Deng Yilei, He Sirong, Cheng Yao, Cheng Nansheng, Gong Jianping, Gong Junhua, Zeng Zhong, Zhao Longshuan
The First Affiliated Hospital of Zhengzhou University, Department of Hepatopancreatobiliary Surgery, No. 1, Jianshe East Road, Zhengzhou, Henan Province, China, 450000.
Chongqing Medical University, Department of Immunology, College of Basic Medicine, No. 1 Yixue Road, Chongqing, China, 450000.
Cochrane Database Syst Rev. 2020 Mar 11;3(3):CD009621. doi: 10.1002/14651858.CD009621.pub4.
Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants have been used in some centers to reduce postoperative pancreatic fistula. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2018.
To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.
We searched trial registers and the following biomedical databases: the Cochrane Library (2019, Issue 2), MEDLINE (1946 to 13 March2019), Embase (1980 to 11 March 2019), Science Citation Index Expanded (1900 to 13 March 2019), and Chinese Biomedical Literature Database (CBM) (1978 to 13 March 2019).
We included all randomised controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery.
Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs).
We included 12 studies involving 1604 participants in the review. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included seven studies involving 860 participants: 428 were randomised to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence) or length of hospital stay (MD 0.99 days, 95% CI -1.83 to 3.82; 371 participants; two studies; very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included four studies involving 393 participants: 186 were randomised to the fibrin sealant group and 207 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (16.7% versus 11.7%; RR 1.14, 95% CI 0.28 to 4.69; 199 participants; two studies; very low-quality evidence). We are uncertain whether fibrin sealants reduce postoperative mortality (0.5% versus 2.4%; Peto OR 0.26, 95% CI 0.05 to 1.32; 393 participants; four studies; low-quality evidence) or length of hospital stay (MD 0.01 days, 95% CI -3.91 to 3.94; 323 participants; three studies; very low-quality evidence). There is probably little or no difference in overall postoperative morbidity (52.6% versus 50.3%; RR 1.04, 95% CI 0.87 to 1.24; 323 participants; three studies; moderate-quality evidence) between the groups. We are uncertain whether fibrin sealants reduce reoperation rate (5.2% versus 7.7%; RR 0.74, 95% CI 0.33 to 1.66; 323 participants; three studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two studies involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (median 16 to 17 days versus 17 days; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study (169 participants; low-quality evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness.
AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.
术后胰瘘是胰腺切除术后最常见且可能危及生命的并发症之一。一些中心使用纤维蛋白封闭剂来降低术后胰瘘的发生率。然而，在胰腺手术中使用纤维蛋白封闭剂存在争议。这是对2018年发表的Cochrane系统评价的更新。
评估纤维蛋白封闭剂预防胰腺手术后胰瘘的安全性、有效性及潜在不良反应。
我们检索了试验注册库以及以下生物医学数据库：Cochrane图书馆（2019年第2期）、MEDLINE（1946年至2019年3月13日）、Embase（1980年至2019年3月11日）、科学引文索引扩展版（1900年至2019年3月13日）和中国生物医学文献数据库（CBM）（1978年至2019年3月13日）。
我们纳入了所有比较纤维蛋白封闭剂（纤维蛋白胶或纤维蛋白封闭剂贴片）与对照组（未使用纤维蛋白封闭剂或安慰剂）在接受胰腺手术患者中的随机对照试验。
两位综述作者独立确定纳入的试验，收集数据并评估偏倚风险。我们使用Review Manager 5进行荟萃分析。我们计算二分变量结局的风险比（RR）（或极罕见结局的Peto比值比（OR））以及连续变量结局的平均差（MD），并给出95%置信区间（CI）。
我们纳入了12项研究，共1604名参与者。在远端胰腺切除术后将纤维蛋白封闭剂应用于胰腺残端闭合加固：我们纳入了7项研究，共860名参与者：在远端胰腺切除术后，428名被随机分配至纤维蛋白封闭剂组，432名被分配至对照组。纤维蛋白封闭剂可能导致术后胰瘘发生率几乎无差异或差异极小（纤维蛋白封闭剂组为19.3%；对照组为20.1%；RR 0.96，95%CI 0.68至1.35；755名参与者；4项研究；低质量证据）。纤维蛋白封闭剂可能还会使术后死亡率几乎无差异或差异极小（0.3%对0.5%；Peto OR 0.52，95%CI 0.05至5.03；804名参与者；6项研究；低质量证据），或总体术后发病率几乎无差异或差异极小（28.5%对23.2%；RR 1.23，95%CI 0.97至1.58；646名参与者；3项研究；低质量证据）。我们不确定纤维蛋白封闭剂是否能降低再次手术率（2.0%对3.8%；RR 0.51，95%CI 0.15至1.71；376名参与者；2项研究；极低质量证据）或住院时间（MD 0.99天，95%CI -1.83至3.82；371名参与者；2项研究；极低质量证据）。这些研究未报告严重不良事件、生活质量或成本效益。在胰十二指肠切除术后将纤维蛋白封闭剂应用于胰腺吻合口加固：我们纳入了4项研究，共393名参与者：在胰十二指肠切除术后，186名被随机分配至纤维蛋白封闭剂组，207名被分配至对照组。我们不确定纤维蛋白封闭剂是否能降低术后胰瘘发生率（16.7%对11.7%；RR 1.14，95%CI 0.28至4.69；199名参与者；2项研究；极低质量证据）。我们不确定纤维蛋白封闭剂是否能降低术后死亡率（0.5%对2.4%；Peto OR 0.26，95%CI 0.05至1.32；393名参与者；4项研究；低质量证据）或住院时间（MD正负0.01天，95%CI -3.91至3.94；323名参与者；3项研究；极低质量证据）。两组之间总体术后发病率可能几乎无差异或差异极小（52.6%对50.3%；RR 1.04，95%CI 0.87至1.24；323名参与者；3项研究；中等质量证据）。我们不确定纤维蛋白封闭剂是否能降低再次手术率（5.2%对7.7%；RR 0.74，95%CI 0.33至1.66；323名参与者；3项研究，极低质量证据）。这些研究未报告严重不良事件、生活质量或成本效益。在胰十二指肠切除术后将纤维蛋白封闭剂应用于胰管闭塞：我们纳入了2项研究，共351名参与者：在胰十二指肠切除术后，188名被随机分配至纤维蛋白封闭剂组，163名被分配至对照组。纤维蛋白封闭剂可能导致术后死亡率几乎无差异或差异极小（8.4%对6.1%；Peto OR 1.41，95%CI 0.63至3.13；351名参与者；2项研究；低质量证据）或住院时间（中位数16至17天对17天；351名参与者；2项研究；低质量证据）。我们不确定纤维蛋白封闭剂是否能降低总体术后发病率（32.0%对27.6%；RR 1.16，95%CI 0.67至2.02；351名参与者；2项研究；极低质量证据），或再次手术率（13.6%对16.0%；RR 0.85，95%CI 0.52至1.41；351名参与者；2项研究；极低质量证据）。一项研究（169名参与者；低质量证据）报告了严重不良事件：在胰管闭塞应用纤维蛋白封闭剂时，更多参与者在3个月随访时发生糖尿病（纤维蛋白封闭剂组为33.7%，对照组为10.8%；29名参与者对9名参与者）以及在12个月随访时发生糖尿病（纤维蛋白封闭剂组为33.7%，对照组为14.5%；29名参与者对12名参与者）。这些研究未报告术后胰瘘、生活质量或成本效益。
基于目前可得证据，纤维蛋白封闭剂可能对接受远端胰腺切除术患者的术后胰瘘几乎无影响。纤维蛋白封闭剂对预防胰十二指肠切除术后胰瘘的效果尚不确定。
