Updates on surgery for pancreatic cancer

1. Updates on surgery for pancreatic cancer Paul B. S. Lai Division of Hepato-biliary and Pancreatic Surgery Department of Surgery Chinese University of Hong Kong

2. Prognosis of pancreatic cancer • Typically present late in the course of disease and they are usually inoperable • locally advance • presence of metastasis • For those patients with resection done • high operative mortality • high recurrence rate • Pancreatic cancer = Death sentence?

3. Resection rates for pancreatic cancer

4. Assessment of resectability • CT scan • Remain the gold standard with 80 to 90% accuracy in predicting resectability • Can be further improved with the use of multi-slice scanners with arterial and portal venous phases of contrast enhancement • ERCP • Can only detect cancers when they impinge on pancreatic duct • Small early cancers and small uncinate tumours may be missed • EUS • Highly sensitive in picking up small lesions and invasion to major vascular structures

5. Laparoscopy and laparoscopic USG • Can detect occult metastatic lesions in the liver and peritoneal cavity in 10-35% of cases not identified by other imaging modalities • True value remains controversial

6. IVC invasion not detected on CT scan duodenum IVC Head

7. Surgical resection -What to do and what not to do?

8. Patients with obstructive jaundice Should we drain the biliary system before further intervention?

9. Pre-operative biliary drainage • No clear benefits or harms in terms of surgical outcome • Memorial Sloan-Kettering reported an increased overall morbidity and mortality after pre-operative drainage • Others found slight increase in wound infection • Clearly, a lot of units would be forced to stent their patients pre-operative for logistic reasons • Trials are still underway

10. Pre-operative management • Imaging • CT scan mostly • MRCP (not a routine) • Cholangiogram (from ERCP or PTBD) • Drainage of biliary tree pre-op • Usually drained due to waiting list consideration • Prophylactic octreotide • Optional • Bowel preparation • Not a routine • Informed consent • Quoting 5% mortality

11. Union International Contre la Cancer staging of pancreatic cancer (2002) N0, no regional lymph node metastasis; N1, regional lymph node metastasis; M0, no distant metastasis; M1, distant metastasis.

12. Operative procedures • Routine laparoscopy • For detection of small peritoneal metastases • Routine laparoscopic USG assessment • To assess for small liver lesions and the status of the SMV and PV • Incision • Roof-top • Determination of operability • Mobilization of pancreatic head and duodenum • Exploration of the lesser sac • Cholecystectomy and transection of CHD

14. Increasing use of TA 90 to transect uncinate flush to SMA by palpation

15. Assess the root of transverse mesocolon for tumour involvement

16. Kocher’s manoeuvre

17. Full Kocherization

18. Transection of CHD above cystic duct insertion to expose the PV better Tunneling of the anterior surface of PV

19. To transect antrum or D1

20. Annals of Surgery 2004 Standard Whipple versus PPPD • 3 prospective randomized trials • Taiwan (Lin et al 1999; BJS) – 31 patients only • Bern (Seiler et al 2004; BJS) – 66 vs. 64 • Netherlands (Tran et al 2004; Ann Surg) – 83 vs. 87 • Very similar outcomes • No significant difference in long-term survival

21. How to reconstruct pancreatic-enteric anastomosis ? • End-to-side duct-to-mucosa technique with or without stent • Verona study showed no difference between duct-to-mucosa and end-to-side technique Bassi C. et al., Surgery 2003; 134:766-771

22. Prospective series of 123 patients • Cut surface of pancreas evaluated for blood supply • Those deemed inadequate would have the pancreas cut back • to improve the blood supply • Leakage rate = 1.6% (2 in 123 patient) Strasberg et al., J Am Coll Surg 2002;194:746-760.

24. Anatomy of the pancreatic neck and uncinate process

25. Pancreatico-jejunostomy – duct-to-mucosa & end-to-side

26. Pancreatico-jejunostomy – duct-to-mucosa & end-to-side

28. How to reconstruct pancreatic-enteric anastomosis ? • Pancreatojejunostomy (PJ) vs. Pancreatogastrostomy (PG) • Johns Hopkins prospective randomized study showed similar leakage rate (11% vs. 12%) with no peri-operative mortality • Another retrospective study of 441 patients from Germany showed less leakage and lower mortality associated with leakage in the PG group Yeo CJ et al., Ann Surg 1995; 222:580-588. Schlitt HJ et al., BJS 2002; 89:1245-1251.

29. Radical enough?

30. Post-operative management • ICU not routine • A short course of antibiotics • Cefuroxime, metronidazole • Octreotide SC • Not a routine, sometimes used for insecure PJ • Drains removed after confirming low amylase content • NG removed after output less than ~200ml a day

31. Management of complications • PJ leak • Drainage + TPN • Relaparotomy in selected cases • Intraabdominal collections • Percutaneous drainage usually adequate • Wound infection • Rather common • ? Would protection • ? Delayed primary closure • Delay gastric emptying • Functional versus technical • Usually settles with conservative treatment • Bile leak • Quite rare, drainage should be adequate • Post-operative bleeding • Rare, but need re-laparotomy if it does occur • Association with PJ leakage?

32. Post-op adjuvant therapy – in PWH • Not a routine • No standard protocol • RT alone, chemotherapy alone, chemo-RT combined • Overall survival of patients with pancreatic head cancer after PPPD or Whipple procedure • Still very poor due to recurrent diseases • Awaiting more research in this area of management

33. Role of extended lymphadenectomy ? • Original hypothesis • radical pancreatic resection as a means of increasing resectability rates and improving the outcome for patients • Rationale • Largely found on the patterns of failure after Whipple resection as a result of local intra-abdominal recurrence • removing all peri-pancreatic tissues and LNs that carry tumour cells should translate into better survival

34. Dr. Joseph Fortner’s 1973 illustration – total pancreaticoduodenectomy and subtotal gastrectomy, with arterial and venous resection (from Surgery 73:307-320; 1973)

35. Johns Hopkins prospective randomized study April 1996 to June 2001

36. Johns Hopkins prospective randomized study April 1996 to June 2001 • 30-40% distal gastrectomy • including LN stations 5 & 6 and some stations 3 & 4 • Including portions of greater omentum and lesser omentum along the course of right gastroepiploic artery and right gastric artery • retroperitoneal dissection • extended from right renal hilum to left lateral border of the aorta in the horizontal axis • from portal vein to below the third part of duodenum in the vertical axis • (LN station 16a2 and 16b1 + sampling of celiac LN [station 9]

37. Johns Hopkins prospective randomized study April 1996 to June 2001 • Actuarial survival curves for all patients (n=285; P=0.79) • 1-, 3-, and 5-year survival rates are 80%, 44% and 23% for the standard group • 1-, 3-, and 5-year survival rates are 77%, 44% and 29% for the radical group

38. Role of extended lymphadenectomy ? • 2 randomized trials • European lymphadenectomy study group (40 vs. 41 patients) • Johns Hopkins group (146 vs. 148 patients) • No survival benefit with extended lymphadenectomy • No substantial evidence for routine use of extended lymphadenectomy for pancreatic cancer Pedrazzoli P et al., Ann Surg 1998;228:508-517. Yeo CJ et al., Ann Surg 2002; 236:355-368.

39. Other interventions that may affect surgical outcomes • Total parental nutrition • Does more harm than good • Continuous or cyclic enteral nutrition • Cyclic enteral feeding ass. earlier oral feeding • Somatostatin and its analogues • Highly controversial • Results were very different between European and US studies • Differences in study design may account for the different outcomes

40. Adjuvant therapy after PD • Non-randomized studies in the 80s suggested some improvement in survival with adjuvant therapy • European study group for pancreatic cancer (ESPAC-1 trial) • rather complicated 2 x 2 factorial randomization • Observation vs. chemoradiation alone vs. chemotherapy alone vs. combination of the two • Overwhelming advantage for chemotherapy (5-year actuarial survival of 29.0%) Neoptolemos JP et al., NEJM 2004; 350:1200-1210.

42. Kaplan-Meier estimates of survival according to whether or not patients received systemic chemotherapy

43. Does volume counts?

44. Volume does count for resection of pancreatic cancer

45. Figure 15: The unadjusted 30-day mortality and hospital mortality rates after PD among the 13 HA hospitals. *Indicates statistical significance

46. Any novel therapy?

47. Molecular and genetic studies of pancreatic cancer

48. Summary • The resection rate of pancreatic cancer is increasing with better imaging modalities • Pre-operative drainage has been showed to have no added advantage but many are still practicing it due to logistic reasons • PPPD has the same oncological clearance as standard Whipple • Improved techniques in fashioning of PJ have lead to a reduction in leakage and mortality • The expected survival benefit of extended lymphadenectomy has not been demonstrated • Systemic chemotherapy improves survival after PD • Overall prognosis is still bad • More basic researches may help to improve the treatment results

49. 革命尚未成功 同志仍需努力