Multimodality Treatment in Pancreatic and Periampullary Cancer

Abstract

Pancreatic cancer is the eight most common form of cancer in Europe with 96.000 new cases yearly. This incidence closely matches the mortality rate, thus revealing the aggressive behaviour of this tumour. Five-year survival after diagnosis is only 5% with a median overall survival of 2-8 months. For the patients undergoing surgery, the 5 year survival rate increases to 5% to 25% with a median survival of 12- 15 months. At presentation only 15-20% of the patients have a resectable, and thus possibly curative disease, while the majority of the patients already has locally advanced (i.e. unresectable) or even metastasized pancreatic cancer. The retroperitoneal location of the pancreas plays an important role in the absence of specific complaints. Obstructive jaundice, caused by obstruction of the distal common bile duct by tumours located in the pancreatic head, is a late symptom. This lack of evident clinical manifestations frequently results in a delayed diagnosis and is one of the reasons why pancreatic cancer is usually detected in late stages where curation is no longer an option. In the pancreatic head a variety of tumours can be found, all with its own biological behaviour. Pancreatic ductal adenocarcinoma originating in the pancreatic ducts is the most common and most aggressive tumour resulting in the shortest survival. Periampullary tumours are also often encountered in the pancreatic head. Several definitions of periampullary cancer co-exist.6 Most authors include cancers originating from distal common bile duct, ampulla of Vater or duodenum nearby the ampulla. Some also include cancers located within 2 cm of the ampulla of Vater. This definition may even include “periampullary” cancers of pancreatic ductal origin. Furthermore cystic lesions such as mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN) occur in the pancreas. Even if malignant degeneration is present in these lesions, survival is beneficial compared to ductal adenocarcinomas (5 year survival 24-74%).7 Less frequently pancreatic neuroendocrine tumours (PNETs) or metastasis especially from renal cell carcinomas could be localised in the pancreatic head. In this thesis we have studied several clinical aspects of only patients with pancreatic ductal adenocarcinomas and periampullary tumours and performed experimental in vivo studies using human pancreatic cancer cells.