Volgograd State Medical UniversityVolgograd State Medical UniversityVolgograd, RussiaVolgograd, Russia

Experimental and clinical study of local cryoapplication in treatment of pancreatonecrosis

S. Maskin, L. Igolkina, V. Aleksandrov, S. Petrenko, A. Ntire, N. Ermolaeva, S. Кungurtsev, N. Loktev

Faculty of hospital surgery

Background:

local cryoapplication (LC) promotes primary interruption

of the pathological biochemical and morphological

changes cascade in the pancreas (P) and retroperitoneal

tissue, that leads to changes in the pathological process.

Objective:

is to asseses the results of applying of LC to P in different

forms of PN in experimental and clinical study.

Results of the experimental study

An experimental study was executed with Wistar rats.

The model PN was created by introduction of bile of 0,5 ml into P

All rats (157) were randomized in 2 groups

After CAn = 93

Without CAn = 64

Morphological and histological studies

were performed in 1-3, 5-7, 10-14 days

after first operation

Mortality in rats in both groups

Days after operation

aftercryoapplication

(n=93)

withoutcryoapplication

(n=64) p

n % n %

1-3 25 26,9 + 2,8 30 46,9 + 5,8 <0,001

5-7 2 2,2 + 0,2 11 17,2 + 2,1 <0,001

10-14 - - - - >0,05

Commonmortality

27 29,0 + 3,0 41 64,1 + 8,0 <0,001

p <0,001 <0,001

The mortality was statistically higher in the group WCA - 64% vs 29% in the group ACA.

These parities of parameters of mortality were registered in 1-3 and 5-7 days.

In the period over 10 days the mortality was absent in both groups

Behavioural actions in rats in both groups after operations

Behavioural actions

After cryoapplication (n=93)

Without cryoapplication (n=64) #

Days after operation Days after operation

1-3(n=93)

5-7(n=60)

10-12(n=8)

1-3(n=64)

5-7(n=34)

10-12(n=10)

no dynamics, weak mobility

9096,8+10,0

2135,0+4,4p1<0,001

112,5+4,6p1<0,001P5<0,001

64100

2779,4+13,6

*

330,0+9,8p1<0,001P5<0,05

refusal of food, weak reaction on food

8995,7+9,9

1830,0+3,8p1<0,001

-p1<0,001p5<0,001

64100

2676,5+13,1

*

220,0+6,5

*p1<0,05P5<0,05

decrease in reaction on painful irritation

8591,4+9,5

1321,7+2,7p1<0,001

-p1<0,001p5<0,001

5789,1+11,1

2058,8+10,1

*p1<0,05

220,0+6,5

*p1<0,001P5<0,01

* - p<0,01 - between groups # - p>0,05 - other parameters between groups

In the group WCA the dynamics of the recovery of the basic physiological actions was significantly slower. Positive dynamics were reliably defined only by 10th day. As for the other group, ACA the expressed positive dynamics were already confirmed by 5th-7th day, and by 10th day the complete recovery was acknowledged for almost all survived rats.

Моrphological and histological parameters in autopsy in rats of both groups (n / %)

* - p<0,01 - between groups ** - p<0,05 - between groups # - p>0,05 - other parameters between groups

Morphologicalparameters

After cryoapplication (n=93) #

Without cryoapplication (n=64)

Days after operation Days after operation

1-3(n=25)

5-7(n=60)

10-12(n=8)

1-3(n=30)

5-7(n=24)

10-12(n=10)

degree of collicvationnecroses of pancreas

1766,7+13,5

1423,3+2,9p1<0,001

- p1<0,001P5<0,001

2790,0+16,6

1145,8+9,4

**p1<0,05

220,0+6,5

**p1<0,001P5<0,05

pathomorphological variations in other organs (heart, luhgs, liver, intestines)

25100

2541,7+5,3p1<0,001

225,0+9,4p1<0,001P5<0,001

30100

1458,3+12,1

p1<0,05

550,0+16,5

p1<0,05P5>0,05

Activity of regeneration7

28,0+5,6

5185,0+10,8p1<0,001

787,5+33,5

p1>0,05p5>0,05

-*

520,8+4,2

*p1<0,001

660,0+19,8

p1<0,05P5<0,05

Total necrosis: kariolisis, citolisis, membranolisis

Local necrosis:

Day 2-3

x 64 x 160

x 64 x 160

without cryoapplication

Day 2-3

after cryoapplication

Day 5

x 64 x 64

x 64 x 160

without cryoapplication

Day 5

after cryoapplication

Subtotal diffuse necrosis

Local necrosis and normal pancreas:

Day 10-14

x 64 x 160

x 64 x 160

without cryoapplication

Day 10-14 after cryoapplication

diffuse necrosis

normal pancreas:

Conclusion of the experimental study

Local CA on a pancreas in PN

- leads to the fast regressing of the autolitic processes

- and to the early beginning of regenerative processes

in a pancreas,

- that allows to avoid the development of infected PN,

- To reduce the mortality - from 64 to 29 %

- and to accelerate restoration and clinical recover.

Results of the clinical study

All patients (208) were randomized in 2 groups

After CAn = 92

Without CAn = 116

Complications and mortality in the infected forms pancreatonecrosis

in both groups of patients

Formsof the

pancreato-necrosis

After cryoapplication (n=92) Without cryoapplication (n=116)

n

Complications(infected)

Mortality

n

Complications(infected)

Mortality

n % n % n % n %

Steril PN(n=17)

6 - - - - 11 645,5+14,1

**1

9,1+2,6*

Infected PN(n=197)

86 11 12,8+1,3 14 16,3+1,7 111х

(105+6)26

23,4+2,2 #

2926,1+2,5

*

Including: Infected PN with local PNPP (n=20)

14 - - - - 6 116,7+7,4

**1

16,7+7,4**

Infected PN with

total PNPP (n=177)72 11 15,3+1,8 14 19,5+2,2 105 25

23,8+2,3*

2826,7+2,6

**

In total (n=214) х 92 11 12,0+1,2 14 15,2+1,5 122х 3226,2+2,3

#30

24,6+2,2 ## - p<0,001 - between groups

* - p<0,01 - between groups** - p<0,05 - between groups

IPN - infected pancreatonecrosisPNPP – purulent necrotizing parapancreatitis

Mortality in the infected forms pancreatonecrosis

in both groups of patients

Groups of patients

After cryoapplication (n=92) Without cryoapplication (n=111)

Mortality - 14 (16,3+1,7 %) Mortality - 29 (26,1+2,5 %)

Formsof the

infectedpancreatonecrosis

IPN + local. PNPP

IPN + total. PNPP

including IPN + local. PNPP

IPN + total. PNPP

including

Initially PNPP

later

developed PNPP

Initially PNPP

later

developed PNPP

patientsабс. 14 72 61 11 6 105 79 26

% 16,3 83,7 70,9 12,8 5,4 94,6 75,2 24,8

mortality

абс. - 14 6 8 1 28 6 22

% -19,5+ 2,2

9,8+ 1,2

72,7+ 22,6

16,7+ 7,4 *

26,7+ 2,6 *

7,6+ 0,8 **

84,6+ 16,8 **

* - p<0,05 - between groups** - p>0,05 - between groups IPN - infected pancreatonecrosis

PNPP – purulent necrotizing parapancreatitis

Abdominal sepsis and mortalityin the infected forms pancreatonecrosis

in both groups of patients

Groups of patients

After cryoapplication (n=92) Without cryoapplication (n=111)

Mortality - 14 (16,3+1,7 %) Mortality - 29 (26,1+2,5 %)

Formsof the

infectedpancreatonecrosis

IPN + local. PNPP

(n= 14)

IPN + total. PNPP

(n = 72)

Including IPN + local. PNPP(n= 6)

IPN + total. PNPP

(n = 105)

Including

Initially PNPP

(n = 61)

later

developed

PNPP (n = 11)

Initially PNPP

(n = 79)

later

developed PNPP(n = 26)

sepsis

n - 10 2 8 - 25 4 21

% -13,9+ 1,6

3,3+ 0,4

72,7+ 22,6

-23,8

+ 2,3 *5,1

+ 0,5 *80,8

+ 10,1**

mortality

n - 4 - 4 - 17 - 17

% -40,0

+ 13,2-

50,0+ 19,0

-68,0

+ 13,8 **-

81,0+ 17,9**

* - p<0,001 - between groups** - p>0,05 - between groups

IPN - infected pancreatonecrosisPNPP – purulent necrotizing parapancreatitis

The number of arrosive hemorrhages

decreased due to the local CA in infected PN

- 1,1+0,6% vs 3,6+0,3% (p<0,001)

Modification of methods local cryoinfluence on a pancreas – introduction of liquid nitrogen in bursa omentalis

We carry out anatomical and experimental studies

The procedure becomes simpler, including the laparoscopyapproach.

Currently, in collaboration

with Russian Innovative company

BIOMEDSTANDART CJSC,

we are conducting works

on development and creation

of cryosurgical equipment and tools

for these purposes.

Conclusion

Performed experimental and clinical studies suggest high

efficiency of local CA for treatment of different forms of PN.

The obtained clinical data confirm pathogenetic validity of

CA for the treatment of different forms of PN,

that leads to the decrease of purulent-necrotic complications

in P and parapancreatic tissue and to the decrease

of mortality of this severe pathology.

Volgograd State Medical UniversityVolgograd State Medical UniversityVolgograd, RussiaVolgograd, Russia

Thank you for your

attention!

Faculty of hospital surgery