Diagnostic accuracy of different scans following a CT scan for assessing whether pancreatic and periampullary cancer is resectable

Review question

How well do different scans identify whether pancreatic and periampullary cancer is resectable (can be surgically removed) in patients with pancreatic cancer in whom computed tomography (CT) scan suggests that the cancer can be removed?

CT scan involves a series of X-rays which are combined by a computer to provide detailed images of the area of the body X-rayed.

Background

The pancreas is an organ situated in the abdomen close to the junction of the stomach and small bowel. It secretes digestive juices that are necessary for the digestion of all food materials. The digestive juices secreted in the pancreas drain into the upper part of the small bowel via the pancreatic duct. The bile duct is a tube which drains bile from the liver and gallbladder. The pancreatic and bile ducts share a common path just before they drain into the small bowel. This area is called the periampullary region. Surgical removal is the only potentially curative treatment for cancers arising from the pancreatic and periampullary regions. A considerable proportion of patients undergo unnecessary major open abdominal exploratory operation (laparotomy) because their CT scan has underestimated the spread of cancer. If the cancer is spread within the abdomen as identified during the major open operation, the main treatment is chemotherapy which does not cure the cancer but may improve survival. Thus the major open abdominal operation with its associated risks can be avoided if the spread of cancer within the abdomen is known before the major operation. Determining the extent of cancer is called "staging" the cancer. Usually the minimum test used for staging is the CT scan. However, CT scan can understage the cancer, i.e. it can underestimate the spread of cancer. Various other scans can be used in addition to CT scan in order to find out if pancreatic cancer is resectable (able to be surgically removed). These include the following tests.

1. Magnetic resonance imaging (MRI): use of a powerful magnet to produce images of different tissues of the body.

2. Positron emission tomography (PET scan): small amount of radioactive glucose (sugar) is used to differentiate between different tissues. It utilises the property that cancer cells often use more glucose than normal cells).

3. Endoscopic ultrasound (EUS); the use of an endoscope, a camera introduced into the body cavities to view the inside of the body. An ultrasound (high-energy sound waves) probe at the end of the endoscope is used to differentiate different tissues.

In addition, a combination of PET-CT may be performed instead of CT.

Different studies report different accuracy of these tests in assessing whether the cancer can be removed. In this review, we identified all such studies and used appropriate mathematical methods to identify the average diagnostic accuracy of these tests for staging pancreatic and periampullary cancers considered to be removable after a CT scan.

Study characteristics

We included two studies with a total of 34 patients in this review. Both studies evaluated the diagnostic performance of EUS. This evidence is current to 5 November 2015.

Quality of the evidence

Of the two studies, one study was conducted as well as such a study could be conducted. The methodological quality of the other study was poor.

Key results

The two included studies showed that in those people with pancreatic cancer in whom CT alone showed their cancer was capable of being fully surgically removed, 61% (61 out of 100) would prove to have cancer that was too fully spread to make this possible when a laparotomy was attempted. Due to the small sample size, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer found to have resectable disease on CT scan.

Authors' conclusions: 

Based on two small studies, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. No studies have assessed the utility of EUS in people with periampullary cancer.

There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer or periampullary cancer found to have resectable disease on CT scan.

Read the full abstract...
Background: 

Periampullary cancer includes cancer of the head and neck of the pancreas, cancer of the distal end of the bile duct, cancer of the ampulla of Vater, and cancer of the second part of the duodenum. Surgical resection is the only established potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Other imaging methods such as magnetic resonance imaging (MRI), positron emission tomography (PET), PET-CT, and endoscopic ultrasound (EUS) have been used to detect local invasion or distant metastases not visualised on CT scanning which could prevent unnecessary laparotomy. No systematic review or meta-analysis has examined the role of different imaging modalities in assessing the resectability with curative intent in patients with pancreatic and periampullary cancer.

Objectives: 

To determine the diagnostic accuracy of MRI, PET scan, and EUS performed as an add-on test or PET-CT as a replacement test to CT scanning in detecting curative resectability in pancreatic and periampullary cancer.

Search strategy: 

We searched MEDLINE, Embase, Science Citation Index Expanded, and Health Technology Assessment (HTA) databases up to 5 November 2015. Two review authors independently screened the references and selected the studies for inclusion. We also searched for articles related to the included studies by performing the "related search" function in MEDLINE (OvidSP) and Embase (OvidSP) and a "citing reference" search (by searching the articles that cite the included articles).

Selection criteria: 

We included diagnostic accuracy studies of MRI, PET scan, PET-CT, and EUS in patients with potentially resectable pancreatic and periampullary cancer on CT scan. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies.

Data collection and analysis: 

Two review authors independently performed data extraction and quality assessment using the QUADAS-2 (quality assessment of diagnostic accuracy studies - 2) tool. Although we planned to use bivariate methods for analysis of sensitivities and specificities, we were able to fit only the univariate fixed-effect models for both sensitivity and specificity because of the paucity of data. We calculated the probability of unresectability in patients who had a positive index test (post-test probability of unresectability in people with a positive test result) and in those with negative index test (post-test probability of unresectability in people with a positive test result) using the mean probability of unresectability (pre-test probability) from the included studies and the positive and negative likelihood ratios derived from the model. The difference between the pre-test and post-test probabilities gave the overall added value of the index test compared to the standard practice of CT scan staging alone.

Main results: 

Only two studies (34 participants) met the inclusion criteria of this systematic review. Both studies evaluated the diagnostic test accuracy of EUS in assessing the resectability with curative intent in pancreatic cancers. There was low concerns about applicability for most domains in both studies. The overall risk of bias was low in one study and unclear or high in the second study. The mean probability of unresectable disease after CT scan across studies was 60.5% (that is 61 out of 100 patients who had resectable cancer after CT scan had unresectable disease on laparotomy). The summary estimate of sensitivity of EUS for unresectability was 0.87 (95% confidence interval (CI) 0.54 to 0.97) and the summary estimate of specificity for unresectability was 0.80 (95% CI 0.40 to 0.96). The positive likelihood ratio and negative likelihood ratio were 4.3 (95% CI 1.0 to 18.6) and 0.2 (95% CI 0.0 to 0.8) respectively. At the mean pre-test probability of 60.5%, the post-test probability of unresectable disease for people with a positive EUS (EUS indicating unresectability) was 86.9% (95% CI 60.9% to 96.6%) and the post-test probability of unresectable disease for people with a negative EUS (EUS indicating resectability) was 20.0% (5.1% to 53.7%). This means that 13% of people (95% CI 3% to 39%) with positive EUS have potentially resectable cancer and 20% (5% to 53%) of people with negative EUS have unresectable cancer.

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