Periampullary cancer develops near the ampulla of Vater (National Cancer Institute 2011a). This 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. Pancreaticoduodenectomy is the main treatment for cancers arising in the head of the pancreas, ampulla, and second part of the duodenum. Surgical resection is generally considered the only treatment that can cure pancreatic cancer. However, only 15% to 20% of patients with pancreatic cancers undergo potentially curative resection (Conlon 1996; Engelken 2003; Michelassi 1989; Shahrudin 1997; Smith 2008). In all other patients the cancers are not resected because of infiltration of local structures, disseminated disease, or because the patient is deemed unfit to undergo major surgery. Computed tomography (CT scan) (National Cancer Institute 2011b) is generally used for staging pancreatic and periampullary cancers. Despite undergoing routine CT scanning to stage the disease (Mayo 2009) a substantial proportion of patients (approximately 10% to 25%) undergo unnecessary laparotomy (opening the abdomen using a large incision) with lack of curative resectability identified only during the laparotomy (Lillemoe 1999; Mayo 2009). Laparoscopy can be used to detect metastatic disease in patients with periampullary cancer.
Target condition being diagnosed
Inability to perform curative resectability of pancreatic and periampullary cancer ('unresectable' cancers)
Diagnostic laparoscopy involves the use of a laparoscope (a telescope that can be inserted into the abdominal cavity through a key hole incision) to visualise and explore the abdominal organs. This is also called staging laparoscopy. It is used following initial staging by CT scanning. Any spread of cancer to the liver, peritoneum, or adjacent structures can be visualised during diagnostic laparoscopy. A biopsy of the suspicious lesion can be performed and the biopsy specimen can be examined under the microscope to confirm that the suspicious lesion is spread of cancer.
There is no standard algorithm currently available for assessing the resectability of pancreatic and periampullary cancers, with different clinicians following their own algorithms based on either their clinical experience or what they were taught. Currently, almost all algorithms include a CT scan (National Cancer Institute 2011b) as one of the tests. CT may be the only test performed before laparotomy. Other tests such as diagnostic laparoscopy, positron emission tomography (PET scanning), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS) may be used in addition to CT scan to assess resectability. The possible clinical pathway in the staging of pancreatic cancers is shown in Figure 1. The accuracy of all of these various tests and the CT scanning are being assessed in another review (Gurusamy 2013).
|Figure 1. Clinical pathway.|
PET: positron emission tomography
MRI: magnetic resonance imaging
EUS: endoscopic ultrasound
The minimum prior test should be CT and the cancer should be resectable with curative intent on the basis of the CT scan to be included in this review. Other tests such as PET scanning, MRI, or EUS might be used in addition to CT scanning to assess resectability prior to diagnostic laparoscopy. Patients were included in this review irrespective of whether they underwent these tests prior to diagnostic laparoscopy.
Role of index test(s)
Diagnostic laparoscopy can be considered as an add-on test to the CT scan prior to laparotomy done with the intention of performing a potentially curative resection.
Other tests such as PET scanning, laparoscopic ultrasound, or EUS may be used as alternative tests to diagnostic laparoscopy in patients considered to have CT resectable pancreatic and periampullary cancer. As mentioned earlier, PET scanning and EUS may also be used prior to diagnostic laparoscopy. Laparoscopic ultrasound may be used in combination with diagnostic laparoscopy and the strategy for determining test positivity of the combination may be either test positive or both tests positive.
Diagnostic laparoscopy allows internal visualisation of the abdomen and can detect any peritoneal spread of the cancer or the involvement of any adjacent structures. A biopsy and histopathological examination of any suspicious lesion can be performed and an unnecessary laparotomy to attempt curative resection can be avoided. If this add-on test can identify unresectable cancers without laparotomy, it might decrease the costs and morbidity associated with unnecessary laparotomy. Currently there is no Cochrane review assessing the diagnostic accuracy of diagnostic laparoscopy in the assessment of the curative resectability of pancreatic and periampullary cancers.
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 planned to explore the following sources of heterogeneity.
- Full text publications versus abstracts (this can give a clue about publication bias since there may be an association between the results of the study and the study reaching full publication status (Eloubeidi 2001).
- Prospective studies versus retrospective studies.
- Proportion of patients with pancreatic cancer, ampullary cancer, and bile duct cancers (although classified as periampullary cancers they each have a different prognosis) (Klempnauer 1995). The additional value of diagnostic laparoscopy may be different because of the extent of spread in these different types of periampullary cancers.
- Procedures performed under the same anaesthetic versus procedures performed under a different anaesthetic (there are likely to be differences in the histopathological examinations since the former procedure is associated with frozen section biopsy while the latter procedure is likely to be associated with paraffin section). Paraffin section is considered the gold standard in identifying cancer. Frozen sections can be associated with false negative results (Yeo 2002). However, frozen section results are always confirmed by paraffin section histological examinations.
- Different definitions for resectable cancer on laparotomy. Different surgeons may consider cancer unresectable differently i.e. different surgeons will have different criteria for unresectability on laparotomy (other than the consensus criteria for resectability). For example, one surgeon may judge that the cancer is unresectable on laparotomy because of the involvement of the vessel and consider the reference standard to be positive. This will result in a false negative result for laparoscopy. Another surgeon may judge the same cancer to be resectable despite the involvement of the vessel and proceed with resection. The reference standard will be negative in this situation resulting in a true negative result for laparoscopy. This might have an intrinsic threshold effect.
- Additional pre-tests performed (besides CT scan). This can alter the pre-test probability of unresectability and can help in the assessment of the additional value of diagnostic laparoscopy under various situations.
Criteria for considering studies for this review
Types of studies
We included studies that evaluated the accuracy of diagnostic laparoscopy in the appropriate patient population (see below) irrespective of language or publication status, or whether data were collected prospectively or retrospectively. However, we excluded case reports which did not provide sufficient diagnostic test accuracy data. We also excluded case-control studies because case-control studies are prone to bias (Whiting 2011).
Patients about to undergo curative resection for pancreatic and periampullary cancer and found to have no contraindications (such as metastatic disease) for curative resection on CT scan, and who are anaesthetically fit to undergo major surgery.
We included only diagnostic laparoscopy in which histopathological confirmation of metastatic spread was obtained on a paraffin section.
The target conditions were unresectable pancreatic and periampullary cancers, that is diagnostic laparoscopy is considered a positive test if the pancreatic or periampullary cancer was unresectable. In these cancers it is not possible to perform curative resectability. There are no uniform criteria for resectability of pancreatic and periampullary cancer. Consensus exists for the definition of borderline resectable cancers (Abrams 2009). Therefore, where there is less tissue involvement than in a borderline resectable cancer the tumour can be considered as resectable. We accepted any criteria of resectability used by the study authors and acknowledge that this could potentially create a threshold effect. In general, the cancer would not be resected if liver or peritoneal metastases were noted, or if the cancer had invaded important adjacent blood vessels that are beyond the criteria for borderline resectable cancers, for example, greater than 180 ° involvement of the superior mesenteric artery.
Confirmation of liver or peritoneal involvement by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted only paraffin section histology as the reference standard. In clinical practice, depending on the urgency of the results, a frozen section biopsy may be done to obtain immediate results. However, this is always confirmed by subsequent paraffin section histology (which can take several days) because frozen section biopsy is not as reliable as paraffin section histology. We also accepted the surgeon's judgement of unresectability at laparotomy when biopsy confirmation was not possible. For example, if the tumour has invaded the adjacent blood vessels the surgeon may not resect the tumour because of the danger posed by resecting part of a large blood vessel, and so biopsy confirmation cannot be obtained.
Diagnostic laparoscopy results versus reference standard results
A schematic diagram of the results of diagnostic laparoscopy against those of histopathology or laparotomy is shown in Figure 2. Positive histopathology of a biopsy taken during diagnostic laparoscopy confirms the presence of cancer (true positive). Thus, the index test and the reference standard are one and the same if there is positive histopathology after laparoscopy. As a result, false positives are not possible and there is no sampling error associated with specificity because it is by definition equal to 1. If the histopathology is negative, the surgeon will perform a laparotomy. The cancer may be resectable with curative intent (true negative) or may not be resectable with curative intent (false negative) based on histopathological confirmation or the surgeon's judgement of unresectability on laparotomy if biopsy confirmation cannot be obtained.
|Figure 2. Schematic diagram indicating how true positive, false negative, and true negative test results were determined.|
Search methods for identification of studies
We included all studies irrespective of the language of publication and publication status. If non-English articles were found, we obtained translations.
We searched the following databases until 13 September 2012.
- Cochrane Register of Diagnostic Accuracy Tests (latest issue) (Appendix 1).
- Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (latest issue) (Appendix 1).
- MEDLINE via PubMed (January 1946 to present) (Appendix 2).
- EMBASE via OvidSP (January 1947 to present) (Appendix 3).
- Science Citation Index Expanded (January 1980 to present) (Appendix 4).
Searching other resources
We searched the references of the included studies to identify additional studies. We also searched for articles related to the included studies by performing the 'related search' function in MEDLINE (PubMed) and EMBASE (OvidSP) and a 'citing reference' search (by searching the articles which cited the included articles) (Sampson 2008) in Science Citation Index Expanded and EMBASE (OvidSP).
Data collection and analysis
Selection of studies
Two authors (VA and KG or AK) independently searched the references to identify relevant studies. We obtained the full texts for references considered relevant by at least one of the authors. Two authors screened the full text papers against the inclusion criteria. Any differences in study selection were arbitrated by BRD.
Data extraction and management
Two authors independently extracted the following data from each included study, and any differences were resolved by discussion with BRD.
- First author.
- Year of publication.
- Study design (prospective or retrospective; cross-sectional studies or randomised clinical trials).
- Inclusion and exclusion criteria for individual studies.
- Total number of patients.
- Number of females.
- Average age of the participants.
- Type of cancer (i.e. head and neck of pancreas, body and tail of pancreas, ampullary cancers, cancer of the lower end of the bile duct).
- Criteria for unresectability at diagnostic laparoscopy (index test) and at laparotomy (reference standard).
- Pre-operative tests carried out prior to diagnostic laparoscopy.
- Description of the index test.
- Reference standard.
- Number of true positives, true negatives, and false negatives.
- Complications of diagnostic laparoscopy.
The unit of analysis was the patient, meaning that if multiple metastases were found in a patient with a negative index test the number of false negatives was considered to be one. This is because it is the presence rather than the number of metastases which is important in determining the curative resectability of patients. We considered patients with uninterpretable diagnostic laparoscopy results (no matter the reason given for lack of interpretation) as negative for the test since in clinical practice laparotomy would be carried out on these patients. However, such patients were included in the analysis only if the results of laparotomy were available. Further information was sought from study authors if necessary.
Assessment of methodological quality
Two authors (VA and KG) independently assessed study quality using the QUADAS-2 assessment tool (Whiting 2006; Whiting 2011). Any differences were resolved by KG or BRD. The criteria used to classify the different studies are shown in Table 1. We considered studies which were classified as 'low risk of bias' and 'low concern' in all the domains as studies with high methodological quality.
Statistical analysis and data synthesis
The index test used was diagnostic laparoscopy with biopsy and histopathological confirmation. For the reason mentioned earlier, false positives were not possible. Therefore we performed meta-analysis of only sensitivities by removing the logit specificity and correlation parameters from the standard bivariate model (Reitsma 2005) thus simplifying the model to a univariate random-effects logistic regression model. The negative likelihood ratio was derived from the model by using the estimated summary sensitivity and assuming a specificity of 1. The analysis was done using the NLMIXED procedure in SAS version 9.2 (SAS Institute Inc., Cary, North Carolina, USA). The median pre-test probability of unresectability was calculated from the pre-test probabilities of the included studies. The proportion of patients classified as having resectable disease by CT scanning and diagnostic laparoscopy who were actually found to be unresectable at laparotomy (post-test probability) was calculated using the median pre-test probability and the negative likelihood ratio (see Appendix 6 for details). The difference in the unresectability proportions (post-test probability minus pre-test probability) gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone.
Investigations of heterogeneity
We planned to explore heterogeneity by using the different sources of heterogeneity as covariate(s) in the regression model. However, this was not possible because the information was either not available or was the same in all the studies.
We did not plan any sensitivity analyses.
Results of the search
We identified a total of 15,236 references through the electronic searches of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Controlled Trials Register and CENTRAL (n = 85), MEDLINE (n = 3824), EMBASE (n = 8278), and Science Citation Index Expanded (n = 3049). Figure 3 shows the flow of references through the selection process. We excluded 4180 duplicates and clearly irrelevant references through reading the abstracts. We retrieved 202 references for further assessment. No references were identified through scanning reference lists of the identified studies. Of the 202 references, we excluded 185 for the reasons listed in the table Characteristics of excluded studies. This resulted in inclusion of 17 references of 15 studies.
|Figure 3. Flow diagram of study selection.|
Methodological quality of included studies
|Figure 4. Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies.|
|Figure 5. Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study.|
In most studies there was a high risk of bias regarding the selection of patients (Ahmed 2006; Arnold 1999; Arnold 2001a; Brooks 2002; Contreras 2009; John 1995; Kishiwada 2002; Lavy 2012; Menack 2001; Merchant 1998; Reddy 1999; Reed 1997; Shah 2008; Warshaw 1986). This was because the studies did not explicitly state whether a consecutive or random sample of patients were recruited or whether they had made inappropriate exclusions. Only one study had low risk of bias and low applicability concerns regarding the selection of patients (Fernandez-Castillo 1995).
There were no risk of bias issues or concerns regarding applicability of the index test in any of the studies, as was anticipated ( Table 1).
As anticipated, it proved impossible to determine whether an appropriate reference standard was used. This is because even in the presence of predefined criteria for unresectability it may not be ethical to biopsy and confirm that the tumour has invaded the blood vessels because of the risk of major bleeding. Thus it was not possible to determine whether the cancer was truly unresectable. None of the studies reported whether the margins of the resected lesions were clear of cancer. Thus it was not possible to determine whether the cancer was truly resectable with curative intent.
None of the studies reported the time interval between diagnostic laparoscopy and laparotomy. In addition, many studies had excluded some patients inappropriately. Therefore, all the studies were of unclear or high risk of bias in the flow and timing domain.
All the included studies assessed pancreatic or periampullary cancer. The age of patients in the included studies ranged between 15 and 87 years. Studies that provided demographic details of patients reported roughly equal numbers of males and females. Several studies included only patients with pancreatic cancer (Ahmed 2006; Arnold 2001a; Contreras 2009; Fernandez-Castillo 1995; Kishiwada 2002; Lavy 2012; Warshaw 1986) and one study (Brooks 2002) included only patients with periampullary malignancies. The remaining studies did not provide information regarding the specific type of cancer they considered.
The details of the CT scan; other tests that the patients underwent in addition to the CT scan; probability of CT resectable disease identified as unresectable by diagnostic laparoscopy or laparotomy (pre-test probability); reasons for CT resectable disease identified as unresectable by diagnostic laparoscopy; probability of CT and diagnostic laparoscopy resectable disease identified as unresectable at laparotomy (post-test probability); and the reasons for CT and diagnostic laparoscopy resectable disease identified as unresectable at laparotomy are all shown in Table 2.
The pre-test probability of unresectability (due to distant metastases or local infiltration) after CT scanning ranged from 17% to 82% in the included studies. The median pre-test probability was 40.3%, meaning that a patient that was said to be resectable on CT scanning still had a 40% chance that their cancer would be unresectable. Visual inspection of the data in Table 2 did not suggest a relationship between the type of CT scan (such as helical CT or multi-detector row CT, with or without a pancreatic protocol) or date of publication and the pre-test probability of unresectable disease.
The summary estimate of sensitivity was 68.7% (95% CI 54.3 to 80.2) and the summary negative likelihood ratio was 0.31 (95% CI 0.21 to 0.48). Using the median pre-test probability of unresectable disease of 0.403, the post-test probability of unresectable disease for patients with a negative test result was 0.17 (95% CI 0.12 to 0.24). This means that if a patient is said to have resectable disease after diagnostic laparoscopy (and a CT scan) there is a 17% chance that their cancer will be unresectable. The post-test probability of unresectable disease is shown at different pre-test probabilities of unresectable disease in Figure 6.
|Figure 6. Post-test probability of unresectability for various pre-test probabilities.|
None of the studies reported any complications related to diagnostic laparoscopy. In some instances diagnostic laparoscopy provided an inconclusive result, that is it was unclear whether the patient had resectable or unresectable disease. Seven studies reported dropout rates of: 37.3% (Ahmed 2006), 29.8% (Arnold 1999), 67.5% (Contreras 2009), 4.4% (Fernandez-Castillo 1995), 10.6% (Merchant 1998), 1.0% (Reddy 1999), and 61.2% (Shah 2008). In three of these studies the patients underwent laparotomy directly (Ahmed 2006; Contreras 2009; Shah 2008) and there was no indication of the selection criteria used for patients who had diagnostic laparoscopy. The other studies did not report dropout rates.
A subgroup analysis of studies that included only patients with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The summary negative likelihood ratio was 0.32 (95% CI 0.15 to 0.68). The median pre-test probability of unresectability was 40.0% in this subgroup of studies. Using this pre-test probability, the post-test probability of unresectable disease after negative diagnostic laparoscopy was 0.18 (95% CI 0.92 to 0.31).
A post hoc meta-regression of studies published before and after the year 2000 was also performed. This was to test whether the sensitivity of diagnostic laparoscopy was different in the last decade, because major technological innovations in CT scans such as helical CT scans and multi-slice CT scans became widely available in the last decade. The likelihood ratio test comparing the model with and without this covariate gave a P value of 0.44, suggesting no evidence of a statistically significant difference in sensitivity between studies published before or after the year 2000.
An inconsistency was found in one study (Kishiwada 2002) between the results reported in the main text of the study and a flow diagram which summarised the results. We investigated the effect of this inconsistency by conducting a sensitivity analysis, which showed no change in the estimates of the summary sensitivity and the confidence intervals. In another sensitivity analysis, we imputed missing data as false negative results (that is diagnostic laparoscopy incorrectly classified unresectable disease as resectable in all the missing patients). The summary sensitivity from this analysis was 48.4% (95% CI 32.9% to 64.2%) and the summary negative likelihood ratio was 0.52 (95% CI 0.38 to 0.71), which corresponded to a post-test probability of 0.26 (95% CI 0.20 to 0.32) using a pre-test probability of 0.403.
Summary of findings
Summary of main results
The results are summarised in Summary of findings. The addition of diagnostic laparoscopy to CT scanning decreases the probability of unresectable disease from 40% to 17%. This means that for every 100 patients who receive a CT scan followed by diagnostic laparoscopy, 23 patients (40 minus 17) will avoid major laparotomy compared to with CT scanning alone. Although this review included studies which were more than 10 years old, with improvements in CT scanning possible over this period, the probability of unresectability was high (63.2%) even after multi-detector row CT using a pancreatic protocol ( Table 2). Diagnostic laparoscopy can either be performed as a separate procedure or immediately prior to major laparotomy as part of a larger procedure. These two different approaches have distinct advantages and disadvantages. The advantages of performing diagnostic laparoscopy as part of a larger procedure are that the patient needs only one hospital admission and one general anaesthetic. However, if the patient is diagnosed as having unresectable disease at laparoscopy and the subsequent laparotomy is then cancelled it means that operation theatre time is wasted. It is also not possible to use paraffin section, the gold standard test, to confirm a histological diagnosis of cancer if diagnostic laparoscopy is undertaken as part of a larger procedure. If laparoscopy is performed as a separate diagnostic procedure the patient must undergo the burden of two separate hospital admissions and anaesthetics, but no operation theatre time will be wasted if they are found to have unresectable disease. The time delay between the two separate procedures also allows the use of paraffin sections.
No complications related to diagnostic laparoscopy were found in this systematic review, however the literature reports an injury rate of 0.23% involving major blood vessels or the bowel (Azevedo 2009). This indicates that diagnostic laparoscopy should only be performed by appropriately trained healthcare professionals with expertise in the conduct of diagnostic laparoscopy and biopsy during diagnostic laparoscopy.
Strengths and weaknesses of the review
A strength of this review is that no restrictions were placed on the language of publication and we conducted a comprehensive search. The use of search filters was avoided and we undertook additional searches to find related articles. We also performed a citation search. Therefore, we minimised the risk of missing relevant studies. Little is known about the mechanisms of publication bias for diagnostic accuracy studies and so it is not possible to estimate the impact of unpublished studies on our findings. Nevertheless, the studies included in this systematic review are likely to be the majority of studies that provide evidence on this topic. Another strength of this review is that we used a recommended approach for meta-analysis.
Our review has some weaknesses. Firstly, our findings are based on studies with low methodological quality and there was considerable between study heterogeneity. There were between study differences in the conduct and interpretation of diagnostic laparoscopy (in terms of what constitutes a suspicious lesion) and differences in the assessment of resectability on laparotomy. Despite the observed differences in the conduct and interpretation of diagnostic laparoscopy, diagnostic laparoscopy appeared to decrease the number of unnecessary laparotomies in 14 of the 15 included studies. With regards to methodological quality, the presence of selection bias may raise doubts about the applicability of our findings in clinical practice. Secondly, determination of unresectability on laparotomy relies on the judgement of individual surgeons, which may not have been appropriate in some of the studies. This could have caused an error in the estimation of diagnostic accuracy. Thirdly, an inappropriate delay between diagnostic laparoscopy and laparotomy can result in patients who had previously resectable cancer developing unresectable cancer because of local or distant spread. This will underestimate the accuracy of diagnostic laparoscopy. Fourthly, inappropriate exclusion of patients is likely to result in an error in the estimation of diagnostic accuracy if the excluded patients had low likelihood of unresectability or high likelihood of unresectability. We performed a sensitivity analysis imputing the results according to the worst case scenario, that is as false negatives. As mentioned earlier, indeterminate results at diagnostic laparoscopy will result in the patients undergoing laparotomy. Despite the sensitivity analysis done by imputing results for excluded patients as false negatives, there was still a considerable reduction in the number of unnecessary laparotomies due to the use of diagnostic laparoscopy (40% to 26%).
We were able to identify one previous systematic review on this topic (Chang 2009). Despite the inclusion of studies in which histopathological confirmation of suspicious lesions was not obtained, and the lack of meta-analysis on the diagnostic accuracy of diagnostic laparoscopy, the authors of the review suggested that diagnostic laparoscopy decreases unnecessary laparotomy by 4% to 36% and that diagnostic laparoscopy has a role in staging pancreatic cancer (Chang 2009). We agree broadly with the conclusions of the authors of the identified systematic review (Chang 2009).
Applicability of findings to the review question
This review is only applicable to patients with pancreatic and periampullary cancer who have had a CT scan which demonstrated resectable disease prior to diagnostic laparoscopy. This review is also applicable only when the interval between diagnostic laparoscopy and laparotomy is sufficient to obtain histopathology results but not too long for the cancer to spread. Diagnostic laparoscopy appears to be beneficial in avoiding unnecessary laparotomies, and the morbidity associated with diagnostic laparoscopy is low. Cost-effectiveness needs to be formally assessed to inform clinical and policy decision making in state funded health care.
Implications for practice
Although the methodological quality of the evidence was limited, diagnostic laparoscopy appears to be useful in decreasing the proportion of patients with pancreatic and periampullary cancer that were found to have resectable disease on CT scanning who will undergo unnecessary laparotomy.
Implications for research
We thank the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group, the UK Support Unit for Diagnostic Test Accuracy (DTA) Reviews, and the DTA editorial team for their advice in the preparation of this review.
- Top of page
- Authors' conclusions
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Differences between protocol and review
- Index terms
Presented below are all the data for all of the tests entered into the review.
Appendix 1. Cochrane Register of Diagnostic Test Accuracy Studies and CENTRAL search strategy
#1 ((ampulla near/2 vater*) or ampullovateric or (papilla near/2 vater*) or periampulla* OR peri-ampulla* OR choledoch* or alcholedoch* or bile duct* or biliary or cholangio* or gall duct or duoden* or small bowel or small intestin* or enter* or pancrea*)
#2 (carcin* or cancer* or neoplas* or tumour* or tumor* or cyst* or growth* or adenocarcin* or malign*)
#3 (#1 AND #2)
#4 (pancreatect* OR pancreaticojejunost* OR pancreaticogastros* OR pancreaticoduodenect* OR duodenopancreatectom*)
#5 (#3 OR #4)
#6 (laparoscop* or peritoneoscop* or celioscop* or coelioscop*)
#7 (#5 AND #6)
Appendix 2. MEDLINE search strategy
(((((ampulla vateri[tiab] OR "Ampulla of Vater" [Mesh] OR ampullovateric[tiab] OR papilla vateri[tiab] OR vater papilla[tiab] OR vater ampulla[tiab] OR peri-ampull*[tiab] OR periampull*[tiab] OR choledoch*[tiab] OR alcholedoch*[tiab] OR bile duct*[tiab] OR biliary[tiab] OR cholangio*[tiab] OR gall duct[tiab] OR duodenum[tiab] OR duodenal[tiab] OR duoden*[tiab] OR small bowel[tiab] OR small instestin*[tiab] OR enteral[tiab] OR enteric[tiab] OR enter*[tiab] OR pancreatic[tiab] OR pancreato*[tiab] OR pancreas*[tiab]) AND (carcinoma[tiab] OR carcinomas[tiab] OR carcin*[tiab] OR cancer*[tiab] OR neoplas*[tiab] OR tumor[tiab] OR tumors[tiab] OR tumorous[tiab] OR tumour*[tiab] OR tumor*[tiab] OR cyst[tiab] OR cysts[tiab] OR cystic[tiab] OR cyst*[tiab] OR growth*[tiab] OR adenocarcin*[tiab] OR malignant[tiab] OR malignancy[tiab])) OR "Duodenal Neoplasms"[Mesh] OR "Pancreatic Neoplasms"[Mesh] OR "Common Bile Duct Neoplasms"[Mesh]) AND (surger*[tiab] OR operat*[tiab] OR resection*[tiab] OR surgical*[tiab] OR Surgical Procedures, Operative[MeSH] OR General Surgery[MeSH])) OR (pancreatect*[tiab] OR pancreaticojejunost*[tiab] OR pancreaticogastros*[tiab] OR pancreaticoduodenect*[tiab] OR duodenopancreatectom*[tiab] OR Pancreatectomy[MeSH] OR Pancreaticojejunostomy[MeSH] OR Pancreaticoduodenectomy[MeSH])) AND (laparoscop*[tiab] OR peritoneoscop*[tiab] OR celioscop*[tiab] OR coelioscop*[tiab] OR "Laparoscopy"[Mesh])
Appendix 3. EMBASE search strategy
1 ((ampulla vateri or ampullovateric or papilla vateri or vater papilla or vater ampulla or periampull* or peri-ampull* or choledoch* or alcholedoch* or bile duct* or biliary or cholangio* or gall duct or duoden* or small bowel or small intestin* or enter* or pancrea*) and (carcin* or cancer* or neoplas* or tumour* or tumor* or cyst* or growth* or adenocarcin* or malign*)).ti,ab.
2 exp duodenum cancer/ or Vater papilla tumor/ or exp pancreas cancer/ or exp bile duct tumor/
3 1 or 2
4 (surger* or surgical* or operat* or resection*). ti,ab.
5 exp Surgery/
6 4 or 5
7 3 and 6
8 (pancreatect* OR pancreaticojejunost* OR pancreaticogastros* OR pancreaticoduodenect* OR duodenopancreatectom*). ti,ab.
9 exp pancreas surgery/
10 7 or 8 or 9
11 (laparoscop* or peritoneoscop* or celioscop* or coelioscop*). ti,ab.
12 laparoscopy/ or laparoscopic surgery/
13 11 or 12
14 10 and 13
Appendix 4. Science Citation Index search strategy
#1 TS=(((ampulla vateri or ampullovateric or papilla vateri or vater papilla or vater ampulla or periampull* or peri-ampull* or choledoch* or alcholedoch* or bile duct* or biliary or cholangio* or gall duct or duoden* or small bowel or small intestin* or enter* or pancrea*) and (carcin* or cancer* or neoplas* or tumour* or tumor* or cyst* or growth* or adenocarcin* or malign*)))
#2 TS=(operat* OR surger* OR surgical* OR resection*)
#3 #1 AND #2
#4 TS=(pancreatect* OR pancreaticojejunost* OR pancreaticogastros* OR pancreaticoduodenect* OR duodenopancreatectom*)
#5 #3 OR #4
#6 TS=(laparoscop* or peritoneoscop* or celioscop* or coelioscop*)
#7 #5 AND #6
Appendix 5. SAS code for analysis
input Study_id TP FP FN TN;
1 9 0 4 24
2 11 0 4 18
3 14 0 5 42
4 13 0 12 119
5 7 0 3 15
6 27 0 52 30
7 14 0 14 12
8 10 0 0 6
9 4 0 5 18
10 104 0 18 181
11 29 0 8 61
12 2 0 7 2
13 11 0 1 7
14 14 0 3 23
15 5 0 9 28
/* Modify the dataset for the analysis */
sens=1; spec=0; true=tp; n=tp+fn; output;
sens=0; spec=1; true=tn; n=tn+fp; output;
/* Ensure that both records for a study are clustered together */
proc sort data=dt;
by study_id ;
ods output ParameterEstimates=pet4 FitStatistics=fitt4 additionalestimates=addest4;
/* Run random effects logistic regression model for sensitivity only*/
proc nlmixed data=dt tech=quanew lis=5 qpoints=10;
parms msens=2 s2usens=0 ;
p = exp(logitp)/(1+exp(logitp));
model true ˜ binomial(n,p);
random usens ˜ normal(,[s2usens]) subject=study_id out=randeffs;
/* logLR based on spec=1 */
estimate 'logLR-' log((1-(exp(msens)/(1+exp(msens))))) ;
/* Obtain summary sens and spec from the model 4 */
if parameter = 'msens' then name = 'Sensitivity';
if parameter = 'msens' then summary=100 * exp(estimate)/(1 + exp(estimate));
if parameter = 'msens' then summlower=100 * exp(lower)/(1 + exp(lower));
if parameter = 'msens' then summupper=100 *exp(upper)/(1 + exp(upper));
/* Obtain summary LR- */
Appendix 6. Calculation of post-test probability of unresectable disease for patients with a negative test result
The post-test probability of unresectable disease for patients with a negative test result can be calculated from the pre-test probability of unresectable disease and the negative likelihood ratio. The calculation using the median pre-test probability from the included studies, as an example, is shown below.
Pre-test probability) = 0.403
Pre-test odds = Pre-test probability/(1-Pre-test probability) = 0.403/0.597 = 0.675
Post-test odds of negative test = Post-test odds * negative likelihood ratio = 0.675 * negative likelihood ratio
Post-test probability of unresectable disease for patients with a negative test result = Post-test odds/(1+Post-test odds)
Appendix 7. Glossary of Terms
Sensitivity - Proportion of diseased individuals correctly identified as having the disease by the index test True positives /(True positives + False negatives)
Specificity - Proportion of disease-free individuals correctly identified as being disease-free by the index test–True negatives/(False positives +True negatives)
Index test - The diagnostic test being evaluated. In this review the index test is diagnostic laparoscopy after CT scanning
Target condition - The disease or condition to be diagnosed. In this review the target condition is unresectable pancreatic and periampullary cancer
Reference standard - The test that is accepted as the best available to classify the target condition correctly in a particular setting. In this review the reference standard is biopsy with histolopathological confirmation after diagnostic laparascopy or laparatomy, or the surgeon's judgement of unresectability at laparotomy when biopsy confirmation was not possible
QUADAS - A tool for assessing the methodological quality of diagnostic accuracy studies in terms of risk of bias and applicability to the review question. The assessment parameters are described in more detail in the main text of the review
Last assessed as up-to-date: 13 September 2012.
Contributions of authors
VB Allen selected studies for inclusion, extracted the data, and wrote the draft of the review. KS Gurusamy wrote the protocol, selected studies for inclusion, and extracted the data and critically commented on the review. Y Takwoingi helped in the statistical analysis and critically commented on the review. A Kalia selected the studies for inclusion and extracted the data for some of the studies. BR Davidson critically commented on the review.
Declarations of interest
Sources of support
- University College London, UK.This was part of a BSc project for University College London. Funding was available for obtaining the full texts of articles.
- None, Other.
Differences between protocol and review
The QUADAS tool was replaced by the QUADAS-2 tool.
The software used for meta-analysis was different from the one stated in the protocol.
The median pre-test probability rather than the pre-test probability calculated by a meta-analysis of proportions was used to calculate the post-test probability.
Medical Subject Headings (MeSH)
*Ampulla of Vater; *Unnecessary Procedures; Common Bile Duct Neoplasms [pathology; radiography; *surgery]; Laparoscopy [*methods]; Laparotomy [*utilization]; Neoplasm Staging [*methods]; Pancreatic Neoplasms [*pathology; radiography; *surgery]; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed
MeSH check words