Gong Junhua, He Sirong, Cheng Yao, Cheng Nansheng, Gong Jianping, Zeng Zhong
Organ Transplant Center, First Affiliated Hospital of Kunming Medical University, No. 295, Xi Chang Road, Kunming, Yunnan, China, 650032.
Cochrane Database Syst Rev. 2018 Jun 23;6(6):CD009621. doi: 10.1002/14651858.CD009621.pub3.
Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2016.
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 (2018, Issue 4), MEDLINE (1946 to 12 April 2018), Embase (1980 to 12 April 2018), Science Citation Index Expanded (1900 to 12 April 2018), and Chinese Biomedical Literature Database (CBM) (1978 to 12 April 2018).
We included all randomized 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 11 studies involving 1462 participants in the review.Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomyWe included seven studies involving 860 participants: 428 were randomized 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). There is probably little or no difference in length of hospital stay between the groups (12.1 days versus 11.4 days; MD 0.32 days, 95% CI -1.06 to 1.70; 755 participants; four studies; moderate-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 pancreaticoduodenectomyWe included three studies involving 251 participants: 115 were randomized to the fibrin sealant group and 136 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (1.6% versus 6.2%; RR 0.25, 95% CI 0.01 to 5.06; 57 participants; one study; very low-quality evidence). Fibrin sealants may lead to little or no difference in postoperative mortality (0.1% versus 0.7%; Peto OR 0.15, 95% CI 0.00 to 7.76; 251 participants; three studies; low-quality evidence) or length of hospital stay (12.8 days versus 14.8 days; MD -1.58 days, 95% CI -3.96 to 0.81; 181 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (33.7% versus 34.7%; RR 0.97, 95% CI 0.65 to 1.45; 181 participants; two studies; very low-quality evidence), or reoperation rate (7.6% versus 9.2%; RR 0.83, 95% CI 0.33 to 2.11; 181 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 duct occlusion after pancreaticoduodenectomyWe included two studies involving 351 participants: 188 were randomized 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 (17.0 days versus 16.5 days; MD 0.58 days, 95% CI -5.74 to 6.89; 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: 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。一些外科医生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2016年发表的一篇Cochrane系统评价的更新。
评估纤维蛋白封闭剂在预防胰腺手术后胰瘘方面的安全性、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（2018年第4期）、MEDLINE（1946年至2018年4月12日）、Embase（1980年至2018年4月12日）、科学引文索引扩展版（1900年至2018年4月12日）以及中国生物医学文献数据库（CBM）（1978年至2018年4月12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）的胰腺手术患者的随机对照试验。
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。对于二分结局，我们计算风险比（RR）（对于非常罕见的结局计算Peto比值比（OR）），对于连续结局计算均差（MD），并给出95%置信区间（CI）。
我们纳入了11项研究，共1462名参与者。
在远端胰腺切除术后应用纤维蛋白封闭剂加强胰腺残端闭合
我们纳入了7项研究，共860名参与者：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对术后胰瘘影响很小或无影响（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）。纤维蛋白封闭剂对术后死亡率可能也影响很小或无影响（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），或对总体术后发病率影响很小或无影响（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）。两组之间住院时间可能几乎没有差异（12.1天对11.4天；MD 0.32天，95%CI -1.06至1.70；755名参与者；4项研究；中等质量证据）。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应用纤维蛋白封闭剂加强胰肠吻合
我们纳入了3项研究，共251名参与者：胰十二指肠切除术后，115名被随机分配至纤维蛋白封闭剂组，136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（1.6%对6.2%；RR 0.25，95%CI 0.01至5.06；57名参与者；1项研究；极低质量证据）。纤维蛋白封闭剂对术后死亡率可能影响很小或无影响（0.1%对0.7%；Peto OR 0.15，95%CI 0.00至7.76；251名参与者；3项研究；低质量证据）或住院时间（12.8天对14.8天；MD -1.58天，95%CI -3.96至0.81；181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（33.7%对34.7%；RR 0.97，95%CI 0.65至1.45；181名参与者；2项研究；极低质量证据），或再次手术率（7.6%对9.2%；RR 0.83，95%CI 0.33至2.11；181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应用纤维蛋白封闭剂封闭胰管
我们纳入了2项研究，共351名参与者：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。纤维蛋白封闭剂对术后死亡率可能影响很小或无影响（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（17.0天对16.5天；MD 0.58天，95%CI -5.74至6.89；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）。一项研究报告了严重不良事件：在胰管封闭应用纤维蛋白封闭剂时，更多参与者在三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，纤维蛋白封闭剂对远端胰腺切除术患者的术后胰瘘可能影响很小或无影响。在接受胰十二指肠切除术的患者中，纤维蛋白封闭剂对预防术后胰瘘的效果尚不确定。
