REVIEW ARTICLE

Strategies to Reduce Pancreatic Stump Complications After Open or Laparoscopic Distal Pancreatectomy Colin Wilson, FRCS, Stuart Robinson, MRCS, Jeremy French, FRCS, and Steve White, FRCS

Abstract: Fibrin sealants could potentially protect against the occurrence of pancreatic fistula after distal pancreatectomy (DP). Fourteen relevant clinical studies (11 open and 3 laparoscopic DP) were identified using an extensive customized literature search, including 4 randomized controlled trials. Data from the 1 prospective randomized controlled trial with reasonable patient numbers found that fibrin reinforcement of the pancreatic stump suture line in open DP was associated with a significant reduction in fistula rate compared with suturing alone. Three other studies failed to show a significant difference in fistula rate. Two small scale nonrandomized retrospective studies each reported a reduced fistula rate associated with use of fibrin sealant in laparoscopic DP. On the basis of the current studies to evaluate the use of fibrin sealants in open and laparoscopic DP, application of fibrin glue to the pancreatic stump could help to reduce the incidence of troublesome pancreatic fistulas associated with this procedure. Key Words: distal pancreatectomy, sealant, fibrin glue, laparoscopic surgery, fistula

(Surg Laparosc Endosc Percutan Tech 2014;24:109–117)

I

n recent years improvements in patient selection and surgical techniques have reduced the mortality associated with pancreatic surgery, yet postsurgical complications are still common. In particular, pancreatic fistula is one of the most common complications after distal pancreatectomy (DP), and is generally hard to treat.1 The reported incidence of pancreatic fistulas after DP in papers published during 2011 and 2012 ranges from 14% to as high as 51%, and is clearly still an important cause of morbidity (Table 1).2–10 Laparoscopic distal pancreatectomy (LDP) is becoming increasingly recognized as a viable alternative to the open procedure with certain potential advantages such as reduced blood loss, shorter time to oral intake, reduced postoperative hospital stay, and lower analgesic requirements and also avoids the need for a large painful abdominal wound.11 However, one potential drawback of this approach is that it can be more difficult to effectively manage the pancreatic stump to avoid the development of pancreatic leaks from the cut surface.12 The reported incidence of pancreatic fistula after LDP is between 9% and 27%,3,7,13–18 which is comparable with most of the recently reported rates after open distal pancreatectomy (ODP).2–10 Received for publication April 29, 2013; accepted June 8, 2013. From the Department of Surgery, The Freeman Hospital, Newcastleupon-Tyne, UK. S.W. has received honoraria and travel grants from Baxter, Johnson and Johnson, and Nycomed. J.F. has received travel grants from Johnson and Johnson and Nycomed. The remaining authors declare no conflicts of interest. Reprints: Steve White, FRCS, Department of Surgery, The Freeman Hospital, Freeman Road, High Heaton, Newcastle-upon-Tyne, NE7 7DN, UK (e-mail: [email protected]). Copyright r 2014 by Lippincott Williams & Wilkins

Surg Laparosc Endosc Percutan Tech



Indeed, a recent meta-analysis of 10 comparative trials indicates that LDP is possibly associated with a lower rate of pancreatic leaks than the open procedure with odds ratios of 0.088 and 0.095, respectively.11 Absorbable, noninflammatory materials that could be applied to the duct or pancreatic stump or to reinforce suture or staples lines and thus protect against the occurrence of pancreatic fluid leakage and minor bleeding would be considered valuable to the pancreatic surgeon, particularly during laparoscopic procedures. Fibrin sealants are composed of fibrinogen and a source of thrombin, which combine to form a cross-linked insoluble fibrin matrix with both hemostatic and adhesive properties.19–23 They have been used in a wide range of surgical specialties for both hemostasis and to prevent fluid leakage, and have also been reported to reduce adhesion formation24 and enhance wound healing.25 The development of specialized equipment and applicators for the use of certain fibrin sealants during laparoscopic surgical procedures means that these agents can now be used in both open and laparoscopic surgery.23 The use of fibrin sealants has been explored both as agents to occlude the pancreatic duct and as an adjunct to mechanical closure of the pancreatic stump during DP. This article reviews the current experience in both ODP and LDP surgery with fibrin-based sealants.

SEARCH METHODOLOGY An extensive customized literature search was conducted to identify all relevant studies relating to the use of fibrin-based sealants during ODP or LDP (also known as distal, tail, or left resections) using the electronic PubMed, and Medline databases plus additional reference catalogs such as Google Scholar and the Cochrane Central Register of Controlled Trials 2011. Search terms used included the following general terms for these agents: sealant, fibrin glue, and the wild-card terms haemost* and hemost*, as well as the commercial names of individual products. In each case, the search term was combined with each of the following terms or wild-card terms to identify articles associated with this particular type of surgery: pancreatectom*, pancrea* resection, pancrea* fistula, and pancrea* leak. Relevant publications were then identified from these searches through manual examination of the titles or abstracts. Additional publications were also identified through manual searching of the cited references of key publications identified during the literature search. Manufacturer’s recommendations were also consulted through commercial product Web sites for each of the main products. Information based on the surgical experience of the author(s) with these products and surgical techniques is also included. Only studies involving the use of fibrin sealants in DPs, defined as pancreatic resection reaching the left side of the superior mesenteric vein, have been considered.

Volume 24, Number 2, April 2014

www.surgical-laparoscopy.com |

109

Surg Laparosc Endosc Percutan Tech

Wilson et al

TABLE 1. Current Published Rates of Pancreatic Fistula Formation After Distal Pancreatectomy

References Subhedar et al2 Mehta et al3

Country

n

Rate of Pancreatic Fistula (%)

USA France

149 30 (open) 30 (LPD) 283 64 16 14

14 17 (open) 13 (LPD) 24 24 25 28

Germany Reeh et al4 USA Sepesi et al5 Japan Okano et al6 UK Ammori and Ayiomamitis7 8 Europe Diener et al Frozanpor et al9 Soga et al10

Germany Japan

177 (stapler) 175 (hand sewn) 29 (no stent) 29 (with stent) 63

32 (stapler) 28 (hand sewn) 22 (no stent) 42 (with stent) 51

Data taken from surgical studies published during 2011 and 2012. LDP indicates laparoscopic distal pancreatectomy.

FIBRIN-BASED SEALANTS Fibrin sealants have been shown to be effective in the control of perioperative bleeding, for example, to control blood loss from cut surfaces that are difficult to suture, to provide additional support for sutures, for sealing cut tissue surfaces, and as adjuncts in wound healing.19–23 These agents are now routinely used to limit autologous blood loss across a wide range of surgical specialties including cardiovascular, orthopedic, thoracic, hepatic, pulmonary, and orthodontic surgery. A Cochrane meta-analysis of their use across surgical specialties in 18 separate trials suggested a significant 37% (relative risk, 0.63; 95% confidence interval, 0.45-0.88) reduction in allogenic blood transfusion associated with their use.26 In addition, these agents have been reported to have sealant properties27 and may also promote tissue healing.25 A number of commercially produced fibrin sealants are widely available (Table 2). Typically these consist of 2 separate major components: fibrinogen (human) and thrombin (human or bovine), which when mixed forms a cross-linked insoluble fibrin matrix or clot at the site of application. These products do not require active bleeding or blood-derived fibrinogen to achieve polymerization. The properties of the resulting fibrin clot are determined by the exact composition of the sealant: its mechanical strength being mainly dependent on the concentration of fibrinogen, whereas the rapidity of clot formation and the tensile strength of the final clot are determined by the relative thrombin concentration.28 Evidence also suggests that the clot formed by commercial fibrin sealants may be a less favorable bacterial culture medium than a physiological clot with, for example, 10 to 100 times slower growth of Staphylococcus aureus and Pseudomonas aeruginosa.29 Within the United Kingdom and the United States, commercial liquid fibrin sealants composed of fibrinogen derived from pooled donor human plasma plus human thrombin are available from 2 different manufacturers (Table 2). Some of these products also contain an antifibrinolytic agent to stabilize the clot and prevent enzymatic degradation. Tisseel (Baxter International, Deerfield, IL) contains the antifibrinolytic (and protease inhibitor) aprotinin, whereas Quixil, known as Crosseal in the United States, (Ethicon, Somerville, NJ) contains tranexamic acid. Evicel

110 | www.surgical-laparoscopy.com



Volume 24, Number 2, April 2014

(Ethicon) is a recently introduced product update of Quixil in which the need for an antifibrinolytic has been eliminated by chromatographic filtering techniques to reduce the plasminogen concentration. The inclusion of an antifibrinolytic and its exact mechanism of action are of particular relevance in pancreatic surgery where the resulting clot will be particularly prone to digestion by the many different exocrine enzymes produced and released by the pancreas. Most of these pancreatic exocrine enzymes are serine proteases, which are initially produced as inactive precursors and require the action of a protease for activation. Trypsin is the pivotal enzyme for the activation of most pancreatic zymogens, including chymotrypsinogen, proelastase, procarboxypeptidases A and B, prophospholipase A2, and kallikreininogen but not amylase. Trypsin is itself initially produced as the inactive precursor trypsinogen and requires the action of enterokinase for activation. Aprotinin is a serine protease inhibitor that inhibits trypsin, chymotrypsin, kallikrein, and plasmin, whereas tranexamic acid is a lysine derivative that exerts its antifibrinolytic action through the inhibition of plasminogen and preventing binding of plasmin to fibrin.30 Hence, an aprotinin-containing fibrin sealant such as Tisseel would be less susceptible to trypsin degradation and be the most suitable for use in pancreatic surgery. There are also a number of fibrin sealant systems in which the patient’s own plasma is used as a source of fibrinogen. Vitagel (Orthovita, Malvern, PA) uses the patient’s own plasma as a source of fibrinogen to be combined with commercial bovine collagen and thrombin. Some of these systems (eg, Vitagel, Vivostat; Vivostat A/S, Alleroed, Denmark) use straightforward plasma, whereas others (eg, Cryoseal; Thermogenesis, Rancho Cordova, CA) use devices to concentrate the fibrinogen from the plasma. The fibrinogen content of these autologous products is quite variable and usually lower than that of the commercially prepared agents. TachoComb H and TachoSil (Nycomed, Zurich, Switzerland) consist of a collagen sponge containing human fibrinogen and human thrombin with or without bovine aprotinin (Table 2). An earlier version of TachoComb used thrombin of bovine origin. In the past, there have been some safety concerns regarding the use of fibrin sealants. In particular, the inclusion of pooled donor plasma-derived components raises the possibility of viral or Creutzfeldt-Jacob disease transmission. However, for the agents in current use the manufacturing process includes various procedures designed to reduce this risk. These include donor screening, serological and PCR testing of donor blood, inventory hold periods, and various purification and viral inactivation processes including solvent/detergent cleansing and nanofiltration.31 The residual risk of pathogen transmission per vial for commercial fibrin sealants has recently been estimated as 100 mL.2,48–50 Management of the remaining pancreatic stump of the remnant pancreas after DP presents many difficulties and the best method of closure is unproven.8,47,48 The main factor contributing to leakage and fistula formation after DP is probably ischemia, a durable closure method of the pancreatic duct and the potential for abundant pancreatic leakage. In particular, a soft pancreas with nonfibrotic parenchyma is associated with a high incidence of postoperative pancreatic fistula because these often have well-preserved exocrine function.48 Various techniques have been proposed for the management of the pancreatic stump to reduce the potential for leak and fistula formation. Initially substances such as histoacryl or neoprene were used to occlude the pancreatic duct; however, there were concerns that they are nonabsorbable.51,52 Subsequently, the absorbable agent prolamine was tried; however, this often resulted in a marked inflammatory response with potential loss of pancreatic endocrine function.53–55 Although all these agents were effective in causing duct occlusion they are no longer used in this clinical setting because of these concerns. Various surgical techniques and devices for treating the cut surface of the pancreas to prevent pancreatic fistula after DP have been advocated. These include sutures or staples for closure, fibrin glue sealing, ultrasonic dissectors,

112 | www.surgical-laparoscopy.com

or an ultrasonically activated scalpel (UAS).47 The use of fibrin glue is considered in detail in subsequent sections of this article. Numerous studies have compared the rates of fistula formation after stapler versus suture closure of the pancreatic stump in DP but results have been conflicting. In the recently published DISPACT multicenter trial in which 450 patients were randomly assigned to either staple or suture closure of the pancreatic stump after DP, the rate of fistula formation was almost identical between the 2 groups (28% and 32%, respectively).8 Before the DISPACT trial, a meta-analysis of 16 studies found that there was no significant difference between the 2 groups with respect to fistula formation but that there was a trend favoring stapler closure (22.1% vs. 31.2%).56 A recent retrospective study of 64 patients undergoing DP performed by the same surgeon suggests that the size of stapler used may be a key factor affecting the risk of fistula formation.5 Division of the pancreatic parenchyma with vascular cartridges (red) resulted in a significantly lower fistula rate compared with green cartridges (P = 0.03; odds ratio, 9.0). In the authors’ own experience, standard 2.5 mm staples are not of sufficient length to go through the pancreatic parenchyma and can cause bleeding from the transection edge and increase the risk of a postoperative pancreatic fistula.12,46 For nondiseased pancreatic parenchyma, 3.5 mm staples may be sufficient; however, when the gland is thickened and fibrous, as is often the case in the setting of chronic pancreatitis, the additional security of 4.8 mm staples may be required. Most surgeons use stapling devices during laparoscopic DP primarily because of the restricted working space and time saved when compared with suturing; although there is some evidence to suggest a suture closure of the main duct may be efficacious.57 Using an ultrasonic dissector allows even small pancreatic ducts and vessels to be adequately sealed. In a randomized trial involving 58 patients undergoing DP with a nonfibrous pancreas, use of the ultrasonic dissector at the lowest vibration setting without suture closure of the pancreatic stump significantly reduced the incidence of pancreatic fistula compared with conventional division and suture.58 The UAS has a high ability to seal vessels by highfrequency ultrasonic vibration. In a small retrospective study involving 30 patients, the use of the UAS in DP was found to reduce the incidence of pancreatic fistula to 0% r

2014 Lippincott Williams & Wilkins

Surg Laparosc Endosc Percutan Tech



Volume 24, Number 2, April 2014

compared with 30% for conventional division of the pancreas.59 Furthermore, no bleeding was observed on the cut surface in the UAS group, and so no clamping or parenchymal suturing was needed for hemostasis. The efficacy of these methods is likely to be dependent on the state of the pancreas, such as the grade of fibrotic change and thickness.58 Adjustment of the vibration setting according to the state of the pancreas may also be of critical importance, particularly with the ultrasonic dissector.60 More recently, a variety of special surgical techniques designed to reduce the risk of fistula formation have been proposed. These include the use of a seromuscular patch of jejunum applied to the pancreatic transection line,61 transampullary pancreatic duct stenting,62–64 duct-to-mucosa pancreaticogastrostomy,65 or covering the stump with a falciform ligament pedicle flap.66 At present, these techniques have only been evaluated in single and usually small anecdotal studies, and further work is needed to fully determine their effectiveness. A recently published small randomized controlled trial (RCT) comparing intraoperative stenting with standard techniques, actually found a higher rate of pancreatic fistula in the group that were stented (42% vs. 22%) although this was not statistically significant (P = 0.22).9 Somatostatin analogs such as octreotide, lanreotide, or vapreotide can decrease splanchnic blood flow and

Distal Pancreatic Stump Sealants

pancreatic fluid secretion, and thus have the potential to reduce fluid leakage and fistula formation.67,68 A retrospective study of 64 patients undergoing DP has reported that postoperative prophylactic octreotide therapy is associated with a lower risk of pancreatic fistula.49 A recent Cochrane meta-analysis of studies investigating the use of prophylactic somatostatin analogs in all pancreatic resections identified 17 RCTs.69,70 Although the incidence of pancreatic fistula overall was lower in the somatostatin group (relative risk, 0.64; 95% confidence interval, 0.530.78), analysis of trials that clearly distinguished clinically significant fistulas revealed no difference between the 2 groups. Most of the patients in these trials (68%) were actually undergoing pancreatoduodenectomy rather than DP, and unfortunately the authors were unable to perform a planned subanalysis for DP as the outcome data for this subgroup were not available from the published trials. Hence, the value of prophylactic somatostatin analogs in preventing fistula formation after DP is still unclear.

USE OF FIBRIN SEALANTS IN ODP A total of 11 studies describing the use of fibrin sealants as adjuncts in ODP were identified from the literature search, including 5 RCTs.10,12,71–80 Of these, detailed

TABLE 3. Current Experience With the Use of Fibrin Sealants as Adjuncts to Stump Closure in Open and Laparoscopic Distal Pancreatectomy

References Suzuki et al72

Type of Study Prospective randomized controlled trial Prospective randomized controlled trial

Bassi et al73 (Data taken from Fingerhut et al71) D’Andrea et al74 Prospective randomized controlled trial Ochiai et al75 Marczell76 Mita et al77 Ikegami et al78 Ohwada et al79 Suc et al80

Velanovich81 Robinson et al12 Pavlik Marangos et al82

Product Used Tisseel fibrin sealant Unspecified fibrin sealant

Unspecified fibrin sealant

Nonrandomized retrospective study Case series study Case series study Case series study Nonrandomized prospective study Prospective randomized controlled trial

PGA felt plus fibrinogencoated/thrombin-coated collagen patch Tisseel fibrin sealant TachoComb PGA felt plus fibrin sealant Unspecified fibrin sealant: spray vs. sandwich technique

Nonrandomized retrospective study Nonrandomized retrospective study Nonrandomized retrospective study

Tisseel fibrin sealant

Tisseel fibrin sealant to occlude pancreatic duct

Tisseel fibrin sealant TachoSil

Surgical Procedure

Findings

Open DP Fibrin group: n = 26 Suture group: n = 30 Open DP Fibrin group: n = 11 Suture group: n = 15

Significantly lower fistula rate (15.4% vs. 40.0%; P = 0.04)

Range of open pancreatic surgery cases including 23 DP Fibrin DP group: n = 10 Control DP group: n = 13 Open DP Fibrin group: n = 26 Control group: n = 37 Open DP: n = 85 Open DP: n = 25 Open DP: n = 9 Open DP: n = 111

Fistula rates of 0/10 in fibrin group vs. 1/13 control; nonsignificant

Open DP Fibrin occlusion group: n = 22 Control group: n = 19 Laparoscopic DP Fibrin group: n = 8 Control group: n = 13 Laparoscopic DP Fibrin group: n = 6 Control group: n = 8 Laparoscopic DP Fibrin group: n = 73 Control group: n = 48

Fistula rates of 27% vs. 33%; nonsignificant

Significantly lower fistula rate (4% vs. 27%; P = 0.017) Fistula rate of 2/85 Fistula rate of 20% Fistula rate of 1/9 Significantly lower fistula rates in sandwich group (9.0%) vs. spray group (26.8%) No difference in fistula rates: fibrin group (18%) vs. control (16%) Fistula rate of 0/8 in fibrin group vs. 3/11 in control group Fistula rate of 0/6 in fibrin group vs. 1/8 in control group No difference in fistula rates: fibrin group (12%) vs. control (8%)

DP indicates distal pancreatectomy; PGA, polyethylene glycolic acid.

r

2014 Lippincott Williams & Wilkins

www.surgical-laparoscopy.com |

113

Wilson et al

Surg Laparosc Endosc Percutan Tech

information could only be found in 4 studies,71,72,74,80 and 1 was excluded on the basis of insufficient citation data. These studies investigated either the use of fibrin sealants as agents to cause obstruction of the pancreatic duct or as adjuncts to mechanical closure of the pancreatic stump (Table 3). The studies also differ in the type of sealant used and also the exact method of application. One recent critical appraisal of the literature relating to the use of sealants in pancreatic surgery was published in 2009 but this did not distinguish between studies involving DP and other types of pancreatic resection.71

FIBRIN SEALANTS AS ADJUNCTS IN STUMP CLOSURE One prospective RCT conducted by Suzuki et al72 evaluated the use of fibrin sealants on the pancreatic stump after DP for the prevention of postoperative pancreatic fistula. Twenty-six of 56 patients were randomly assigned to have the fibrin sealant Tisseel applied to the suture line of the pancreatic stump with the main duct ligated, whereas the remainder had closure with suturing alone. Postoperative pancreatic fistulas occurred in only 4 patients (15.4%) in the fibrin glue group compared with 12 (40.0%) in the control group (P = 0.04). These results contradict the findings of another but smaller prospective randomized study by Bassi and colleagues who compared 5 different techniques for the closure of the pancreatic stump in 69 patients undergoing DP.71,73 Consecutive patients were randomized to 1 of 5 treatment groups: stump closure with simple suture closure plus main duct ligation (n = 15); suture closure plus ligation reinforced with fibrin sealant (n = 11); suture closure plus ligation reinforced with polypropylene mesh (n = 15); pancreaticojejunostomy (n = 14); or suture closure with a stapler (n = 14). No statistically significant difference in fistula rate was found between any of the 5 groups despite a wide range of fistula rates ranging from 7% in the pancreaticojejunostomy group to 33% in the simple closure plus ligation group. Rates in the group receiving fibrin sealant were 27%. Another RCT including 97 patients by D’Andrea et al74 has also investigated the potential benefits of using fibrin sealants in pancreatic surgery. Looking at combined data for all pancreatic surgery cases including 23 DPs (or left pancreatic resections) and 74 cases involving surgery on the head of the pancreas (eg, Whipples type procedures) or tumor excision there was no overall benefit. Considering just those patients undergoing DP, no patient in which the pancreatic stump was treated with a fibrin sealant developed a complication (0/10), whereas in the control group 1 patient developed a pancreatic fistula (1/13). A further nonrandomized retrospective study has investigated the effect of using fibrin sealants to prevent fistula formation in DP. The study conducted by Ochiai et al75 actually looked at the effect of adopting a new technique involving the use of polyethylene glycolic acid felt wrapped around the predicted division site plus laying a fibrinogencoated/thrombin-coated collagen patch onto the transected stump in 63 patients undergoing DP. After introduction of this procedure, the incidence of fistula formation dropped from 27% to 4% (P = 0.017). In a separate publication, the authors have also identified risk factors for postoperative pancreatic fistula and concluded that the use of this technique and blood loss during the operation were the most significant factors for the development of severe fistula.10

114 | www.surgical-laparoscopy.com



Volume 24, Number 2, April 2014

There have also been noncomparative or anecdotal reports from single centers reporting the use of fibrin sealants to reinforce the resection surfaces in DP with low fistula rates. For example, Marczell76 reports that only 2 of 85 DPs developed pancreatic fistulas with their technique of covering the transection surface with an additional coat of the fibrin sealant Tisseel. Mita et al77 also report a technique to prevent pancreatic fistulas in DP which involves application of the fibrin adhesive TachoComb to the staple line of the pancreas before stapling. Their overall incidence of pancreatic fistula was 20%. Ikegami et al78 describe a technique using the application of polyethylene glycolic acid felt plus fibrin glue to the cut surface of the pancreas and report a fistula rate of only 1 of 9 patients. Ohwada et al79 have suggested that using a “fibrin glue sandwich” technique (involving spraying the sealant so as to cover and join the cut surface of the pancreatic remnant which is then held closed with sutures) may be more effective at preventing fistula than just spraying alone. In their nonrandomized study involving 111 patients undergoing DP, pancreatic fistulas occurred in only 9.0% of the sandwich group versus 26.8% of the sealant group.

OBSTRUCTION OF THE PANCREATIC DUCT WITH A FIBRIN SEALANT Only 1 RCT has investigated the effect of occluding the main pancreatic duct with a fibrin sealant after DP. Suc et al80 investigated whether temporary occlusion of the main pancreatic duct with fibrin glue can decrease the incidence of intra-abdominal complications after pancreatoduodenectomy or DP. In their randomized study involving 182 consecutive patients there was no difference in the incidence of Z1 intra-abdominal complications, or pancreatic fistula, between the 102 patients who underwent pancreatic resection followed by ductal occlusion with Tisseel (made slowly resorbable by the addition of aprotinin) and the 80 who underwent resection without ductal occlusion. In the DP subgroup, 4 of the 22 (18%) of the ductal occlusion group developed complications versus 3 of 19 (16%) in the control group; on the basis of 1 novel trial with equivalent results it is difficult to conclude that ductal occlusion offers anything over transaction or anastomotic line reinforcement.

LDP The technical complexity of pancreatic surgery and difficulties in obtaining an adequate and appropriate operative field for this retroperitoneal organ has meant that the development of minimally invasive techniques for pancreatic resections has been relatively slow compared with many other procedures in many other surgical specialties. However, with recent advances in laparoscopic TABLE 4. Complication Rates in Laparoscopic Versus Open Distal Pancreatectomies

Complication

Odds Ratio

95% Confidence Interval

0.49 0.57 0.32 0.68

0.27-0.89 0.34-0.96 0.19-0.53 0.47-0.98

Overall Major complication Surgical site infection Pancreatic fistula

Data shown are taken from the meta-analysis of 10 studies conducted by Nigri et al.11

r

2014 Lippincott Williams & Wilkins

Surg Laparosc Endosc Percutan Tech



Volume 24, Number 2, April 2014

Distal Pancreatic Stump Sealants

FIGURE 2. Laparoscopic application of Tisseel to the pancreatic stump. A, The Duplocath 315 MIS applicator and the clips on the splenic artery are apparent, with the postapplication appearance of the pancreatic stump in (B). Taken from Robinson et al.12

techniques and instruments, LDP is becoming increasingly recognized as a viable treatment option for tumors in the distal part of the pancreas, probably because of the lack of a pancreatic ductal anastomosis.83,84 Many institutions around the world are now reporting the use of LDP surgery and have concluded that it is a safe and feasible option in experienced centers.3,13,85–88 A recent meta-analysis of trials comparing minimally invasive and open procedures for DP identified 10 studies with 349 patients undergoing LDP and 380 patients undergoing an open procedure.11 Their analysis found that patients undergoing LDP had less blood loss, a shorter time to oral intake, and a shorter postoperative stay. Furthermore, the laparoscopic approach was also associated with fewer overall complications, surgical site infections, and pancreatic fistulas (Table 4).

CONCLUSIONS Although there remains a lack of high-quality evidence to support the use of fibrin sealants in DP surgery, many centers have taken this technology on to support closure of the pancreatic duct. The largest RCT72 currently reported does suggest a reduced pancreatic fistula rate, but this needs to be confirmed in further multicenter trials. To date there have been no significant harms reported with these products in pancreatic surgery and it may be that a combination of laparoscopic surgery and staple closure with a fibrin sealant covering will emerge as the “gold standard”: combining the benefits of minimal access surgery without compromising the length of operating time and related postoperative outcomes. ACKNOWLEDGMENT

USE OF FIBRIN SEALANTS IN LDP The systematic literature search identified only 2 comparative studies describing the use of fibrin sealants as adjuncts in LDP. Both of these studies were nonrandomized retrospective studies and were also small in scale. The first of these involved a total of 21 patients, and application of fibrin sealant (Tisseel) to the transection of the pancreatic stump in 8 patients was associated with fewer fistulas (0% vs. 23%).81 In the second study involving 14 patients undergoing LDP with staple closure of the pancreatic resection, there were no cases of fistula in the 6 patients in which the fibrin sealant Tisseel was applied to the pancreatic stump (Fig. 2), and 1 case of fistula where fibrin sealant was not used.12 Other authors have also reported that they are currently using the fibrin sealant Tisseel using the Duplocath system in their DPs but that it is too early to say whether this has resulted in a decrease in fistula formation.89 In their published description of laparoscopic pancreatic resection techniques, Cuschieri et al88 note that the application of fibrin sealants to the residual pancreatic stump may reduce pancreatic fistula. Røsok et al87 have reported that since 2005 they have been using a fibrinogen-coated/thrombincoated collagen sponge (TachoSil) to seal the resection margin during laparoscopic pancreatic resections. However, a retrospective analysis of 121 patients undergoing LDPs at their institution since 1998 found that there was no significant difference in the rate of postoperative fistula between the group in which the pancreatic stump was covered with TachoSil [12% (9/73)] and the group where TachoSil was not used [8% (4/48)].82 r

2014 Lippincott Williams & Wilkins

The authors thank M.E. Appleyard who provided assistance with the preparation and editing of the manuscript through Contract Medical Communications Ltd (Teddington, UK) and this service was funded by Baxter Healthcare Limited. REFERENCES 1. Hackert T, Werner J, Bu¨chler MW. Postoperative pancreatic fistula. Surgeon. 2011;9:211–217. 2. Subhedar PD, Patel SH, Kneuertz PJ, et al. Risk factors for pancreatic fistula after stapled gland transection. Am Surg. 2011;77:965–970. 3. Mehta SS, Doumane G, Mura T, et al. Laparoscopic versus open distal pancreatectomy: a single-institution case-control study. Surg Endosc. 2012;26:402–407. 4. Reeh M, Nentwich MF, Bogoevski D, et al. High surgical morbidity following distal pancreatectomy: still an unsolved problem. World J Surg. 2011;35:1110–1117. 5. Sepesi B, Moalem J, Galka E, et al. The influence of staple size on fistula formation following distal pancreatectomy. J Gastrointest Surg. 2012;16:267–274. 6. Okano K, Kakinoki K, Suto H, et al. Persisting ratio of total amylase output in drain fluid can predict postoperative clinical pancreatic fistula. J Hepatobiliary Pancreat Sci. 2011;18: 815–820. 7. Ammori BJ, Ayiomamitis GD. Laparoscopic pancreaticoduodenectomy and distal pancreatectomy: a UK experience and a systematic review of the literature. Surg Endosc. 2011;25: 2084–2099. 8. Diener MK, Seiler CM, Rossion I, et al. Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial. Lancet. 2011;377:1514–1522.

www.surgical-laparoscopy.com |

115

Wilson et al

Surg Laparosc Endosc Percutan Tech

9. Frozanpor F, Lundell L, Segersva¨rd R, et al. The effect of prophylactic transpapillary pancreatic stent insertion on clinically significant leak rate following distal pancreatectomy: results of a prospective controlled clinical trial. Ann Surg. 2012; 255:1032–1036. 10. Soga K, Ochiai T, Sonoyama T, et al. Risk factors for postoperative pancreatic fistula in distal pancreatectomy. Hepatogastroenterology. 2011;58:1372–1376. 11. Nigri GR, Rosman AS, Petrucciani N, et al. Metaanalysis of trials comparing minimally invasive and open distal pancreatectomies. Surg Endosc. 2011;25:1642–1651. 12. Robinson S, Saif R, Charnley RM, et al. Surgical adjuncts to laparoscopic distal pancreatectomy. Minim Invasive Ther Allied Technol. 2011;20:369–373. 13. Kooby DA, Gillespie T, Bentrem D, et al. Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches. Ann Surg. 2008;248:438–446. 14. Sa Cunha A, Rault A, Beau C, et al. A single-institution prospective study of laparoscopic pancreatic resection. Arch Surg. 2008;143:289–295. 15. Pryor A, Means JR, Pappas TN. Laparoscopic distal pancreatectomy with splenic preservation. Surg Endosc. 2007; 21:2326–2330. 16. Pierce RA, Spitler JA, Hawkins WG, et al. Outcome analysis of laparoscopic resection of pancreatic neoplasms. Surg Endosc. 2007;21:579–586. 17. Mabrut J, Fernandez-Cruz L, Azagra JS, et al. Laparoscopic pancreatic resection: results of a multicenter European study of 127 patients. Surgery. 2005;137:597–605. 18. Kim SC, Park KT, Hwang JW, et al. Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution. Surg Endosc. 2008;22:2261–2268. 19. Seyednejad H, Imani M, Jamieson T, et al. Topical haemostatic agents. Br J Surg. 2008;95:1197–1225. 20. Spotnitz WD, Burks S. Hemostats, sealants, and adhesives: components of the surgical toolbox. Transfusion. 2008;48: 1502–1516. 21. Wheat JC, Wolf JS. Advances in bioadhesives, tissue sealants, and hemostatic agents. Urol Clin N Am. 2009;36:265–275. 22. Achneck HE, Sileshi B, Jamiolkowski RM, et al. A comprehensive review of topical hemostatic agents. Efficacy and recommendations for use. Ann Surg. 2010;251:217–228. 23. Saif R, Jacob M, Robinson S, et al. Use of fibrin-based sealants and gelatin-matrix hemostats in laparoscopic liver surgery. Surg Laparosc Endosc Percutan Tech. 2011;21: 131–141. 24. Prieto-Dı´ az-Cha´vez E, Medina-Cha´vez JL, Ramı´ rez-Barba EJ, et al. Reduction of peritoneal adhesion to polypropylene mesh with the application of fibrin glue. Acta Chir Belg. 2008;108: 433–437. 25. Inalo¨z SS, Ak HE, Vayla V, et al. Comparison of microsuturing to the use of tissue adhesives in anastomosing sciatic nerve cuts in rats. Neurosurg Rev. 1997;20:250–258. 26. Carless PA, Henry DA, Anthony DM. Fibrin sealant use for minimising peri-operative allogeneic blood transfusion. Coch Database Syst Rev. 2003;(1):CD004171. 27. Uetsuji S, Komada Y, Kwon AH, et al. Prevention of pleural effusion after hepatectomy using fibrin sealant. Int Surg. 1994; 79:135–137. 28. Yoshida H, Hirozane K, Kamiya A. Adhesive strength of autologous fibrin glue. Biol Pharm Bull. 2000;23:313–317. 29. Stanek G, Bo¨sch P, Weber P. Comparison of growth of Staphylococcus aureus in a fibrin-clotting system and in clotted blood—a quantitative investigation (author’s translation). Zentralbl Bakteriol [Orig A]. 1978;240:441–446. 30. Slaughter TF, Greenberg CS. Antifibrinolytic drugs and perioperative hemostasis. Am J Hematol. 1997;56:32–36. 31. Busittil RW. A comparison of antifibrinolytic agents used in hemostatic fibrin sealants. J Am Coll Surg. 2003;197: 1021–1028.

116 | www.surgical-laparoscopy.com



Volume 24, Number 2, April 2014

32. Horowitz B, Busch M. Estimating the pathogen safety of manufactured human plasma products: application to fibrin sealants and to thrombin. Transfusion. 2008;48:1739–1753. 33. Hino M, Ishiko O, Honda KI, et al. Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery. Br J Haematol. 2000;108:194–195. 34. Kawamura M, Sawafuji M, Watanabe M, et al. Frequency of transmission of human parvovirus B19 infection by fibrin sealant used during thoracic surgery. Ann Thorac Surg. 2002; 73:1098–1100. 35. Ba¨nninger H, Hardegger T, Tobler A, et al. Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V. Br J Haematol. 1993;85:528–532. 36. Sarfat MR, DiLorenzo DJ, Kraiss LW, et al. Severe coagulopathy following intraoperative use of topical thrombin. Ann Vasc Surg. 2004;18:349–351. 37. Crow SS, Sullivan VV, Ayosola AE, et al. Postoperative coagulopathy in a pediatric patient after exposure to bovine thrombin. Ann Thorac Surg. 2007;83:1547–1549. 38. Kozak RW, Golker CF, Stadler P. Transmissible spongiform encephalopathies (TSE): minimizing the risk of transmission by biological/biopharmaceutical products: an industry perspective. Dev Biol Stand. 1996;88:257–264. 39. Go¨lker CF, Whiteman MD, Gugel KH, et al. Reduction of the infectivity of scrapie agent as a model for BSE in the manufacturing process of Trasylol. Biologicals. 1996;24: 103–111. 40. Waclawiczek HW, Boeckl O. Pancreatic duct occlusion with fibrin sealant for the protection of the pancreatic digestive anastomosis following resection of the pancreatic head (experimental and clinical study). In: Waclawiczek HW, ed. Progress in Fibrin Sealing. Berlin: Springer Verlag; 1989: 79–96. 41. Houvenaeghel G, Orsoni P, Monges G, et al. The value of histological study by surface analysis of preserved and injected pancreatic grafts: a prospective controlled study in dogs. Int Surg. 1993;78:36–39. 42. Hauser CJ. Hemostasis of solid viscus trauma by intraparenchymal injection of fibrin glue. Arch Surg. 1989;124:291–293. 43. Stojanovic M, Jeremic M, Stojanovic P, et al. Use of fibrin glue in the prevention of leakage in pancreatico-jejunal anastomoses. Acta Chir Iugosl. 2002;49:39–45. 44. Jon B, Cecka F, Subrt Z, et al. A novel approach for reinforcing the pancreatic remnant in laparoscopic distal pancreatectomy: an experimental study on a porcine model. Surg Laparosc Endosc Percutan Tech. 2010;20:e50–e53. 45. La¨msa¨ T, Jin HT, Sand J, et al. Tissue adhesives and the pancreas: biocompatibility and adhesive properties of 6 preparations. Pancreas. 2008;36:261–266. 46. Wilson CH, White SA. Single-centre experience of laparoscopic pancreatic surgery. Br J Surg. 2010;97:1891–1892. 47. Kuroki T, Tajima Y, Kanematsu T. Surgical management for the prevention of pancreatic fistula following distal pancreatectomy. J Hepatobiliary Pancreat Surg. 2005;12:283–285. 48. Kah Heng CA, Salleh I, San TS, et al. Pancreatic fistula after distal pancreatectomy: incidence, risk factors and management. ANZ J Surg. 2010;80:619–623. 49. Ridolfini MP, Alfieri S, Gourgiotis S, et al. Risk factors associated with pancreatic fistula after distal pancreatectomy, which technique of pancreatic stump closure is more beneficial. World J Gastroenterol. 2007;13:5096–5100. 50. Eguchi H, Nagano H, Tanemura M. A thick pancreas is a risk factor for pancreatic fistula after a distal pancreatectomy: selection of the closure technique according to the thickness. Dig Surg. 2011;28:50–56. 51. Tran K, Van Eijck C, Di Carlo V, et al. Occlusion of the pancreatic duct versus pancreaticojejunostomy: a prospective randomized trial. Ann Surg. 2002;236:422–428. 52. Little JM, Lauer C, Hogg J. Pancreatic duct obstruction with an acrylate glue: a method for producing pancreatic exocrine atrophy. Surgery. 1977;81:243–249. r

2014 Lippincott Williams & Wilkins

Surg Laparosc Endosc Percutan Tech



Volume 24, Number 2, April 2014

53. Gebhardt C, Stolte M. Occlusion of pancreatic duct system by injection of a fast-solidifying amino acid solution. Langenbecks Arch Chir. 1978;346:149–166. 54. Isaksson G, Lundquist I, Ihse I. Effects on the exocrine and endocrine pancreas of duct occlusion with two different tissue glues in the rat. Eur Surg Res. 1983;15:136–144. 55. Gabel H, Wedel N, Palmertz B, et al. Pancreatic duct occlusion with Ethibloc. An experimental study in juvenile pigs. Horm Metab Res Suppl. 1983;13:1–8. 56. Zhou W, Lv R, Wang X, et al. Stapler vs. suture closure of pancreatic remnant after distal pancreatectomy: a metaanalysis. Am J Surg. 2010;200:529–536. 57. Bilimoria MM, Cormier JN, Mun Y, et al. Pancreatic leak after left pancreatectomy is reduced following main pancreatic duct ligation. Br J Surg. 2003;90:190–196. 58. Suzuki Y, Fujino Y, Tanioka Y, et al. Randomised clinical trial of ultrasonic dissector or conventional division in distal pancreatectomy for non-fibrotic pancreas. Br J Surg. 1999;86:608–611. 59. Sugo H, Mikami Y, Matsumoto F, et al. Comparison of ultrasonically activated scalpel versus conventional division for the pancreas in distal pancreatectomy. J Hepatobiliary Pancreat Surg. 2001;8:349–352. 60. Kuroda Y, Tanioka Y, Suzuki Y, et al. Distal pancreatectomy using the ultrasonic dissector. J Am Coll Surg. 1995;180:737–738. 61. Ola´h A, Issekutz A, Bela´gyi T, et al. Randomized clinical trial of techniques for closure of the pancreatic remnant following distal pancreatectomy. Br J Surg. 2009;96:602–607. 62. Fischer CP, Bass B, Fahy B, et al. Transampullary pancreatic duct stenting decreases pancreatic fistula rate following left pancreatectomy. Hepatogastroenterology. 2008;55:244–248. 63. Oida T, Mimatsu K, Kanou H, et al. A new surgical technique of transduodenal pancreatic juice drainage prevents pancreatic fistula following distal pancreatectomy. Hepatogastroenterology. 2011;58:1398–1402. 64. Oida T, Mimatsu K, Kawasaki A, et al. Transduodenal pancreatic juice drainage for preventing pancreatic fistula formation after distal pancreatectomy. Hepatogastroenterology. 2011;58:177–182. 65. Sudo T, Murakami Y, Uemura K, et al. Distal pancreatectomy with duct-to-mucosa pancreaticogastrostomy: a novel technique for preventing postoperative pancreatic fistula. Am J Surg. 2011;202:77–81. 66. Walters DM, Stokes JB, Adams RB, et al. Use of a falciform ligament pedicle flap to decrease pancreatic fistula after distal pancreatectomy. Pancreas. 2011;40:595–599. 67. Kohler E, Beglinger C, Dettwiler S, et al. Effect of a new somatostatin analogue on pancreatic function in healthy volunteers. Pancreas. 1986;1:154–159. 68. Lembcke B, Creutzfeldt W, Schleser S, et al. Effect of the somatostatin analogue sandostatin (SMS 201–995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men. Digestion. 1987;36:108–124. 69. Koti RS, Gurusamy KS, Fusai G, et al. Meta-analysis of randomized controlled trials on the effectiveness of somatostatin analogues for pancreatic surgery: a Cochrane review. HPB. 2010;12:155–165. 70. Gurusamy KS, Koti R, Fusai G, et al. Somatostatin analogues for pancreatic surgery. Coch Database Syst Rev. 2013;(4): CD008370.

r

2014 Lippincott Williams & Wilkins

Distal Pancreatic Stump Sealants

71. Fingerhut A, Veyrie N, Ata T, et al. Use of sealants in pancreatic surgery: critical appraisal of the literature. Dig Surg. 2009;26:7–14. 72. Suzuki Y, Kuroda Y, Morita A, et al. Fibrin glue sealing of pancreatic injuries, resections, and anastomoses. Arch Surg. 1995;130:952–955. 73. Bassi C, Butturini G, Falconi M, et al. Prospective randomised pilot study of management of the pancreatic stump following distal resection. HPB Surg. 1999;2:203–207. 74. D’Andrea AA, Costantino V, Speri C, et al. Human fibrin sealant in pancreatic surgery: is it useful in preventing fistulas? A prospective randomized study. Ital J Gastroenterol. 1994;26: 283–286. 75. Ochiai T, Sonoyama T, Soga K, et al. Application of polyethylene glycolic acid felt with fibrin sealant to prevent postoperative pancreatic fistula in pancreatic surgery. J Gastrointest Surg. 2010;14:884–890. 76. Marczell AP. Indications for fibrin sealing in pancreatic surgery with special regard to occlusion nonanastomosed stump with fibrin sealant. Surg Technol Int. 2000;8:32–36. 77. Mita K, Ito H, Fukumoto M, et al. A fibrin adhesive sealing method for the prevention of pancreatic fistula following distal pancreatectomy. Hepatogastroenterology. 2011;58:604–608. 78. Ikegami T, Maeda T, Kayashima H, et al. Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy. Surg Today. 2011;41:1224–1227. 79. Ohwada S, Ogawa T, Tanahashi Y, et al. Fibrin glue sandwich prevents pancreatic fistula following distal pancreatectomy. World J Surg. 1998;22:494–498. 80. Suc B, Msika S, Fingerhut A, et al. Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of intra-abdominal complications after pancreatic resection: prospective randomized trial. Ann Surg. 2003;237:57–65. 81. Velanovich V. The use of tissue sealant to prevent fistula formation after laparoscopic distal pancreatectomy. Surg Endosc. 2007;21:1222. 82. Pavlik Marangos I, Røsok BI, Kazaryan AM, et al. Effect of TachoSil patch in prevention of postoperative pancreatic fistula. J Gastrointest Surg. 2011;15:1625–1629. 83. Al-Taan OS, Stephenson JA, Briggs C, et al. Laparoscopic pancreatic surgery: a review of present results and future prospects. HPB. 2010;12:239–243. 84. Merchant NB, Parikh AA, Kooby DA. Should all distal pancreatectomies be performed laparoscopically? Adv Surg. 2009;43:283–300. 85. Tang CN, Tsui KK, Ha JP, et al. Laparoscopic distal pancreatectomy: a comparative study. Hepatogastroenterology. 2007;54:265–271. 86. Velanovich V. Case-control comparison of laparoscopic versus open distal pancreatectomy. J Gastrointest Surg. 2006;10:95–98. 87. Røsok BI, Marangos IP, Karayan AM, et al. Single-centre experience of laparoscopic pancreatic surgery. Br J Surg. 2010; 97:902–909. 88. Cuschieri A, Jakimowicz JJ. Laparoscopic pancreatic resections. Semin Laparosc Surg. 1998;5:168–179. 89. Røsok BI, Edwin B. Authors’ reply: single-centre experience of laparoscopic pancreatic surgery. Br J Surg. 2010; 97:1892.

www.surgical-laparoscopy.com |

117

Strategies to reduce pancreatic stump complications after open or laparoscopic distal pancreatectomy.

Fibrin sealants could potentially protect against the occurrence of pancreatic fistula after distal pancreatectomy (DP). Fourteen relevant clinical st...
230KB Sizes 0 Downloads 3 Views