Wednesday, 5 June 2019

Diagnosis

Diagnosis



Unfortunately, most patients with PDAC present with non-specific symptoms and are not diagnosed until late in the course of the disease. Common symptoms include pain, particularly epigastric pain that radiates to the back, unexplained weight loss, jaundice, abnormal stools, nausea, and in greater than 10% of the patients, migratory thrombophlebitis. As discussed earlier in the chapter, patients with PDAC sometimes present with new-onset diabetes mellitus or with signs and symptoms of chronic pancreatitis. Of interest, depression is common in patients with PDAC, and in some instances, the diagnosis of depression is established before the patient is found to have cancer.

Challenges in Early Diagnosis and Screening
Screening, early detection, and management of adenomatous polyps, in situ lesions, and other premalignant or potentially malignant entities of the colon, esophagus, cervix, and breast have reduced mortality. PDAC rarely presents early, however, with the increasing use of cross-sectional imaging in recent years, an increasing number of pre-malignant lesions such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are being diagnosed. 

It is also known that the survival of patients with disease detected and resected early is excellent compared to patients with more advanced disease at diagnosis (Wasif et al., 2010). Therefore, pancreatic surgery can be curative for early stage PDAC and the premalignant lesion should be treated if detected. However, the best approach for PDAC screening is yet to be established, as the prevalence of PDAC is relatively low in the general population, and a screening test with reasonable sensitivity, specificity, and high positive and negative predictive values is yet to be identified.

Multi-disciplinary PDAC screening programs such as that of American Cancer of the Pancreas Screening (CAPS) Consortium have screened high-risk individuals with one or more imaging modalities. Family history has been used to enrich for high-risk individuals (Klein et al., 2004). Several CAPS studies have been performed to date with CAPS 4 and 5 still recruiting. In the CAPS 2 study, 10% of the patients (8/78) screened had pancreatic neoplasms detected by EUS, in addition, three patients had five extrapancreatic neoplasms. Of the eight patients, six had benign IPMNs, one had IPMN with invasion and one had pancreatic intraepithelial neoplasia (PanIN) (Canto et al., 2006). The study demonstrated the possibility of diagnosing significant pancreatic and extrapancreatic neoplasms in high-risk individuals. In the CAPS 3 study, the investigators also included MRI and found that CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33% and 43% of high-risk individuals respectively.

The majority (82/85) of the proven or suspected neoplasms identified were IPMNs. The conclusion echoes the CAPS 2 study, that screening is able to detect small pancreatic cysts, including curable, non-invasive high-grade lesions. Authors also concluded that EUS and MRI were better at detecting pancreatic lesions than CT (Canto et al., 2012). CAPS 4 and 5 studies have further expanded the inclusion criteria to include individuals with germline mutations in BRCA1, BRCA2, PALB2, p16/CDKN2A or have hereditary non-polyposis colorectal cancer (HNPCC). CAPS 5 will also evaluate the utility of mutation analysis in pancreatic fluid post secretin stimulation, pancreatic cyst fluid and circulating pancreatic epithelial cells with sporadic disease and normal healthy controls. Despite multi-institutional collaborations with large study population, it will still require extended follow up to demonstrate the impact of screening on PDAC survival (Canto et al., 2013, Ludwig et al., 2011). 

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