**2. Clinico-pathology of pancreato-biliary tumours**

#### **2.1 Pancreatic carcinoma**

In the Western world, pancreatic cancer is the fourth leading cause of cancer related mortality with the approximate incidence of 11 per 100 000, and ranks second after colorectal cancer among all gastrointestinal malignancies (Shaib et al., 2006). Men are more frequently affected than women and over 80% patients are diagnosed at the age older than 60 years. Almost 50% patients have distant metastases at the time of presentation with poor 5-year survival of 5% (Shaib et al., 2006). Recent data suggest that although the mortality rate for males has decreased by 0.4% from 1990 to 2005, the mortality rate for females has increased by 4.4% (Shaib et al., 2006; Jemal et al., 2009). The reason for this gender difference in mortality is unknown. Risk factors for pancreatic cancer include smoking, alcohol, diabetes mellitus, chronic pancreatitis, family history of pancreatic cancer. Patients with hereditary pancreatitis, Puetz-Jeghers syndrome, familial atypical multiple mole melanoma, familial breast and ovarian cancer, Li-Fraumeni syndrome, Fanconi anaemia, ataxiatelangiectasia, familial adenomatous polyposis, cystic fibrosis and possible hereditary nonpolyposis colon cancer syndrome are also at higher risk of having pancreatic cancer (Shaib et al., 2006; Klapman and Malafa, 2008).

Ductal infiltrating adenocarcinoma is the most common type of pancreatic cancer with 78% located in the head, 11% in the body and 11% in the tail (Lillemoe et al., 2000; Ghaneh et al.,

Pancreato-Biliary Cancers – Diagnosis and Management 463

(Katsinelos et al., 2007), and even lesions with intraductal growth (Bohnacker et al., 2005). Given its tumour behaviour, clinical presentation and treatment modality are very different to that of pancreatic cancer and cholangiocarcinoma, ampullary tumours will not be

The imaging modalities involve in the detection, staging and management of pancreatic cancer are computer tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and positron emission tomography (PET) (Clarke et al., 2003; Chang et al., 2009; Peddu et al., 2009). The diagnosis can potentially be made by any, or a combination of the above modalities. The roles and relative importance of these imaging modalities have changed over the last few decades and continue to change with rapid technological advancement in medical imaging. Base on current best available evidence, CT should be used as first line for diagnosis, staging and the assessment of resectability in pancreato-biliary cancer. MRI should be reserved for patients with iodine contrast allergy or who cannot be exposed to radiation or to be used as an adjunct to CT in patients with suspicious liver lesions that need to be to better characterized (Clarke et al., 2003; Peddu et al., 2009). MR cholangio-pancreatography (MRPC) is an essential part of the evaluation for cholangiocarcinoma as it can identify the luminal involvement of the cancer as well as the road map of the biliary tree (Patel, 2006). Such information is not only important in local staging but also critical in determining respectability, type of surgery and/or identifying the dominant obstructive ductal system for biliary drainage. In selected cases, cholangioscopy is helpful by providing direct endoscopic visualization of the intra-ductal lesion that responsible for the biliary stricture (Patel, 2006). The recent development of SpyGlass cholangioscopy system has also allowed

EUS should be used for local staging and assessment of resectability if it remains inconclusive on non-invasive imaging modalities (Chang et al., 2009; Iglesias Garcia et al., 2009). It should also be used in patients with a high clinical suspicion of a lesion that has not been clearly demonstrated using other modalities. EUS-FNA should also be the biopsy route of choice in patients where a tissue diagnosis or tissue from regional lymph nodes may alter the course of treatment, or if neo-adjuvant treatment is contemplated. If there is disagreement between CT and EUS images, then laparotomy and trial of dissection should be considered (Chang et al., 2009). PET/CT should be used selectively such as when metastatic disease is suspected but has not been demonstrated with other imaging modalities (Nguyen and Bartholomeusz, 2011; Serrano et al. 2010). The availability and local expertise of each imaging modality will also influence their use. A suggested management

algorithm for patients with suspected pancreato-biliary cancer is shown in Figure 1.

The role of tumour marker in the diagnosis and management of pancreato-biliary cancers remains controversial (Balzano and Di Carlo, 2008). Carbohydrate antigen 19-9 (CA19-9), which is caused by the up-regulation of glycosyl transferase genes, is the most commonly used marker and can provide useful diagnostic and prognostic information (Duffy et al.

discussed further in this chapter.

tissue sample under direct vision.

**3.1 Tumour markers** 

**3. Investigations of pancreato-biliary cancers** 

2008). Less than 15% of pancreatic cancers are intraductal mucinous papillary neoplasm (IPMN), solid pseudopapillary neoplasm, pancreatoblastoma, mucinous cystadenocarcinoma, adenosquamous carcinoma and acinar cell carcinoma (Ghaneh et al., 2008). Given the preponderance pancreatic head location of the tumours, painless cholestatic symptoms are the most common presentation (Ghaneh et al., 2008). Anorexia, abdominal pain or mass and weight loss often indicate the presence of advanced disease.
