Early detection of pancreatic cancer in patients with intraductal papillary mucinous neoplasms: the pivotal role of endoscopic ultrasound
18 December 2013 (online)
Pancreatic cancer is the fifth leading cause of cancer death in Western countries, and the second highest cause of cancer death among gastrointestinal tumors, with more than 250 000 deaths per year worldwide. With a death rate that nearly equals its incidence, pancreatic cancer is considered to be one of the malignant tumors with the poorest survival  . The only group of patients with pancreatic cancer who have an acceptable prognosis are those with potentially resectable lesions    . In this context, there is significant interest in the screening and early detection of pancreatic cancer.
The knowledge that pancreatic cancer arises from morphologically well-defined, noninvasive precursor lesions, such as intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia  , can be crucial for detection of curable lesions since treating these precursor lesions may prevent the development of pancreatic cancer . Regarding IPMNs, according to the international consensus guidelines of 2012 , surgical resection is indicated for main duct IPMNs. However the management of branch duct IPMNs is still controversial since they are associated with a lower risk of malignancy. Only lesions with high risk stigmata and/or worrisome features are considered to be appropriate for surgery. In this issue of Endoscopy, a study from Kamata et al. provides important information on this subject . The authors followed up patients with branch duct IPMNs without signs of malignancy. During a 5-year follow-up, no mural nodules arose, the lesion increased in size in only 3 % of cases and these were finally diagnosed as IPMN adenomas; thus there were no cases of carcinomas derived from IPMNs in their series. These findings suggest that most branch duct IPMNs can be followed up.
Another important issue is the presence of concomitant pancreatic cancer at the first examination for IPMNs. Kamata et al. identified 11 concomitant pancreatic adenocarcinomas (7 %), which underlines the importance of a careful evaluation of the pancreatic parenchyma at the time of diagnosis of IPMN. But the reported rate for pancreatic cancer found during follow-up of IPMNs, at around 4 % to 7 %, is also important   . Notably, in the study from Kamata et al., the rate for concomitant pancreatic tumors found during follow-up rises to 8.8 %. Given this data, careful evaluation of the pancreatic parenchyma in all of our patients with IPMNs, both at the time of diagnosis and during follow-up, is clearly essential. In this setting, very sensitive imaging techniques should be used to allow detection of these solid tumors within the pancreas at early stages. Kamata et al. provide the first study reporting a long follow-up period (over 5 years) using endoscopic ultrasound (EUS) as the main imaging technique. This approach differs from other studies where computed tomography (CT) scan was the procedure of choice. In fact the authors considered that the use of EUS was crucial with regard to the increased detection rate for pancreatic tumors.
Taking this into account, the imaging technique used for the evaluation of pancreatic diseases appears to be essential in optimizing the detection rate for pancreatic tumors. Up to now, multidetector CT scan, magnetic resonance imaging (MRI), and EUS have been considered to be the main modalities for this purpose, with EUS being the most accurate  . In fact, different studies have shown that the diagnosis of small pancreatic tumors can be missed when CT scan is used. Amongst all those imaging methods, EUS has probably the highest proven sensitivity and specificity among individuals with a clinical suspicion of a pancreatic malignancy  . It has been shown to be the most accurate technique for the identification of small pancreatic tumors; these were often undetected by other imaging techniques       . This turns out to be crucial when evaluating high risk patients, in whom the aim is to detect very small pancreatic lesions ; in a couple of prospective screening studies in familial pancreatic cancer relatives CT scan missed pancreatic neoplasms  . But even more importantly, EUS is also considered to be the best method for ruling out the presence of a pancreatic cancer . This information is highlighted in the study from Kamata et al.: EUS was superior to MRI, CT scan, and abdominal ultrasound, not only for the detection of IPMN-derived pancreatic adenocarcinoma at the first examination, but also for detecting IPMN-concomitant pancreatic adenocarcinoma both at the first examination and throughout the study period.
The role of the different imaging techniques in the evaluation of cystic pancreatic lesions also requires comment. EUS is more sensitive than both CT and MRI for the detection of small, predominantly cystic, pancreatic lesions, with good to excellent concordance between EUS and MRI regarding lesion number, size, and location . A recent expert consensus agreed that initial screening should include EUS and/or MRI . The study from Kamata et al. again confirms these data on the pivotal role of EUS and MRI, but especially EUS, in the study and evaluation of patients with IPMN.
To summarize, for early detection of pancreatic cancer it is essential that patients with IPMN are carefully evaluated, both at the time of diagnosis and during follow-up. EUS can be one of the key tools for this purpose, since it is superior to other imaging techniques in this setting, having the ability to detect small pancreatic adenocarcinomas and excellence in the evaluation of IPMN lesions.
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