conflict of interest of hideki kawanishi

Conflict of Interest of Hideki Kawanishi

I have/had an affiliation (financial or otherwise) with a pharmaceutical, medical device or communications organization. Honoraria of presentations by Terumo Corporation KISSEI PHARMACEUTICAL CO.,LTD Bayer Yakuhin Japan CO.,LTD

Tsuchiya General Hospital, Hiroshima, Japan

Hideki Kawanishi

International PD story

24 years experience of EPS surgery

ISPD, 2018 Vancouver

Prevalence and Mortality of EPS in survey

Study N EPS% /1000p

.y Death PDF

Multi-center

Retro

spective

EDTA, Oules 1988 0.03-0.31% 69% Acid

Japan, Nomoto 1996 6923 1.7% 44% Acid

Australia, Rigby 1998 7374 0.7% 1.8 56% Acid

Koria, Kim 2005 4249 0.8% 24% Acid

ANZDATA, 2010 7618 0.4% 1.8 54% Acid

Netherlands, Korte 2011 2022 2.7% 54% Acid+ico

Italy, Marinangeli 2012 4094 1.26% 7.0 42.9% Acid+Neut+ico

Scotland, Petrie 2016

Dutch EPS registry 2017

1238 2.8%

0.14

13.6 57.1%

48%

Acid

Pediatric Japan, Hoshii 2000 687 1.6% 27% Acid

EU, Shroff 2013 1472 1.5% 8.7 13.6% Acid+Neut+ico

Italy, Vidal 2013 712 1.9% 43% Acid+Neut+ico

Prospective Japan, Kawanishi 2004 1958 2.5% 3.18 38% Acid

Japan, Nakayama 2014 1338 1.0% 2.3 21.4% Neut+ico

Multicenter prospective observation study in Japan EPS study in, JAPAN Kawanishi H et al., AJKD 2004; 44:729-37

1999 – 2003, 1958 in 57center

PD duration:114.3±44.1, Acidic conventional PDF

EPS:48 (2.5%), 3.18/1,000py, after withdrawal PD 33 (68.8%)

Time on PD

< 3 years

3 to < 5 years

5 to < 8 years

8 to < 10 years

10 to 15 years

>= 15 years

Total

EPS cases (%)

0

4 (0.7%)

12 (2.1%)

14 (5.9%)

13 (5.8%)

5 (17.2%)

48 (2.5%)

Mortality (%)

-

0 (0%)

1 (8.3%)

4 (28.6%)

8 (61.5%)

5 (100%)

18 (37.5%)

≥10 years: incidence rate 7.1%,

mortality rate 72%

Acidic PDF

Multicenter prospective observation study in Japan EPS study in, JAPAN Kawanishi H et al., AJKD 2004; 44:729-37

The risk of EPS was high in patients on PD for 8 years or longer.

Acidic PDF

Acidic PDF

Acidic vs Neutral PDF in prospective observation study Acidic, Kawanishi

AJKD 2004

Neutral (NEXT-PD)

PDI 2014

Facility/patients 57/ 1958 55/ 1338

Follow 4ys 4ys

PD durations 114.3±44.1 67.3±18.8

EPS, /1,000 p.y 48 (2.5%), 3.18/1,000py 14 (1.0%), 2.3/1,000py

after withdrawal 33 (68.8%) 3 (21.4%)

EPS grade III I: 9, II: 4, III: 1

Recovery of

symptoms

non 11 (78.6%)

Mortality EPS related 37.5% all-cause 35.7%, EPS

related 21.4%

Neutral, Low GDP solution may be prevented EPS

EPS

Surgical Treatment for Encapsulating

Peritoneal Sclerosis: 24 Years’ Experience

”Submitted to PDI"

2008/7/1 Before After surgery

EPS Surgical case from 1993 to 2017 Cases 243, Total surgeries 318 times

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 year

Case

First surgery

Re-surgery

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

EPS Surgical case from 1993 to 2017 Cases 243, Total surgeries 318 times

year 1980

First EPS by PD

Gandhi VC

Arch Intern Med 1980

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS Surgical case from 1993 to 2017 Cases 243, Total surgeries 318 times

1980

First EPS by PD

Gandhi VC

EPS survey in Japan

AJKD 1996

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS Surgical case from 1993 to 2017 Cases 243, Total surgeries 318 times

1980

First EPS by PD

Gandhi VC

Consensus

meeting in Japan EPS survey in Japan

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

1980

First EPS by PD

Gandhi VC

Consensus

meeting in Japan EPS survey in Japan

ISPD Ad Hoc

Committee, Chicago,

December 10-11,

1998

ISPD Ad Hoc Committee, Chicago, December 10-11, 1998

PDI 2000; 20 suppl 4, S43-S55

Sclerosing encapsulating peritonitis (SEP)

Encapsulating peritoneal sclerosis (EPS)

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

1980

First EPS by PD

Gandhi VC

Consensus

meeting in Japan EPS survey in Japan

ISPD Ad Hoc

Committee, Chicago,

December 10-11,

1998

Prospective survey

AJKD 2004

AJKD2004

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

1980

First EPS by PD

Gandhi VC

Consensus

meeting in Japan EPS survey in Japan

ISPD Ad Hoc

Committee, Chicago,

December 10-11,

1998

Prospective survey

AJKD 2004

Encapsulating

Peritoneal

Sclerosis in Japan,

PDI2005

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

1980

First EPS by PD

Gandhi VC

Consensus

meeting in Japan EPS survey in Japan

ISPD Ad Hoc

Committee, Chicago,

December 10-11,

1998

Prospective survey

AJKD 2004

Encapsulating

Peritoneal

Sclerosis in Japan,

PDI2005

Definition of EPS

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

Prevention of EPS

～2000, Low GDF PDF

Lactate-Low GDP

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

Prevention of EPS

～2000, Low GDF PDF

Prospective survey of Low GDP

NEXT-PD, PDI 2014

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

My personal experience:

Small solute ⇒Large solute ⇒Low albumin

JSDT1993

Small solute

Large solute

sAlb

Three pore theory, Rippe B, Blood purif 1992

Small pore

Large pore

Increase of permeability of

Small solute

Large solute permeable

Protein permeable

Lower albuminemia

Bengt Rippe, pass away October 19 2016 1950-2016

3rd ACM-ISPD 2007

After 3 months, 1st EPS surgery, Oct/93

Three pore theory, Rippe B, Blood purif 1992

Small pore

Large pore

Increase of permeability of

Small solute

Large solute permeable

Protein permeable

Lower albuminemia

Increase Fibrin permeable

EPS

Inflammation

Surgery for EPS was contraindication in 1990’s

Most patients treated surgically died due to technical

complications. These deaths occurred by anastomosis failure

because the pathogenesis of EPS was not well understood by

surgeons, and, in many cases, simple resection of adherent

intestinal loops with enteroanastomosis was performed.

However, the final option for patients in whom bowel

obstruction symptoms fail to improve is surgical enterolysis,

0

5

10

15

20

25

30

35

40

93 94 95 96 97 98 99 2000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

year

EPS: Surgery

from 1993 to 2016, Twenty four years

Cases 236, Total surgeries 310 times

Presentation of EPS surgery

EPS surgery MAP

EPS surgery in Germany Latus J et al., NDT 2013; 28:1021-30

Severe (bowel obstruction) EPS 31 case to Surgical enterolysis.

Mortality 10 cases (32.2%) of 45.6 months

Post-op EPS: 4 case, Other 4 cases, Unknown 2 cases

Surgical cases

(Non-surgical)

EPS surgery in UK Campbell R, Augustine T et al., PDI 2014; doi:10.3747/pdi.2013.00098

Central Manchester University

2007-2010: EPS surgery 51 cases

Mortality 35%

Dutch EPS registry Betjes MH et al., PSI 2017; 37:230-242

2009-2015, EPS 53pts (post Tx 28.3%), 0.85%⇒0.14%

Treatment

Tamoxifen

Surgery

Prednisone

EPS surgery in Japan Japanese renal data registry (JRDR), end of 2015

Anamnestic history of EPS

Anamnesis of EPS

5.2%

Steroid therapy

86.5%

Surgery therapy

79.5%

yes yes

Clinical Practice GL PD in Adults and Children, The National Institute for Health and Care Excellence (NICE), June 2017

Guideline 7.2.1 – PD : Encapsulating Peritoneal Sclerosis: Management

• We recommend that patients with EPS should be referred or discussed

early with units who have expertise in EPS surgery. Surgery should be

performed by teams experienced in EPS surgery (GRADE 1B).

ISPD-GL

• It must be stated, though, that for surgical results to be successful, the

surgical team must have a thorough understanding of the pathology of

EPS. Such surgery should therefore only be done in specialist regional

centers that can provide appropriate surgical training and patient support.

Indication of surgery for EPS

Severe bowel obstruction: risk of bowel perforation

Malnutrition

Repeated obstruction symptoms

Jejunostomy Death

Time on PD 234 months

Scheme of EPS surgery

• Total enterolysis +

• Confirmation by Miller-Abbott’s Ileus tube

• Noble’s plications

Conventional

• +Jejuno-colostomy Sever obstruction

• Decompression by Percutaneous endoscopic gastrostomy (PEG)/PEG-J + home-TPN

Conservative

EPS surgery, Intestine cocooned

EPS surgery Peritoneal adhesions by repeated lysis of fibrin membranes

with a sharp instrument

EPS surgery Cut the fibrin membrane

EPS surgery Adhesiolysis of the mesenteric side is performed first, and

finally, encapsulated intestinal loops are lysed.

EPS surgery To identify the site of stenosis and/or injury part of intestine,

we have been inserting an Miller-Abbott’s ileus tube

balloon

EPS recurrent after surgery Probability of remaining EPS recurrence free

0

.2

.4

.6

.8

1 E

PS

rec

urr

ence

fre

e

0 20 40 60 80 100 120 140 160 180

Follow up (months)

1yr 22%

Enterolysis only:106

Recurrence:30 (28.3%)

Prevention of re-obstructive symptoms (recurrent)

Fixation of small bowel after adhesiotmy

Noble’s plication methods: Suture of small bowel

Noble TB, Am J Surgery 1937: 35, 41

KH, PD duration 115 m; Noble’s plication method

Treitz’s ligament

Ileum end

The prevents of passage disturbance and

escape into and adhesion in the pelvic

cavity

In the cases of risk of re-adhesion and/or Incomplete

enterolysis ; Side to side Jejuno-colostomy

Side to side Jejuno-colostomy

Incomplete enterolysis

Calcification

HK, PD duration 132 m

Side to side Jejuno-colostomy

EPS surgical video, HI, 2016/1/19

PD duration : 116 months, EPS caused by peritoneal sclerosis

EPS : 113 months after catheter, Operation : 12.8 months after EPS

Acidic ⇒ Neutral PDF

EPS surgical video, HI, 2016/1/19

PD duration : 116 months, EPS caused by peritoneal sclerosis

EPS : 113 months after catheter, Operation : 12.8 months after EPS

Acidic ⇒ Neutral PDF

石原

Survival of the EPS surgery, Cases 243, Total surgeries 318 times

1 2 3 5 8 years

Actuarial survival 91 83 77 66 53 %

Mortality EPS related death 5 10 13 20 28 %

Survival rates after diagnosis

0.0

0.2

0.4

0.6

0.8

1.0

0 24 48 72 96 120 144 168 192 216 240 264 288

Cu

mu

lati

ve

surv

ival

Time after diagnosis (months)

All cause death

EPS related death

Assessment of severity of intestinal damage The peritoneal calcification grade on CT

Grade 1<50% Grade 2 50-80% Grade 3 ≥80%

Grade 1 Grade 2 Grade 3

Assessment of severity of intestinal damage Degeneration/deterioration grade of small intestinal wall Grade 1: mild abnormal and soft; Grade 2: whole circumference/partial degeneration in several part, especially in the ileum; Grade 3: highly degenerated in almost all aria, Upper figure; before enterolysis, lower figure; after enterolysis

Kaplan-Maier survival analysis for assessment of severity of intestinal damage

Mortality curve for EPS-related death,

a) evaluation of peritoneal calcification grade (log rank test, grade 1 and 2, p<0.0015, grade 1 and

3, p<0.0065), G1:169, G2:27, G3:47

b) evaluation of degeneration grade of small intestinal wall, (log rank test, grade 1 and 2,

p<0.0452, grade 1 and 3, p<0.0008, grade 2 and 3 p<0.0058). G1:34, G2:163, G3:46

0

0.2

0.4

0.6

0.8

1.0

0 48 96 144 192 240 288 Time after diagnosis (months)

Peritoneal calcification, grade

Cu

mu

lati

ve

surv

ival

Grade 1

2 3

0 48 96 144 192 240 288 0

0.2

0.4

0.6

0.8

1.0

Time after diagnosis (months)

Degeneration of intestinal wall, grade

Cu

mu

lati

ve

surv

ival

Grade 1

2

3

Conclusion

EPS surgical experience and outcomes during 24 years in a

single center were reported; patients who undergo the

surgery showed better outcomes.

The increase in surgical treatment rate in the world promoted

improvements in countermeasures against and better

understanding of EPS.

Currently, EPS is no longer recognized as a fatal

complication.

Acknowledgment

Prof, Yoshindo Kawaguchi Prof Dimitrios Oreopoulos, Pass away April 2012

Prof Anders Tranæus, Pass away August 2015

EPS is no longer

recognized as a fatal complication.

Thank you for your attention