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Evidence-based diagnosis and staging of pancreatic cancer

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Only 20% of patients who present with pancreatic cancer will be amenable to potentially curative resection. Therefore, it is necessary to reliably identify patients who might benefit from major surgical intervention by employing the appropriate staging methods. In this review, the pros and cons of each imaging technique are discussed and an algorithm for single and combined use of the different imaging modalities is proposed. To date, contrast-enhanced multi-detector row helical CT (MDR-CT) together with endoscopic ultrasound (EUS) remain the first staging methods of choice. MDR-CT has a high sensitivity for identifying vascular invasion and EUS is able to detect lesions as small as 2–3 mm. ERCP is performed mainly in patients with biliary obstruction with the option for therapeutic intervention during the same session. MRI with MR-angiography, MRCP, PET/CT and staging laparoscopy are additional modalities which might give further information in cases of equivocal findings by MDR-CT and EUS. The role of tumour markers such as CA 19-9 and CEA is reserved for monitoring and diagnosing post-surgery recurrence. Cytological or histological confirmation should usually be performed in patients that are not eligible for surgery prior to the commencement of palliative radio- or chemotherapy. In the routine clinical setting, MDR-CT and EUS play the predominant roles by providing the most cost-effective and accurate means for diagnosing and staging most cases of pancreatic cancer.

Section snippets

Ultrasonography

Ultrasonography is frequently the first imaging modality employed in patients presenting with symptoms suspicious for a pancreatic malignancy. It is readily available, safe, and provides rapid assessment of the pancreas in most patients. It has a high sensitivity for detecting biliary tract dilatation and establishing the level of obstruction. Visualisation of the pancreatic parenchyma and duct is less reliable due to body habitus and overlying bowel gas. The sensitivity of US in the detection

Endoscopic ultrasonography (EUS)

Endoscopic ultrasonography (EUS) was developed in the early 80's to improve the unsatisfactory diagnostic approaches available for pancreatic diseases in those days.13 Since, then a dramatic technological progress has taken place and has in particular revolutionised imaging of the pancreas. Due to this development and the additional possibility of taking biopsies using real-time sonographic guidance, EUS has become an indispensable and valuable standard imaging modality for the diagnosis of

Intraductal ultrasonography

Standard echoendoscopes are limited by their large diameter and resultant inability to gain access to ductal systems or poststenotic intraluminal spaces. They are also limited by their relatively low scanning frequencies (7.5/12 MHz), leading to reduced image resolution. Ultrasound miniprobes therefore were developed to offer access to narrow intraluminal spaces including the pancreaticobiliary system. Intraductal ultrasonography (IDUS) using small-caliber, high-frequency catheters (5–10 F, 12–30 

Computed tomography (MDR-CT)

MDR-CT is the most widely available and best validated tool for pancreatic imaging.33 Estimates of the specificity for assessing unresectability using CT vary in older studies from 100% to less than 50%.34, 35 However, most of these previous studies used older generation CT scanners significantly different to modern multi-detector 16- or 40-row detector CT scanners.

With the advent of MDR-CT, imaging of the pancreas has entered a new era. The introduction of multiple rows of detectors and

Endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) has a played an important role in the diagnosis of pancreatic diseases since it was introduced in the 1960s. It is a highly sensitive tool to visualise the anatomy of the hepato-biliary tree. Furthermore, it provides the opportunity to collect pancreatic juice for brush cytology, biopsy and genetic analyses. An early meta-analysis evaluated data from almost twenty studies and found a sensitivity of 92% and specificity of 96% for diagnosing

Magnetic resonance imaging (MRI)

Magnetic resonance imaging offers excellent soft tissue contrast, potentially providing the best mode of imaging for soft tissue lesions. However, the signal-to-noise ratio and relatively slow speed of image acquisition mean that spatial resolution has been worse than multidetector spiral CT, and a large number of artefacts have been produced with bowel movement. Therefore, up to very recently, MRI has not been as valuable a tool as MDR-CT in the diagnosis of pancreatic cancer.54 Both

Magnetic resonance cholangiopancreatography

Magnetic resonance cholangiopancreatography (MRCP, in RARE and HASTE technique) was developed in the early 90's providing a highly sensitive tool for non-invasive imaging of the pancreato-biliary tree. MRCP is safe, relatively fast, and allows visualisation of obstructed ducts, even when they are inaccessible to ERCP or PTC.

In a recent meta-analysis, MRCP was found to be highly sensitive for detecting and localising pancreato-biliary obstructions, but less so for diagnosing malignant conditions.

Positron emission tomography and integrated PET/CT

Positron-emission-tomography (PET) is a non-invasive diagnostic modality with a high sensitivity for distant metastases in several tumor entities. A positron-emitting compound is injected intravenously, and its accumulation is displayed by the PET scanner. The most frequently used compound for tumor staging is 18-fluoro-deoxy-glucose (18-FDG) 66 making use of the high glucose uptake in proliferating tumors.

The sensitivity of PET for detecting pancreatic cancers ranges from 71 to 92% with

Laparoscopy

Laparoscopy has been a controversial component of the complex staging algorithms for patients with suspected pancreatic cancer. Its main role is to detect occult intra-abdominal metastatic disease. During the procedure, which is associated with minimal morbidity, any suspicious lesion can be biopsied and peritoneal cytology can also be obtained by instilling normal saline into the peritoneum.74, 75

The yield from laparoscopy in detecting metastatic disease, especially of small volume peritoneal

Tumour markers

In addition to imaging modalities, various laboratory tests are frequently being used for the diagnosis of pancreatic cancer as an adjunct to imaging techniques. A number of secreted proteins have been identified with increased serum levels in patients with pancreatic cancer. Apart from helping to diagnose the tumour, these tumour markers are thought to be useful for (i) indication of prognosis, (ii) assessment of therapeutic efficacy, and (iii) detection of residual or recurrent cancer.87

Cytological or histological confirmation

Due to the significant number of non-diagnostic sampling and the theoretical possibility of tumour seeding, histological or cytopathological assessment is generally not recommended for patients that are eligible for curative resection of the tumour. The patient will generally go straight to theatre if the tumour is resectable on radiological criteria. However, since various histological types of tumours with varying prognostic outcomes and therapeutic options such as neuroendocrine tumours,

Diagnostic algorithm for staging of pancreatic cancer

Pancreatic cancer is staged using the TNM-(Table 2) and the AJCC-(American Joint Committee on Cancer) classification (Table 3). Clearly the main role of staging pancreatic adenocarcinoma is to ensure that the patient receives the most appropriate treatment. Imaging features that are consistent with unresectability include local invasion of surrounding structures or metastatic spread. To date, the predominant imaging modalities for staging of pancreatic cancer are contrast-enhanced spiral CT and

Summary

In the routine clinical setting, multi-detector helical CT and EUS play the predominant roles by providing the most cost-effective and accurate means for diagnosing and staging most cases of pancreatic cancer. Clearly, the choice of staging modalities varies among different centres depending on the availability of the high-end imaging modalities and the expertise of the operators, e.g. in performing EUS. Additional techniques such as MRI, MRCP, PET/CT of laparoscopy in staging pancreatic cancer

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