crohn's disase

Toru KonoDivision of Gastroenterologic and General Surgery Department of Surgery, Asahikawa Medical College

(Scenery from the window of my office)Mt. Taisetu National Park, Asahikawa,

Asahikawa (1 hour 40 min flight from Tokyo)

Tokyo

A new antimesenteric functional end to end hand-sewn anastomosis Surgical prevention of anastomotic recurrence in Crohn’s disease.

Diseases of the Colon & Rectum 2010

Kyoto

First International Consensus Conference on Kono-S anastomosis, Kyoto 2011

Autumn in Kyoto, Kinkakuji temple

Anastomotic recurrence and surgical recurrence of CD

(1993 to 2003)

5-year postoperative cumulative recurrence-free survival(ulcerative changes)

below 10% in historical CD cases

0

0.2

0.4

0.6

0.8

1

0 20 40 60 80 100 120 140 (mo)N=84

Cumulative recurrence-free survival (Kaplan-Meier analysis)

25% 6.4

50% 12.3

75% 38.6

5 years

> 90% recurrence within 5 years

Mean time to recurrence (mo.)

POP 11 months

Postoperative (POP) stenosis at anastomotic sitesPOP 40 months POP 52 months

5-year postoperative cumulative surgical recurrence increased to 26% in historical CD cases

0

0.2

0.4

0.6

0.8

1

0 20 40 60 80 100 120 140 (mo)

N=84

25% 56.850% 104.0

Cumulative surgical recurrence (Kaplan-Meier analysis) Mean time to reoperation (mo.)

Dept. Surgery

Asahikawa Medical University hospital

The S anastomosis technique was developed in 2003 at The S anastomosis technique was developed in 2003 at the Asahikawa Medical University Hospitalthe Asahikawa Medical University Hospital

Concept Concept •• Anastomotic recurrence site, which usually start Anastomotic recurrence site, which usually start

at at mesenteric sidemesenteric side of the anastomosing the ends of the anastomosing the ends of the remnant intestine. However, conventional of the remnant intestine. However, conventional anastomoses do not pay attention to this, anastomoses do not pay attention to this, besides the size of the anastomosis site. We besides the size of the anastomosis site. We designed an anastomotic technique to avoid the designed an anastomotic technique to avoid the stenosis at the anastomosing the ends of the stenosis at the anastomosing the ends of the remnant bowel by creating a remnant bowel by creating a supporting columnsupporting column, , like a stent. like a stent.

•• It is also important that the It is also important that the blood flow and blood flow and nervous systemnervous system should be preserved when a should be preserved when a resected intestine and its mesentery is divided, resected intestine and its mesentery is divided, because both are important factors for ulcer because both are important factors for ulcer healing and are etiologically abnormal in CD healing and are etiologically abnormal in CD intestine. intestine.

Normal ileum Crohn’s disease ileum

Red : nervous fiber and cell, Blue: DAPI indicate cell nucleus

SubmucosalSubmucosal nervous system is damaged due to nervous system is damaged due to repeated inflammation and can not fully recover repeated inflammation and can not fully recover

in Crohnin Crohn’’s diseases disease

CGRP

0

20

40

60

80

100

Control

CG

RP

( ng

/ g ti

ssue

wei

ght )

ADM

0.0

0.3

0.6

0.9

1.2

1.5

CD Model

AD

M (

ng /

g tis

sue

wei

ght )

Control CD Model

**

Selective loss of neuropeptide CGRP, but not ADM, in Crohn’s disease model and human

It has been reported that blood flow is decreased by more than 50% in the terminal ileum and colon of Crohn’s disease patients

Gastroenterology. 1977;72:388-96. Gut. 1986;27:542-9.

Ann N Y Acad Sci. 1992;657:319-27. Dig Dis. 2008;26:149-55.

Kono T. et al J Gastroenterology 2011 (in press)

Blood flow is decreased in Crohn’s disease because of depletion of neuronal peptide (CGRP), a potent vasodilatator, in human and animal models.

0 15 30 45 60 75 900.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14normal colonTNBS treated colon

min

CV

BloodFlow

Kono T. et al J Gastroenterology 2011 (in press)

CrohnCrohn’’s disease and intestinal s disease and intestinal blood flowblood flow

Slovenia

Blood flow is a very important factor in Blood flow is a very important factor in pathogenesis of Crohnpathogenesis of Crohn’’s diseases disease

IlealIleal ulcers tend to occur along the mesenteric margin of ulcers tend to occur along the mesenteric margin of the bowel wall in CD and experimental models of CDthe bowel wall in CD and experimental models of CD

J Clin Pathol. 1997;50:1013-7. Aliment Pharmacol Ther. 1999;13:531-5. Aliment Pharmacol Ther. 2000;14:241-5.

Florida Everglade

Mesenteric side

Crohn’s disease ileum

stenosis

Mesenteric sideMesenteric side

stenosis

Who can answer the prepotency of the Who can answer the prepotency of the CrohnCrohn’’s disease?s disease?Hypothesis: Hypothesis: Primary pathological abnormality in Primary pathological abnormality in CrohnCrohn’’s disease is in the mesenteric s disease is in the mesenteric blood supplyblood supply

Lancet. 1989;2:1057Lancet. 1989;2:1057--62.62.

long artery short artery

Schematic diagram of human small intestine in Crohn’s disease

Remission

Mesenteric margin

No connection between the submucosal plexuses derived from short artery and long artery

*

*

Blood flow CGRP

The association might well be explained in terms of granulomatous vasculitisaffecting small end-arteries that specifically supply the mesenteric margin

Mucosal barrier

bacteria

inflammation

granuloma

glanulomatousvasculitis

flora

Active

vessel

ulcer

Mesenteric margin

Normal

Lancet. 1989;2:1057Lancet. 1989;2:1057--62.62.

How to do KonoHow to do Kono--S anastomosisS anastomosis

Kyoto Darumaji

mesentery

ulcer stenosisTransectionof intestine

Intraoperative endoscopy

The whole bowel was inspected carefully for diseased segments using an endoscopic fiber via enterotomy at a nearby obvious stenosis site in all cases. Before resection of the diseased intestine, the surgeon and the gastroenterologist ensure by intraoperative endoscopy or direct observation there are no apparent mucosal lesions at the site of the intestine designated for anastomosis.

Intraoperative endoscopy

The nearby mesentery of the intestinal loop which is to be excised is divided using the LigaSure system (Valleylab) in order to avoid an unnecessary neurectomy as well as blood vessel dissection

diseased intestine

nerve fiberblood vessel

How to divide “mesentery”

diseased intestine

Nervefiber

blood vessel

diseased intestine

Nervefiber

blood vessel

diseased intestine

anastomosis

diseased intestine

anastomosisdiseased intestine

Resected area

Kono-S anastomosis: resection

Conventional anastomosis: resection

diseased intestineResected areaResected area

Diseasedintestine

Kono-S resection with LS Conventional resection with LS

腸間膜

Mesentericside

the intestine designated for anastomosis Diseased ileum

Diseased ileum

Multiple stenosis at ileum

specimen

the intestine designated for anastomosis

Linear stapler (LS)

How to make a “Supporting Column”

The reason : Both ends of the stump are reinforced with 3/0 Vicryl (Ethicon) , when a linear staple cutter is used.

End of the stump has a risk (leakage)for sealing with single stapling, therefore reinforcement is needed at the both ends.

3/0 Vicryl control-release

The reason : Both threads of the ends of stumps are firstly tied for adjusting some differences of the size of the stump, when a supporting column is made.

Both stumps are united with 3 or 4 threads.

Mesenteric side

relapsestarting pointat mesenteric side

Before anastomosis, both stumps are securely sutured in order to create a Supporting Column that can maintain the shape of the anastomosis The creation of a supporting column that maintains the shape of the anastomosis in order to prevent distortion due to relapse at the anastomotic site.

Supporting column“Supporting Column” avoids stenosis

Longitudinal enterotomy is performed in the antimesenteric side 1cm from the supporting column so as to obtain the optimal effect of the supporting column on the anastomosis, and the incision is opened across the intestinal longitudinal axis, resulting in a large anastomosis resembling the Heineke-Mikulicz type. The length of the opened incision across the longitudinal axis should be 7-8 cm, and it is closed to the length of the intestinal circumference.

Supporting column

Enterotomy

A side-to-side enteroenteric transverse anastomosis is performed by a handsewn, single-layer Gambee manner, using 3/0 Vicryl running sutures.

Resembles anastomosing the bottom ends of two flasks

Supporting column

Antimesenteric functional end to end hand-sewn anastomosis

Videotape on Kono-S anastomosis technique

34 years old. maleReoperation for anastomotic stenosis within 6 years of initial surgery

Ileocolic anastomosis + ileoileal anastomosis

Results of Kono-S anastomosis84 consecutive cases of intestinal resection for CD

from 2003 to 2010Asahikawa Medical University Hospital

S anastomosis at 107 sites

Ileal/jejunal: 44 Ileocolic: 57 Colonic: 6

Results of Kono-S anastomosis84 consecutive cases of intestinal resection for CD

from 2003 to 2010Asahikawa Medical University Hospital

S anastomosis at 107 sites

Ileal/jejunal: 44 Ileocolic: 57 Colonic: 6

Comparative analysis with 73 historical CD patients Comparative analysis with 73 historical CD patients who underwent conventional anastomoses who underwent conventional anastomoses

from 1993 to 2003from 1993 to 2003

a b

cd

A side-to-side S anastomosis A side-to-side conventional anastomosis

Functional end-to-end anastomosisAn end-to-end conventional anastomosis

Arrow and dotted line indicate the mesenteric side

Kono-S anastomosis and conventional anastomoses

Supporting column

Kono-S anastomosis (1 year)

Endoscopy

Endoscopic observation one year after Kono-S anastomosis

Analysis of endoscopic recurrence at the anastomosis after undergoing S anastomosis (Group S) or conventional anastomoses (Group C)

3.4

2.6

P=0.008

Comparison of surgical recurrence for anastomotic restenosis between S anastomoses and conventional anastomoses

0 12 24 36 48 60 72 84 96 108 120 1320

102030405060708090

100Group SGroup C

P = 0.0004

months

N = 84N = 73

Group C

Group S

0 12 24 36 48 60 72 84 96 10812013260

70

80

90

100

Time in Months

% p

atie

nts

rem

aini

ng fr

ee o

f sur

gica

l rec

urre

nce

Group S

Group C

n = 42Infliximab +

Infliximab +Infliximab -

Infliximab -

n = 42n = 12

n = 61

Logrank Test **p = 0.0006Logrank Test *p = 0.0041*, **

Surgical recurrence rates after undergoing an S anastomosis (Group S) or conventional anastomoses (Group C). With or without postoperative Infliximab

Group S combined with postoperative infliximab therapy (infliximab +), no infliximab (infliximab -), and Group C combined with postoperative infliximab therapy (infliximab +), no infliximab (infliximab -). Group S infliximab + vs. Group C infliximab -: P = 0.0041. Group S infliximab - vs. Group C infliximab -: P = 0.0006.

Comparison of anastomotic restenosis recurrence between S ansatomosis and conventional anastomoses

No postoperative administration of Infliximab/Adalimumab

0 12 24 36 48 60 72 84 96 108 120 13260

70

80

90

100

Group C

Group S

Logrank Test *p = 0.0045

n = 42

n = 61

Time in Months

Pisa

ConclusionConclusionKonoKono--S anastomosis, a new antimesenteric functional end to S anastomosis, a new antimesenteric functional end to end handend hand--sewn anastomosis, may be effective for preventing sewn anastomosis, may be effective for preventing postoperative anastomotic stenosis, even if infliximab postoperative anastomotic stenosis, even if infliximab postoperative therapy is not administered. postoperative therapy is not administered.