Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. 2018

Junhua Gong, and Sirong He, and Yao Cheng, and Nansheng Cheng, and Jianping Gong, and Zhong Zeng
Organ Transplant Center, First Affiliated Hospital of Kunming Medical University, No. 295, Xi Chang Road, Kunming, Yunnan, China, 650032.

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. 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.

UI MeSH Term Description Entries
D007902 Length of Stay The period of confinement of a patient to a hospital or other health facility. Hospital Stay,Hospital Stays,Stay Length,Stay Lengths,Stay, Hospital,Stays, Hospital
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010180 Pancreatectomy Surgical removal of the pancreas. (Dorland, 28th ed) Pancreatectomies
D010185 Pancreatic Fistula Abnormal passage communicating with the PANCREAS. Fistula, Pancreatic,Fistulas, Pancreatic,Pancreatic Fistulas
D011183 Postoperative Complications Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. Complication, Postoperative,Complications, Postoperative,Postoperative Complication
D012086 Reoperation A repeat operation for the same condition in the same patient due to disease progression or recurrence, or as followup to failed previous surgery. Revision, Joint,Revision, Surgical,Surgery, Repeat,Surgical Revision,Repeat Surgery,Revision Surgery,Joint Revision,Revision Surgeries,Surgery, Revision
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014014 Tissue Adhesives Substances used to cause adherence of tissue to tissue or tissue to non-tissue surfaces, as for prostheses. Adhesive, Tissue,Adhesives, Tissue,Tissue Adhesive
D015718 Fibrin Tissue Adhesive An autologous or commercial tissue adhesive containing FIBRINOGEN and THROMBIN. The commercial product is a two component system from human plasma that contains more than fibrinogen and thrombin. The first component contains highly concentrated fibrinogen, FACTOR VIII, fibronectin, and traces of other plasma proteins. The second component contains thrombin, calcium chloride, and antifibrinolytic agents such as APROTININ. Mixing of the two components promotes BLOOD CLOTTING and the formation and cross-linking of fibrin. The tissue adhesive is used for tissue sealing, HEMOSTASIS, and WOUND HEALING. Autologous Fibrin Tissue Adhesive,Fibrin Adhesive,Fibrin Glue,Fibrin Sealant System,Fibrinogen Adhesive,Beriplast,Crosseal,Fibrin Klebe System Immuno,Fibrin Seal,Fibrin Sealant,Fibrin Sealant, Human,Tisseel,Tissel,Tissucol,Transglutine,Adhesive, Fibrin,Adhesive, Fibrin Tissue,Adhesive, Fibrinogen,Glue, Fibrin,Human Fibrin Sealant,Seal, Fibrin,Sealant System, Fibrin,Sealant, Fibrin,Sealant, Human Fibrin,Tissue Adhesive, Fibrin
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical

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