pancreatic cancer - isc - web version

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					    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
      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?
  Resection rates for pancreatic cancer
                            Study            No. of                            Resection rate
Reference         Year      Period          patients                Region          (%)

Bramhall et al.   1995    1977-1987             5672       West Midlands, UK        2·6

NYCRIS            2000    1986-1994             3278       Northern and             4·0
                                                           Yorkshire, UK
Hedberg et al.    1998    1977-1991              575       Mälmo, Sweden            4·2

Sener et al.      1999    1985-1995          100 313       USA                      9·0

   NYCRIS, Northern and Yorkshire Cancer Registry and Information Service.
            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
  – Can only detect cancers when they impinge on
    pancreatic duct
  – Small early cancers and small uncinate tumours may be
  – Highly sensitive in picking up small lesions and invasion
    to major vascular structures
Laparoscopy and laparoscopic USG
  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
 True value remains controversial
IVC invasion not detected on CT scan


     Surgical resection -
What to do and what not to do?
 Patients with obstructive jaundice

Should we drain the biliary system
   before further intervention?
       Pre-operative biliary drainage

 No clear benefits or harms in terms of surgical
 Memorial Sloan-Kettering reported an increased
  overall morbidity and mortality after pre-operative
 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
      Standard Whipple versus PPPD

 3 prospective randomized trials of Surgery 2004
   – 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
  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
• 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.
  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
   – 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.
Radical enough?
 Role of extended lymphadenectomy ?

 Original hypothesis
   – radical pancreatic resection as a means of increasing
     resectability rates and improving the outcome for

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

 2 randomized trials
   – European lymphadenectomy study group (40 vs. 41
   – Johns Hopkins group (146 vs. 148 patients)
   – No survival benefit with extended lymphadenectomy

                 Pedrazzoli P et al., Ann Surg 1998;228:508-517.
                 Yeo CJ et al., Ann Surg 2002; 236:355-368.
Johns Hopkins prospective randomized
    study April 1996 to June 2001
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
 Role of extended lymphadenectomy ?

 2 randomized trials
   – European lymphadenectomy study group (40 vs. 41
   – Johns Hopkins group (146 vs. 148 patients)
   – No survival benefit with extended lymphadenectomy
 No substantial evidence for routine use of
  extended lymphadenectomy for pancreatic

                Pedrazzoli P et al., Ann Surg 1998;228:508-517.
                Yeo CJ et al., Ann Surg 2002; 236:355-368.
    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
   – Differences in study design may account for the
     different outcomes
           Adjuvant therapy after PD

 Non-randomized studies in the 80s suggested
  some improvement in survival with adjuvant
 European study group for pancreatic cancer
  (ESPAC-1 trial)
   – rather complicated 2 x 2 factorial randomization
   – Observation vs. chemoirradiation 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.
Kaplan-Meier estimates of survival according to whether
or not patients received systemic chemotherapy
Does volume counts?
          Volume does count for resection of pancreatic cancer
                                                                                 Mortality rate (%)
Reference (Year)            Region        Study        No. of        No. of       High-       Low-
                                          period    Institutions   resections    volume      volume
                                                                                hospitals   hospitals
Studies from the USA
Lieberman et al. (1995)   New York      1984-1991       184          1972          5.5      11.8-18.9
Janes et al. (1996)       USA           1983-1990       978          2263          4.2         7.7
Gordon et al. (1995)      Maryland      1988-1993       39            501          2.2       13-19.1
Glasgow et al. (1996)     California    1990-1994       298          1705          3.5      6.9-14.1
Gordon et al. (1998)      Maryland      1984-1995       43           1093          1.8        14.2
Begg et al. (1998)        USA           1984-1993                     742          5.8        12.9
Birkmeyer et al. (1999)   USA           1992-1995      1246          7229          4.1      12.7-16.1

Studies from Europe
Neoptolemos et al.        UK            1976-1996       21           1026          5.9      8.3-27.6
Gouma et al. (2000)       Netherlands   1994-1998                    1126          0.9        16.0
NYCRIS[9] (2000)          Yorkshire,    1986-1994       17            130          7.8        28.6
Nordback et al. (2002)    Finland       1990-1994       33            374          3.6        12.9
Any novel therapy?
Molecular and genetic studies of
      pancreatic cancer
 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
 PPPD has the same oncological clearance as standard
 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

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