Triveneta – Udine, Aprile 2006

Il problema della definizione delle complicanze in chirurgia

pancreatica

Prof. Claudio Bassi MD

Surgical and Gastroenterological Department

UNIVERSITY of VERONA

claudio.bassi@univr.it

The Anastomotic Leak (alias “spiffero”!) in pancreatic surgery is the underlining

phenomena of

Pancreatic fistula

Peripancreatic collections

Peripancreatic abscess

DGE

Bleeding

Pancreatic Fistula… DO WE SPEAK THE SAME

LENGUAGE?

Bassi C., Butturini G., Molinari E., Mascetta G., Salvia R., Falconi M., Gumbs

A. and Pederzoli P.

Pancreatic fistula rate after pancreatic resection. The

importance of definitions.

Dig Surg 21:54-59,2004.

Post-operative Pancreatic Fistula

A Medline search of the last 10 years.

A score was assigned to the reproducible definitions.

Post-operative Pancreatic Fistula

The Medline search of the last 10 years identified 26 different definitions.

14/26 definitions were found suitable for the applied score.

Score SystemScore Output (cc/day) Timing *

1 >100 >11

2 >50 8-10

3 >25 4-7

4 >10 >4

* The sum between starting day and P.F.duration

Four final definitions summarizing the current pancreatic fistula concept according to the

literature. 

D1: Output more than 10cc/day of amylase rich fluid since 4th p.o day or for more than 4 days. (Score 7)

D2: Output more than 10cc/day of amylase rich fluid since 8th p.o day or for more than 8 days. (Score 6)

D3: Output between 25 cc/day and 100cc/day of amylase rich fluid since 4th p.o day or for more than 4 days. (Score 5 and 4)

D4: Output more than 50 cc/day of amylase rich fluid since 11th p.o day or for more than 11 days. (Score 3)

Post-operative Pancreatic Fistula

The 4 definitions were applied to 242 pancreatic head resections with P-J carried out from 1997 to 2000 in our Institution.

The Chi-Square test Yates correct test was than applied (p<0.05).

Incidence of pancreatic fistula in 242 patients using four different definitions

  Definition

P.F. .

D1: Output more than 10cc/day of amylase rich fluid since 5th p.o day or for more than 5 days. 

69 (28.5%)

D2: Output more than 10cc/day of amylase rich fluid since 8th p.o day or for more than 8 days. 

44 (18.5%)

D3: Output between 25 cc/day and 100cc/day of amylase rich fluid since 4th p.o day or for more than 4 days.

40 (16.5%)

D4: Output more than 50 cc/day of amylase rich fluid since 11the p.o day or for more than 11 days. 

24 (9.9%)

 

WE NEED A “GENTLEMAN

AGREEMENT” AMONG PANCREATIC SURGEONS!

upon an objective and internationally accepted

definition to allow comparison of different surgical

experiences!

POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS DEFINITIONMembers of the International Study Group on

Pancreatic Fistula Definition: Claudio Bassi (Verona, Italy), Christos Dervenis (Athens, Greece), Abe Fingerhut (Poissy, France), Charles Yeo (Baltimore, USA), John Neoptolemos MD (Liverpool, UK), Masayuki Imamura (Kyoto, Japan), Michael Sarr (Rochester, USA), William Traverso (Seattle, USA), Marcus Buchler (Heidelberg, Germany), Keith Lillemoe (Indianapolis, USA), Carlos Fernandez de Castillo (Boston, USA), Laureano Fernanadez Cruz (Barcelona, Spain), Clem Imrie (Glasgow, UK), Roland Andersson (Lund, Sweden), Dirk Gouma (Amsterdam, Netherland), Milicevic Miroslav (Belgrade, Yugoslavia), Andren Ake Sandberg (Gothemburg, Sweden), Tadahiro Takada (Tokio, Japan), Valerio Di Carlo (Milan, Italy), Josè Eduardo Cunha (San Paulo, Brasil), Rob Petbury (Adelaide, Australia), Helmut Friess (Heidelberg, Germany), Krzysztof Bielecki (Warsaw, Poland), Efthimios Chatzitheoklitos (Thessaloniki, Greece), Gregor Tsiotos (Athens, Greece), Colin Johnson (Southampton, UK), Mike Mac Mahon (Leeds, UK), Attila Olah (Gyor, Hungary), Tibor Tihani (Budapest, Hungary), Robin Williamson (London, UK), Jakob Izibicki (Hamburg, Germany), Giovanni Butturini (Verona, Italy), Roberto Salvia (Verona, Italy), Nora Sartori (Verona, Italy), Massimo Falconi (Verona, Italy), Paolo Pederzoli (Verona, Italy).

POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS

DEFINITION Surgery 2005;138:8

A general definition of pancreatic fistula is an abnormal communication between the pancreatic ductal epithelium and another epithelial surface containing pancreas – derived, enzyme - rich fluid. However POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or it may represent a parenchymal leak not directly related to an anastomosis such as one originating from the raw pancreatic surface, e.g. left or central pancreatectomy, enucleation, and/or trauma. In this case there is a leak from the pancreatic ductal system into and around the pancreas and not necessarily to another epithelialized surface, e.g. a surgical drain.

POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS

DEFINITION Suspicion and diagnosis

The diagnosis of POPF may be suspected based on the many clinical or biochemical findings. A broad definition begins with the following criteria: output via an operatively-placed drain (or a subsequently placed, percutaneous drain) of any measurable volume of drain fluid with amylase content greater than three times the upper normal serum value.

Drain fluid could have a “sinister appearance” that may vary from dark brown, to greenish bilious fluid, to milky water, to clear “spring water” that looks - like pancreatic juice. Associated clinical findings may include abdominal pain and distention with impaired bowel function, delayed gastric emptying, and fever > 38oC. Serum WBC > 10.000 cells/mm3 and increased C – reactive protein may also be present.

Radiologic documentation is neither mandatory nor necessarily recommended for diagnosis. However imaging may be useful by identifying erosion or migration of the drain into an enteric viscus and thus need for drain withdrawal to allow healing of the site of erosion.

“sinister appearance? … no!”take it out as soon as possible!!

“sinister appearance? …yes!”look to amylase content!

“sinister appearance? …yes!”look to amylase and bacteria

content!

POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS

DEFINITION Suspicion and diagnosis

The diagnosis of POPF may be suspected based on the many clinical or biochemical findings. A broad definition begins with the following criteria: output via an operatively-placed drain (or a subsequently placed, percutaneous drain) of any measurable volume of drain fluid with amylase content greater than three times the upper normal serum value.

Drain fluid could have a “sinister appearance” that may vary from dark brown, to greenish bilious fluid, to milky water, to clear “spring water” that looks - like pancreatic juice. Associated clinical findings may include abdominal pain and distention with impaired bowel function, delayed gastric emptying, and fever > 38oC. Serum WBC > 10.000 cells/mm3 and increased C – reactive protein may also be present.

Radiologic documentation is neither mandatory nor necessarily recommended for diagnosis. However imaging may be useful by identifying erosion or migration of the drain into an enteric viscus and thus need for drain withdrawal to allow healing of the site of erosion.

Pancreatic fistula

Role of imaging useful by identifying erosion or migration of the

drain

POPF GRADING SYSTEM Surgery

2005;138:8 GRADE A B C

Clincal Conditions

Well Often well Ill appearing

or bad

Specific treatment

No Yes/No Yes

US/CT Negative Neg//Pos Positive

Drain after 3 weeks

No Usually yes Yes

Reoperation

No No Yes

Death No No Possibly yes

Signs of Infections

No Yes Yes

Sepsis No No Yes

Readmission

No Yes/No Yes/No

Grade A Fistulas

10 Criteria are utilized to establish each grade

Elevated Drain Amylase Readmission

Persistent Drainage Critical Condition

Signs of Infection Re-operation

Diagnostic Imaging Sepsis

Specific Treatments Death

Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8-Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8-13.13.

Grade B Fistulas

10 Criteria are utilized to establish each grade

Elevated Drain Amylase Readmission

Persistent Drainage Critical Condition

Signs of Infection Re-operation

Diagnostic Imaging Sepsis

Specific Treatments Death

Modified by Pratt et al. fromModified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8-Bassi C et al. Surgery 2005; 138: 8-13.13.

Grade C Fistulas

10 Criteria are utilized to establish each grade

Elevated Drain Amylase Readmission

Persistent Drainage Critical Condition

Signs of Infection Re-operation

Diagnostic Imaging Sepsis

Specific Treatments Death

Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8-Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8-13.13.

International Study Group on Pancreatic Fistula Definition

CONSENSUS DEFINITIONConclusion 1

Only after clinical recovery is complete it is possible to ultimately distinguish and to grade the POPF as Grades A, B and C with respect to the clinical impact.

International Study Group on Pancreatic Fistula Definition

CONSENSUS DEFINITIONConclusion 2

The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when addressing new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders.

Clinical and Economic Validationof the

International Study Group on Pancreatic Fistula

Classification Scheme

Wande PrattShishir K. MaithelTsafrir Vanounou

Zhen HuangMark P. Callery

Charles M. Vollmer, Jr.

Department of SurgeryBeth Israel Deaconess Medical Center

Harvard Medical School

Doris Duke Charitable Foundation

Clinical Validation on 176 Whipple

Clinically-Relevant Parameters

Hospital stay (LOS and readmission)

Postoperative complications

Costs

Hospital Stay

8 813

35

0

10

20

30

40

Days (median)

No Fistula Grade A Grade B Grade C

ISGPF Grade

p < .001

Complications

37%

12%

76%

100%

0%

20%

40%

60%

80%

100%

Rate

No Fistula Grade A Grade B Grade C

ISGPF Grade

p = .20

p < .05

Total Hospital Costs

$18.855 $18.075

$25.158

$113.150

$0

$20.000

$40.000

$60.000

$80.000

$100.000

$120.000

Costs

(median)

No Fistula Grade A Grade B Grade C

ISGPF Grade

p < .001

Summary

ISGPF Classification Scheme Grade A Fistulas are clinically insignificant Only Grade B and C fistulas are clinically significant

Clinical and Economic Validation Increasing fistula severity impacts outcomes

A New Sub-Classification - ISGPF Scheme Amylase-Rich vs. Amylase-Deficient Fistulas

Still “open” problem …

Does the drain fluid amylase contain reflect pancreatic leakege?

WE NEED INTERNATIONAL SHARING OF DATA …

PRELIMINARY DATA FROM ONE SINGLE CENTRE

137 Evaluated Resections: No POPF VS POPF

resezioni

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

gg

resez complicate

resezioni regolari

resez complicate 19873,185212116,2593 8326,037047119,925934159,9259314531,7391 24852,4615

resezioni regolari 3043,544551061,55446 318,405941 108,3 64,40625 76,440678 71,3333333

ams 1sx ams 2 sx ams3sx ams 4sx ams 5 sx ams 7sx ams 9sx

PD: No POPF VS POPF

dcp

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

gg

dcp regolari

dcp fi stole

dcp decubito

dcp regolari 2870,115385 999,5064935 299,2987013 98,88311688 53,44 80,86538462 71,33333333

dcp fi stole 16483,93333 7953,733333 6511,933333 4128,8 3393,8 21894,78571 30290

dcp decubito 1504,375 1347,625 585,25 205,875 355,125 1138,428571 2669,4

ams 1sx ams 2 sx ams3sx ams 4sx ams 5 sx ams 7sx ams 9sx

Left Pancreatctomy: No POPF VS POPF

resezioni

0

5000

10000

15000

20000

25000

gg

distali regolari

distali complicate

distali regolari 3486,20833 1260,625 379,708333 139,826087103,571429 43,5714286 0

distali complicate 24026,4167 17319,4167 10593,6667 10858,83335117,58333 3078,11111 6727,33333

ams 1sx ams 2 sx ams3sx ams 4sx ams 5 sx ams 7sx ams 9sx

2741 300 1 12800 20 1 13200 100 1 1

120 1 1640 1 1

3261 50 1 13300 120 1 13424 32 1 13470 83 1 13915 20 1 14141 40 1 14373 20 1 14470 200 1 15000 50 1 1

490 1 15131 85 1 15162 200 1 15200 665 1 16095 40 1 16336 299 1 17000 150 1 17197 25 1 17400 118 1 18000 2958 1 18420 0 1 18656 170 2 28905 618 1 19370 1673 1 1

10000 530 1 13140 1 1

10250 35 1 110257 1413 1 110507 141 1 110800 550 1 111989 150 1 113200 421 1 114478 430 1 114500 318 1 115264 416 1 116328 131 1 117610 99 1 118000 1000 1 118141 2307 1 119831 60 1 120000 1370 1 127168 70 1 128000 31000 1 140000 919 1 142000 1900 1 147947 66 1 154969 2234 1 158000 6390 1 1

100000 50000 1 1Totale complessivo 101 12 11 4 128

Conteggio di fistola fistola2ams 1sx ams 5 sx NO A B C Totale complessivo

AMS in I° e V°gg p.o. correlate

1 gg p.o. 5 gg.po pz fistola %ams < 4400 qualsialsi valore 86 2 2,3256ams > 4400 >200 27 27 100ams >4400 < 200 15 0 0

Preliminary Conclusions

• High risk with > than 4000 u/ml in the first p.o. day.

•>200 u/ml in V p.o. day.

1 gg p.o. 5 gg.po pz fistola %ams < 4400 qualsialsi valore 86 2 2,3256ams > 4400 >200 27 27 100ams >4400 < 200 15 0 0

HPB European Chapter, Verona June

2007