1. 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

2. The Anastomotic Leak (alias “spiffero”!) in pancreatic surgery is the underlining phenomena of u Pancreatic fistula u Peripancreatic collections u Peripancreatic abscess u DGE u Bleeding

3. Pancreatic Fistula… DO WE SPEAK THE SAME LENGUAGE?

5. 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.

6. Post-operative Pancreatic Fistula u A Medline search of the last 10 years. u A score was assigned to the reproducible definitions.

7. Post-operative Pancreatic Fistula u The Medline search of the last 10 years identified 26 different definitions. u 14/26 definitions were found suitable for the applied score.

8. Score System ScoreOutput (cc/day)Timing * 1>100>11 2>508-10 3>254-7 4>10>4 * The sum between starting day and P.F.duration

9. 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)

10. Post-operative Pancreatic Fistula u The 4 definitions were applied to 242 pancreatic head resections with P-J carried out from 1997 to 2000 in our Institution. u The Chi-Square test Yates correct test was than applied (p<0.05).

11. 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%)

12. WE NEED A “GENTLEMAN AGREEMENT” AMONG PANCREATIC SURGEONS! upon an objective and internationally accepted definition to allow comparison of different surgical experiences!

13. POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS DEFINITION Members 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).

14. POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS DEFINITION Surgery 2005;138:8 u 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.

15. POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS DEFINITION u Suspicion and diagnosis u 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. u 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. u 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.

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

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

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

19. POST – OPERATIVE PANCREATIC FISTULA: CONSENSUS DEFINITION u Suspicion and diagnosis u 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. u 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. u 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.

20. Pancreatic fistula

22. Role of imaging useful by identifying erosion or migration of the drain

23. POPF GRADING SYSTEM Surgery 2005;138:8 GRADEABC Clincal Conditions WellOften wellIll appearing or bad Specific treatment NoYes/NoYes US/CTNegativeNeg//PosPositive Drain after 3 weeks NoUsually yesYes Reoperatio n No Yes DeathNo Possibly yes Signs of Infections NoYes SepsisNo Yes Readmissio n NoYes/No

24. Grade A Fistulas 10 Criteria are utilized to establish each grade Elevated Drain AmylaseReadmission Persistent DrainageCritical Condition Signs of InfectionRe-operation Diagnostic ImagingSepsis Specific TreatmentsDeath Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8- 13.

25. Grade B Fistulas 10 Criteria are utilized to establish each grade Elevated Drain AmylaseReadmission Persistent DrainageCritical Condition Signs of InfectionRe-operation Diagnostic ImagingSepsis Specific TreatmentsDeath Modified by Pratt et al. fromBassi C et al. Surgery 2005; 138: 8- 13. Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8- 13.

26. Grade C Fistulas 10 Criteria are utilized to establish each grade Elevated Drain AmylaseReadmission Persistent DrainageCritical Condition Signs of InfectionRe-operation Diagnostic ImagingSepsis Specific TreatmentsDeath Modified by Pratt et al. from Bassi C et al. Surgery 2005; 138: 8- 13.

27. International Study Group on Pancreatic Fistula Definition CONSENSUS DEFINITION Conclusion 1 u 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.

28. International Study Group on Pancreatic Fistula Definition CONSENSUS DEFINITION Conclusion 2 u 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.

29. Clinical and Economic Validation of the International Study Group on Pancreatic Fistula Classification Scheme Wande Pratt Shishir K. Maithel Tsafrir Vanounou Zhen Huang Mark P. Callery Charles M. Vollmer, Jr. Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School Doris Duke Charitable Foundation

30. Clinical Validation on 176 Whipple Clinically-Relevant Parameters  Hospital stay (LOS and readmission)  Postoperative complications  Costs

31. Hospital Stay p <.001

32. Complications p =.20 p <.05

33. Total Hospital Costs p <.001

34. 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

35. Still “open” problem … Does the drain fluid amylase contain reflect pancreatic leakege? WE NEED INTERNATIONAL SHARING OF DATA … PRELIMINARY DATA FROM ONE SINGLE CENTRE

36. 137 Evaluated Resections: No POPF VS POPF

37. PD: No POPF VS POPF

38. Left Pancreatctomy: No POPF VS POPF

39. AMS in I° e V°gg p.o. correlate

40. Preliminary Conclusions High risk with > than 4000 u/ml in the first p.o. day. >200 u/ml in V p.o. day.

41. HPB European Chapter, Verona June 2007