊0.037

Change of disc height with leveｌs（％）
L4/5

1m
3mL5/1

L5/S1

88.3
86.2p87.6
0.123
80.4 ＊0.034

Case #30

44y female low back pain and leg pain for 2y
Adviser counselor◆

2018.112019.2◆ 2019.4.2◆ 2019.4.23◆ 2019.7.26◆

10:11:38

outpatient with sever lowback&leg pain
right s1 nerve root block effectcondoliase
return to work
complete recovery other than thedesensitization of the right leg

55

Case ＃３０

2019.4.20 condoliase

120

100

Leg pain80

Leg numbness

Buttock pain

60

40

20

Leg pain0

2018.11

10:11:36

2019.2

4.2

6.18

7.2656

✖ Transduralapproach○ transforaminalapproach10:11:38

59

Q3Is there the case to be improved remarkably
on the several days after a condoliase
injection?

4/180 CASES
10:11:38(1.4%)
61

Upper endplate
Low endplate

10:11:38

2019.4.2
Case30 FS
disappear in 1M 2019.2.13 5.27

7.22

Case #134
KY
remitted in a suppository
every day seven months
from the use infusion nextday

2019.6.18

2020.1.7
10.13
2020.1.15

case＃ 50
37y maleContinuous mig.

19.5.31Condoliase
19.4.919.9.28

20.2.12Mechanical effect◆① alkaline effect anti-inflammatory effect◆②cellular pain mediator◆③ polymerizing effect◆④ local control of autoimmune reaction

Q4．
How is the results of the case that disc heightdecreases rapidly?
A,The clinical outcome of the case to decrease rapidly of discheight is not good.
The case with disc height gradually decreases tends to havegood resultsChange of disc height

105

100

100

959085

rapid decrease(1M)

％

84.6

80

79.4

gradual dec

75

70

69.1

65

64.660pre oppost 3mpost 6mi

JOA Recovery Ratio（％）
25

22.3
20

rapid decrease1m

15

12.4

12.4

105.9
500

pre oppost op 1mos

post op 3mos

slow decreaseQ5 How Long Should You Wait Before Surgery?
The Timing FESS Surgery
グラフ タイトル

9.8%
14.6%

16.0%

14.6%

7.3%
14.0%
12.0%
9.8%
10.0%

2.4%

8.0%

3(16W<)
6.0%

2(4-16W

4.0%
2.0%

1(4w>)

0.0%

fair

goodexcellent

The cases of FESS surgery 15/180 (8.3%)

159.4days(23w)
period between condoliase inj. and FESS
15
1413
12
11
10
98
765432
1

10:11:36050

100

150200250300

The cases of FESS surgery 15/180 (8.3%)◆The symptom was improved, but wants
to raise QOL more

Herniation combined with SCS◆ Overlook the lateral recess stenosis◆ Stimulate ganglion( POD )10:11:38◆Others◆

3cases211
8

Hand down outside in

10:11:38

73

Inside -out

Q6
How much is the frequency of complications?

Complications 8/180(4.5%)
Eruption
5/180 (2.8%)
Pain of eyes
1/180 (0.6%)
出現/h

消失/d

2019/04/14

48

14

2019/07/23

48

7

2019/9/3

24

10

2019/10/11

48

10

2019/10/19

48

7

●

2019/12/01

48

7

●

2020/2/4

24

5OPE日

10:11:38

発熱

かゆみ腹痛

●頭痛発赤●

●

●

●

MRI画像

CTパターン

成績

不変

3-2

3

不変

3-25縮小

24

縮小

3-14

縮小

3-1

5

不変

3-24

不変

3-1

576

Case#115 MN 50y

2019.12.6 condoliase eye pain after inj

70

グラフ タイトル

60

12.6

50

40

30

20

100

8.4

lumbago
10:11:36

10.21

11.11

buttock p.

12.16

leg pain

1.15

l.numbness
77

Case#115 MN 50y
Eye pain

12.6
2019.5.4

2019.10.21

2020.1.15

グラフ タイトル

Case#96 eruption 36h after inj.

100

90

90

80

70

60

60

50

40

40

30

20

10

100

10:11:36

0lubago10・7

buttock pain 10.26leg pain 11月18日
numbness1月8日
10・21

79

Case#96 NN 44y１０・１９
2019.9.30 11.18 2020.1.8
eruption recoveredin 3mosL5/1

Case＃25 77y female
Pain & numbness of bilateral leg to havetrouble of for four years◆
L5 nerve root block was effective◆ 2019.4.14pm2
Condoliase was administrated◆ 4.15 midnight
exacerbation of low back pain at18h afteradministration of condoliase◆ 4.16
Eruption onset
Low back apina leg pain numness100/100◆2018 11

10:11:3881

グラフ タイトル

Case ＃25120

腰痛

臀部痛

下肢痛

下肢しびれ10080

Low back pain60Leg pain40

200
2018，11
10:11:36

2019,4,3

4.14

4月15日

4.17

4.24

6.19
82

Case no25 Erythema multiforme type：DLST(drug induced lymphocyte stimulation test (-)◆Case♯82 43f ganglion(POD)
VAS lumbago 80-90
Numbness50-100（ｒ－ｌ）
Leg pain10-100(r-l)

rs
10:11:38

84

By courtesy of RaushningNumber of endoscopic surgery
グラフ タイトル

In a nationwide survey over 100.000 MISS cases for decade
25000

20000

MED

PED

MEL

19942

15348

15000

14394
13731
13004
11154

10000

Total number7543
6239

5000

10962

10099

MED

6459

4611

MEL

PED02006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

4complications◆Dural tear

MEL>MED>cervical>PELD ・PEL
2.92

◆

SEH◆

Infections

Nerve injury

0.47 0.24

MEL ＞cervical ＞ MED ＞PELD ・PEL
0.48

◆

1.37

0.32

0.13

0.13

cervical >MEL>MED>PELD ・PEL

0.23

0.04

0.05

0.03

PELD ・PEL >cervical > MEL> MED
0.47

0.23

0.140.13

Guidelines on endoscopic lumber herniateddisc extraction

Indication◆ Clinical results◆ Complications◆ Invasiveness◆ Reherniation Prognosis
◆

L4/5

MED

Reherniation3y laterPELD

Reherniation open procedureRate of recurrence and the results
1．The endoscopic (MED, PELD) extraction ispossible for recurrent hernia. The results good ormore gain 90% of results from 81.4 in evaluation
criteria of Macnab.
2. There is a randomized, controlled comparison
report that the Chymopapain combination groupdecreased a recurrence from 6.9 in 1.9%. by thefollow-up of two years in the PELD method

Q8
DID YOU CONDUCT EFFECTMEASUREMENT OF THE CONDOLIASE
TREATMENT?
We examine the configuration of the nucleus pulposus
tissue after the condoliase exposure
We investigate whether the resolution of the chondroitin
sulfate was accomplished by a histopathological method
10:11:38

92

Diagram of the normal intervertebral disc structure

Nucleus pulposus
AFNPEPGPBM
Data on file at Seikagaku corporation

Annulus fibrosus

ER

Epiphyseal ring
Cartilaginous
endplate (thick)Growth plate
Bone marrow(trabecular bone)93

Case #37
63y female central herniation at L4/5level（Subligamentous extrusion）◆ Chief comp:leg pain low back pain
◆ Disease period: 15mos◆ administere the condoliase:2019/5/7◆ FESS surgery
2019/10/8◆( Clinical examination)◆ Modic: Type I◆ Disco CT: Type3-2（deg. Severe）◆ Disc height: no change◆ Leg pain
: Pain of lower extremities reappears in
1week after administration of condoliase
9419.3.6 （5/7）19.9.11 19.9.30
Case #37 63f

10:11:38

95

Method• Sample, human lumbar disc

• Staining - morphology
Hematoxylin and Eosin stain (H&E)
Safranin O stain (SO) Masson’s trichrome stain (MT)Toluidine blue stain (TB)
- confirmation of degradation of chondroitin sulfate
proteoglycans (CS-PGs) by HERNICORE
CS-PGs detection; antibody CS56
CS-PGs degradation product detection; antibody 2B6
Data on file at Seikagaku corporation

antibody 2B6◆

Monoclonal antibody 2B6 is produced using chondrotinase ABC digestive products of CSPGs as antigens, and recognizes the 4-sulfated unsaturated disaccharide neoepitope (⊿Di4S) which is a specific limited degradation cleavage surface (Stub).
:⊿CS; unsaturated disaccharide
neoepitope (⊿ Di-4S）

Intact chondroitin sulfate

CS56 : Intact(4S or 6S)

2B6(⊿ Di-4S)
Condoliase digestion

不飽和2糖構造（⊿Di-4S）

Data on file at Senkaku corporation97

10:11:38

99

10:11:38

100

10:11:38

101