Multidetector computer tomography in the pancreatic adenocarcinoma assessment: an update
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Ductal adenocarcinoma of the pancreas is one of the most aggressive forms of cancer, with only a minority of cases being resectable at the moment of their diagnosis. The accurate detection and characterization of pancreatic carcinoma is very important for patient management. Multidetector-row computed tomography (MDCT) has become the cross-sectional modality of choice in the diagnosis, staging, treatment planning, and follow-up of patients with pancreatic tumors. However, approximately 11% of ductal adenocarcinomas still remain undetected at MDCT because of the lack of attenuation gradient between the lesion and the adjacent pancreatic parenchyma. In this systematic literature review we investigate the current evolution of the CT technique, limitations, and perspectives in the evaluation of pancreatic carcinoma.
KeywordsPancreatic adenocarcinoma Multidetector computer tomography Perfusion CT Dual-source CT
Area under the curve of peritumoral Tissue
Blood flow of peritumoral tissue
Locally-advanced pancreatic cancer
Multidetector-row computed tomography
Magnetic resonance imaging
Pancreatic adenocarcinoma is one of the most aggressive forms of cancer. It is the fourth most common cause of cancer-related mortality worldwide. The prognosis of pancreatic cancer is still bleak, as the 5-year survival rate is less than 5% and the mortality rate has not declined over the last few decades, with an increasing global incidence of nearly 340,000 in 2012. The incidence rate near equaling that of its mortality rate . At presentation, about 40% of patients with pancreatic cancer are diagnosed with metastatic disease (stage IV) and 40% are diagnosed with locally-advanced pancreatic cancer (LAPC) [1, 2].
The accurate characterization of pancreatic adenocarcinoma is very important for patient management. Computer tomography (CT) and magnetic resonance imaging (MRI) are the most important modalities for evaluating pancreatic lesions. A precise diagnosis of pancreatic tumor is not always simple because the tumor can have atypical imaging features and many other disorders may mimic pancreatic adenocarcinoma [3, 4]. Multidetector row (MD) CT has become the modality of choice in the preoperative diagnosis and staging of the disease and in treatment planning and follow-up in patients with pancreatic tumors . Although many studies have investigated the effect of different techniques of contrast medium injection for improving the enhancement of the pancreas and peripancreatic vasculature during the pancreatic parenchymal phase [6, 7, 8, 9, 10], approximately 11% of ductal adenocarcinomas remain undetected at MDCT. This is because of the lack of a visible attenuation difference between the tumor and the adjacent pancreatic parenchyma. In these cases, recognition secondary signs (e.g. main pancreatic duct dilatation or the interrupted duct sign) becomes mandatory to detect the lesion . In this review we investigate the evolution of the MDCT technique, limitations, and future prospects in the evaluation of pancreatic adenocarcinoma.
Materials and Methods
Data for this review were identified by searches of the PubMed database using a multimodal strategy. The following search terms were employed: CT in pancreatic cancer, functional CT in pancreatic cancer, CT in advanced pancreatic cancer, CT in advanced pancreatic adenocarcinoma after chemotherapy. The inclusion criteria were: clinical study evaluating pancreatic adenocarcinoma, clinical study evaluating new functional imaging criteria in the CT study of patients with pancreatic adenocarcinoma, and clinical study evaluating follow-up after chemotherapy of patients with advanced pancreatic adenocarcinoma. Articles published in the English language from January 2003 to June 2016 were included. The references of these articles were also analyzed to identify original studies that were not identified by the search of the data. Exclusion criteria unavailability of full text and absence of original research data (reviews, editorials, case reports, etc.).
The enhancement kinetics of the normal pancreas follows arterial dynamics. There is a longer delay necessary to increase the enhancement of the interstitial spaces of the organ of interest, and hence to increase the contrast to the ductal system and the lesion-to-background contrast for hypovascular pancreatic adenocarcinomas. Pancreatic imaging thus also benefits from high iodine flux and accurate scan timing relative to the arrival of contrast media in the abdominal aorta but also improves with larger contrast medium volumes. Scan timing is critical, and best lesion-to-background contrast is achieved approximately 20 to 25 s after contrast medium arrival in the aorta (for injection durations of 30 s, and scan times of approximately 5 s) .
To reduce radiation dose and increase conspicuity of tumor Brook et al.  evaluated the Split-bolus technique during the study of the pancreas. Split-bolus contrast material administration is based on injection of various amounts of contrast material in two or three parts with a variable pause while scanning is performed only once, so to obtain a combined-phase images in a single scan. In this study has been demonstrated that with a single combined phase, split-bolus spectral CT examination resulted in vascular, liver, and pancreatic attenuation and pancreatic tumor conspicuity equal to or higher than those obtained with a standard combination of two-phase pancreatic CT, with a 43% reduction in the radiation dose .
To identify and characterize a pancreatic lesion is essential not only the phase of study but also the concentration, the injection flow rates and volumes. Yanaga et al.  evaluated a protocol with a fixed contrast material injection dose and one with a dose tailored to patient body weight and has been demonstrated that with the fixed contrast material dose protocol, pancreatic enhancement during the pancreatic parenchymal phase was significantly worse in the heavier patients (body weight of 60 kg or greater) than in the lighter patients (body weight of less than 60 kg). On the other hand, there was no significant difference between the two weight groups with the protocol in which contrast material dose was tailored to patient weight. So CT protocols that deliver a contrast material dose tailored to patient weight at a fixed injection duration yield satisfactory pancreatic enhancement in patients of different body weights  and that increases the tumor detection. Liu et al.  demonstrated that although the pancreas, pancreatic malignancies and other abdominal organs are more enhanced in higher iodine concentration group in arterial and/or portal venous phase, the detection and demarcation of pancreatic adenocarcinomas was not found to improve with the higher iodine concentration so as demonstrated also by Fenchel et al. . These results demonstrate that where it has to use contrast agents at low dose, as in patients with renal impairment, there is not the risk of identifying a pancreatic tumor [37, 38]. Then for an accurate study of the pancreatic parenchyma it is more important than a correct dose of contrast, considering the patient’s body weight, which is not the concentration of the contrast [36, 37, 38].
Although radical resection is still the only curative treatment for pancreatic cancer, it is generally accepted that a multimodality strategy is necessary for its management, because at the time of diagnosis about 40% of patients with pancreatic cancer are diagnosed with metastatic disease (stage IV) and the remaining 40% are diagnosed with LAPC [1, 2, 39]. After neoadjuvant chemo-radiotherapy (CRT) or ablation therapy, CT is usually used to evaluate treatment response and to restage tumors. CRT, especially radiation therapy, may induce fibrosis, which confounds viable tumor analysis at CT reducing preoperative staging accuracy . Also the study of Cassinotto et al.  confirmed the decrease in the diagnostic performance of the CT to reevaluate resectability after neoadjuvant therapy of pancreatic tumor. Morgan  demonstrated that the CT sensitivity for prediction of resectability tends to be lower for patients with locally advanced pancreatic cancer that has been downstaged by neoadjuvant therapy than for controls who did not receive preoperative therapy. In patients undergoing chemo radiotherapy the most limits of CT is differentiating a residual tumor from the fibro-inflammatory tissue, so other techniques are needed to optimally evaluate the tumor response. MRI with diffusion sequencing and dynamic analysis would enable to differentiate between tumor tissue and edematous fibrosis [2, 4, 39]. Similarly, CTp could help provide functional information and aid in the characterization of residual tissue .
Although MDCT is the modality of choice in the preoperative diagnosis and staging and in treatment planning and follow-up of patients with pancreatic cancer, there is an 11% of pancreatic adenocarcinoma is being unrecognized. Therefore it is necessary to optimize the technique, with a dose of the contrast medium adequate to the weight of the patient, with a proper delay after administration of the contrast medium. Parenchymal pancreatic phase is better than arterial phase. Dual-source, dual-energy MDCT and CTp improve the detection of pancreatic adenocarcinoma, increasing the conspicuity of nearly isoattenuating, small lesions. CTp, additionally, provides functional information and can aid in the assessment of residual viable tumor tissue after CRT.
We are grateful to Dr. Alessandra Trocino from the National Cancer Institute of Naples for providing excellent bibliographic service and assistance.
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Each author have participated sufficiently in any manuscript editing, revision and submission to take public responsibility for its content. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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