STAGING OF PANCREATIC CANCER
Andrew L. Warshaw, M.D.
Surgeon-in-Chief and Chairman Department of Surgery Massachusetts General Hospital
W. Gerald Austen Professor of Surgery
Harvard Medical School
The Challenge of Pancreatic Cancer
No screening test Late appearance of symptoms Rapid growth and spread
Pancreatic Cancer
Head 60% Body/Tail 40% 20% resectable <5% resectable 20% 5-yr survival <15% 5-yr survival <3% alive at 5 years
Practical Staging of Cancer
• Resection for potential cure • Confined but locally invasive/unresectable • Metastatic (distant)
Triage decisions
Short-term risk - local experience, age and comorbidity Long-term benefit - possible cure, quality of palliation
Informed preference of patient
Spread of Pancreatic Cancer Local extension/invasion Lymphatics Peri-neural channels Peritoneal cavity Blood
Laparoscopic Staging Results (N=125)
Unsuspected Metastases Gross Metastases Proximal Mass Distal Mass Occult Metastases (Positive cytology only) Sensitivity 39 (31%) 30 (24%) 13/78 (17%) * 17/47 (36%) * 9/94 (9.6%) 30/31 (97%)
*P=0.018
Positive Peritoneal Cytology Predicts Unresectability of Pancreatic Adenocarcinoma
228 patients with radiographically resectable cancers • Positive cytology in 34 (15%) • 26/34 (76%) were Stage IV with metastases • Survival with positive cytology << negative (p<0.0006) • Positive cytology had a positive predictive value of 94%
Merchant (Brennan), J Am Coll Surg, 1999
Staging laparoscopy in periampullary and biliary tumors (all deemed resectable by CT) Site No. Metastases Vascular Idenfified invasion by LUS 22% 21% 17% 55% 9% 0% 17% 12%
Pancreas(head/uncinate) Pancreas(body/tail) Gallbladder Extra-hepatic bile duct
72 12 11 23
Ampulla/duodenum
22
0%
0%
Vollmer (Washington U., St. Louis), Ann Surg, 2002
Laparoscopic ultrasound enhances standard laparoscopy in the staging of pancreatic cancer
Laparoscopic US • Added to accuracy of preop staging by CT • Added 14% to detection of vascular invasion • Increased accuracy of pre-laparotomy staging for resectability to 98%
Minnard (MSKCC), Ann Surg 1998
Laparoscopic ultrasonography for vascular infiltration (50 consecutive patients with pancreatic cancer)
Sensitivity 82% 94% Specificity 53% 80% Accuracy 69% 87%
CT LCU*
Laparoscopy, “because of its unique capabilities to detect even small peritoneal tumor deposits, …is advised in all patients. The additional benefit of (LCU) is not supported by our results …LCU is worth the extra operating time…only in patients with uncertain vascular involvement at CT.”
Pietrabina (U of Pisa), World J Surg 1999 (*Laproscopic contact ultrasonography)
Laparoscopy and laparoscopic ultrasound avoided laparotomy in 20% of upper GI cancers
Site Periampullary Panc.body/tail Esophagus GE junction N 200 15 52 35 Laparotomies avoided 15% 40% 5% 20%
Prox.bile duct
47
40%
Van Dijkum (Amsterdam), JACS 1999
The role of diagnostic laparoscopy in pancreatic and periampullary malignancies
“Perioperative computed tomography is a reliable technique to detect tumor metastasis…unlike other investigators, we found that only…14% of patients with pancreatic cancer might profit from laparoscopy.”
Friess (U. of Bern) JACS 1998
Diagnostic laparoscopy for periampullary and pancreatic cancer: What is the true benefit?
• “after patients undergoing operative palliation were eliminated, a nontherapeutic laparotomy would have been precluded by the use of diagnostic laparoscopy in only 2.3% of patients with periampullary cancers (4 of 171 patients).”
Barriero (Johns Hopkins), J Gastrointest Surg 2002
The Palliative Whipple Resection
Intended Debulking or Intra-operative Escape
(bad news in the pathology report)
• Survival Benefit? • Dissemination? • Quality of Life?
Median Survival following R1 or R2 Pancreaticoduodenectomy
Reference Year # of R1 or R2 resections 1976 17 1990 1993 1995 1995 54 37 28 58 64 Positive margin R1/R2 R1/R2 R1/R2 R2 R1/R2 R1/R2 Median survival (months) 8 10 11 9 10 12
Tepper et al Trede et al Willett et al Nitecki et al Yeo et al
Lillemoe et al 1996
Pisters, Brit J Surg, 2001
Pancreatic Cancer: Unresectable Disease
• Palliate with biliary tract decompression (surgical bypass or stent placement) and pain management • Palliate with bypass for duodenal/gastric outlet obstruction • Chemoradiation +/- IORT for pain
Pancreatic cancer patients with circulating cancer cells in blood.
• Patients with peritoneal metastases – AE1/AE3 - positive cells 67%* (10/15)
• Patients without peritoneal metastases – AE1/AE3 - positive cells 14%* (2/14)
* p + 0.008 two-tailed Fisher exact test
Selective Use of Laparoscopy in Potentially Resectable Pancreatic Cancer
• Pancreatic adenocarcinoma, not ampullary, duodenal, NE, cystic • High-quality CT to detect mets, vascular involvement • Larger primary tumors (Size?) • Location in neck, body, tail • Equivocal CT, marked weight loss, very high CA19-9, pain