Davidson Tsetsegdemberel Bat-Ulzii, Yaghoobi Mohammad, Davidson Brian R, Gurusamy Kurinchi Selvan
University College London, London, UK.
Division of Gastroenterology, McMaster University and McMaster University Health Sciences Centre, 1200 Main Street West, Hamilton, ON, Canada.
Cochrane Database Syst Rev. 2017 Apr 7;4(4):CD012009. doi: 10.1002/14651858.CD012009.pub2.
The treatment of people with clinically significant postoperative pancreatic leaks is different from those without clinically significant pancreatic leaks. It is important to know the diagnostic accuracy of drain fluid amylase as a triage test for the detection of clinically significant pancreatic leaks, so that an informed decision can be made as to whether the patient with a suspected pancreatic leak needs further investigations and treatment. There is currently no systematic review of the diagnostic test accuracy of drain fluid amylase for the diagnosis of clinically relevant pancreatic leak.
To determine the diagnostic accuracy of amylase in drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection.
We searched MEDLINE, Embase, the Science Citation Index Expanded, and the National Institute for Health Research Health Technology Assessment (NIHR HTA) websites up to 20 February 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.
We included all studies that evaluated the diagnostic test accuracy of amylase in the drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection excluding total pancreatectomy. We planned to exclude case-control studies because these studies are prone to bias, but did not find any. At least two authors independently searched and screened the references produced by the search to identify relevant studies.
Two review authors independently extracted data from the included studies. The included studies reported drain fluid amylase on different postoperative days and measured at different cut-off levels, so it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative drain fluid amylase along with 95% confidence interval (CI) on each of the different postoperative days and measured at different cut-off levels.
A total of five studies including 868 participants met the inclusion criteria for this review. The five studies included in this review reported the value of drain fluid amylase at different thresholds and different postoperative days. The sensitivities and specificities were variable; the sensitivities ranged between 0.72 and 1.00 while the specificities ranged between 0.73 and 0.99 for different thresholds on different postoperative days. At the median prevalence (pre-test probability) of 15.9%, the post-test probabilities for pancreatic leak ranged between 35.9% and 95.4% for a positive drain fluid amylase test and ranged between 0% and 5.5% for a negative drain fluid amylase test.None of the studies used the reference standard of confirmation by surgery or by a combination of surgery and clinical follow-up, but used the International Study Group on Pancreatic Fistula (ISGPF) grade B and C as the reference standard. The overall methodological quality was unclear or high in all the studies.
AUTHORS' CONCLUSIONS: Because of the paucity of data and methodological deficiencies in the studies, we are uncertain whether drain fluid amylase should be used as a method for testing for pancreatic leak in an unselected population after pancreatic resection; and we judge that the optimal cut-off of drain fluid amylase for making the diagnosis of pancreatic leak is also not clear. Further well-designed diagnostic test accuracy studies with pre-specified index test threshold of drain fluid amylase (at three times more on postoperative day 5 or another suitable pre-specified threshold), appropriate follow-up (for at least six to eight weeks to ensure that there are no pancreatic leaks), and clearly defined reference standards (of surgical, clinical, and radiological confirmation of pancreatic leak) are important to reliably determine the diagnostic accuracy of drain fluid amylase in the diagnosis of pancreatic leak.
有临床意义的术后胰瘘患者的治疗与无临床意义的胰瘘患者不同。了解引流液淀粉酶作为检测有临床意义胰瘘的分诊试验的诊断准确性很重要，这样才能就是否对疑似胰瘘患者进行进一步检查和治疗做出明智的决定。目前尚无关于引流液淀粉酶诊断有临床相关性胰瘘的诊断试验准确性的系统评价。
确定术后48小时及以上引流液中淀粉酶对胰腺切除患者胰瘘诊断的准确性。
我们检索了截至2017年2月20日的MEDLINE、Embase、科学引文索引扩展版和英国国家卫生研究院卫生技术评估（NIHR HTA）网站。我们检索了纳入研究的参考文献以识别其他研究。我们没有根据语言、发表状态或数据是前瞻性还是回顾性收集来限制研究。我们还在MEDLINE和Embase中进行了“相关搜索”和“引用参考文献”搜索。
我们纳入了所有评估术后48小时及以上引流液中淀粉酶对胰腺切除（不包括全胰切除术）患者胰瘘诊断的诊断试验准确性的研究。我们计划排除病例对照研究，因为这些研究容易产生偏倚，但未找到此类研究。至少两名作者独立检索和筛选检索产生的参考文献以识别相关研究。
两名综述作者独立从纳入研究中提取数据。纳入研究报告了不同术后天数的引流液淀粉酶，并在不同的临界值水平进行测量，因此无法按计划使用双变量模型进行荟萃分析。我们报告了不同术后天数及不同临界值水平下引流液淀粉酶阳性和阴性的敏感性、特异性、检验后概率以及95%置信区间（CI）。
共有5项研究（包括868名参与者）符合本综述的纳入标准。本综述纳入的5项研究报告了不同阈值和不同术后天数的引流液淀粉酶值。敏感性和特异性各不相同；不同术后天数不同阈值下的敏感性在0.72至1.00之间，特异性在0.73至0.99之间。在15.9%的中位患病率（检验前概率）下，引流液淀粉酶试验阳性时胰瘘的检验后概率在35.9%至95.4%之间，引流液淀粉酶试验阴性时在0%至5.5%之间。没有一项研究使用手术或手术与临床随访相结合的确认参考标准，而是使用国际胰瘘研究组（ISGPF）的B级和C级作为参考标准。所有研究的总体方法学质量不明确或较高。
由于研究中的数据匮乏和方法学缺陷，我们不确定引流液淀粉酶是否应用作胰腺切除术后未经过筛选人群胰瘘检测的方法；并且我们判断用于诊断胰瘘的引流液淀粉酶的最佳临界值也不明确。进一步设计良好的诊断试验准确性研究，设定引流液淀粉酶的预先指定指标试验阈值（术后第5天为三倍或其他合适的预先指定阈值）、进行适当的随访（至少六至八周以确保无胰瘘）以及明确界定参考标准（胰瘘的手术、临床和放射学确认）对于可靠确定引流液淀粉酶在胰瘘诊断中的诊断准确性很重要。
