Background
The pancreas is an organ situated in the abdomen close to the junction of the stomach and small bowel. It secretes digestive juices which 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 during the major open operation the cancer is found to have spread within the abdomen, patients are referred for alternate treatments such as chemotherapy, which do not cure the cancer but may improve survival.
This major open abdominal operation can be avoided if the spread of cancer within the abdomen is known, called 'staging' the cancer. The minimum test used for staging is usually the computed tomography (CT) scan. However, CT scan can understage the cancer, that is it can underestimate the spread of cancer. Laparoscopy, a procedure whereby a small telescope is inserted inside the abdomen through a small (keyhole) surgical incision, can detect spread not identified on CT scanning. Different studies report different accuracy of laparoscopy in assessing whether the cancer can be removed. Our aim therefore was to find out the average diagnostic accuracy of laparoscopy for staging pancreatic and periampullary cancers considered to be removable after a CT scan. This review is an update of our previous review.
A glossary of terms is provided in Appendix 1.
Study characteristics
We performed a thorough literature search to identify studies published up to 15 May 2016. We identified 16 studies reporting information on 1146 people with pancreatic or periampullary cancers which were considered to be eligible for potentially curative surgery based on CT scan staging. These studies evaluated diagnostic laparoscopy and compared results of the procedure with the eventual diagnosis by the surgeon that the cancer was not resectable during major abdominal operation or examination under microscope.
Quality of evidence
All of the studies were of unclear or low methodological quality in one or more aspects, which may undermine the validity of our findings.
Key results
Of those people with what CT suggests seems to be a potentially surgically curable cancer, the percentage in whom more extensive cancer was found on further staging with diagnostic laparoscopy or laparotomy ranged between 17% and 82% across studies. The median percentage of people in whom cancer spread was not detected by CT scan was 41%. Adding staging laparoscopy to CT scan might decrease the number of people with unremovable disease undergoing unnecessary major operations to 20% compared to those who undergo unnecessary major operation after CT scan alone (41%). This means that using diagnostic laparoscopy could halve the rate of unnecessary major open operations in people undergoing major surgery for potentially surgically curable pancreatic cancer.
Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned.
Surgical resection is the only 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. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer.
To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016).
We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. 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.
Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone.
We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.
A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone.