Abstract
Background
Fibrin sealants and topical glue have been studied to reduce the incidence of postoperative pancreatic fistulas (POPF) after pancreatico-enteric anastomosis, but a definitive innovation is still needed. We aim to evaluate the effectiveness of fibrin sealant patch applied to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF.
Methods
This study was a single-center, prospective, randomized, phase IV trial involving three pancreaticobiliary surgeons. The primary outcome was POPF; secondary outcomes included complications, drain removal days, hospital stay, readmission rate, and cost. Risk factors for POPF were identified by logistic regression analysis.
Results
A total of 124 patients were enrolled. Biochemical leakage (BL) or POPF occurred in 16 patients (25.8%) in the intervention group and 23 patients (37.1%) in the control group (no statistical significance). Clinically relevant POPF occurred in 4 patients (6.5%) in both the intervention and control groups (p = 1.000). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not statistically different between two groups. Complication rates were not different between the two groups (p = 0.506); nor were readmission rates (12.9% vs. 11.3%, p = 1.000) or cost ($13,549 vs. $15,038, p = 0.103). In multivariable analysis, age and soft pancreas texture were independent risk factors for BL or POPF in this study. Applying fibrin sealant patch is not a negative risk factor, but the p value may indicate a likelihood of reducing the incidence of BL (p = 0.084).
Conclusions
Fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF or other postoperative complications. This study was registered at clinicaltrials.gov (NCT03269955).
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Pancreaticoduodenectomy (PD) is the standard surgical procedure for periampullary disease, and it is one of the most complex procedures in gastroenterological surgery. The rate of mortality is less than 4% according to the recent report, and it is reported to be about 1% in large volume centers (including our institution) through improvement of surgical techniques and postoperative management [1, 2]. However, morbidity of this procedure is still high, ranging from 30 to 40% [3, 4]. The complication rate of PD is higher than that of other operations, and this high morbidity is mainly attributable to the occurrence of postoperative pancreatic fistula (POPF) [5]. Pancreatico-enteric anastomosis is the most difficult step in PD, and POPF is caused by the procedure itself as well as other related factors, such as age, obesity, estimated blood loss, friability of pancreatic parenchyma, and size of pancreatic duct [6,7,8,9].
Since pancreatico-enteric anastomosis is developed, many materials have been proposed to reduce POPF [10, 11]. However, no innovative solution to definitively reduce the incidence of POPF has been invented. Although fibrin sealant patches were approved for targeted bleeding coverage, previous studies have shown additional beneficial results in sealing off air leaks of the trachea, thereby sealing off alveolar air leakage and reducing the incidence of lymphoceles after pelvic surgery, and decreasing cerebrospinal fluid leaks after neurosurgery [12,13,14,15,16,17]. In pancreatic surgery, methods using combined fibrin sealants and topical glue were also studied [18,19,20]. Mita et al. [18] reported in a retrospective single-arm study that 40 patients to whom fibrin sealants were applied showed a 20% reduction in the incidence of POPF compared with a previous study. Chirletti et al. [19] compared 27 patients using fibrin sealants and 27 control patients. There was no significant difference between the two groups, but the authors nevertheless reported the possibility of improving POPF with fibrin sealants. Recently, Schindl et al. [20] reported a randomized clinical trial on the effect of a fibrin sealant patch on pancreatic fistula formation after PD, and the results showed that use of a fibrin sealant patch did not reduce the occurrence of POPF and other complications.
Our institution has empirically used fibrin sealant patches on pancreatico-enteric anastomosis during PD, and we still question its utility. We believed that we could clearly determine the effects of fibrin sealant patches because pancreatico-enteric anastomosis is performed uniformly at our institution. Therefore, we planned a randomized clinical trial to investigate the efficacy of fibrin sealant patches for preventing POPF. We hypothesized that POPF rates would be lower in the fibrin sealant patch group. The purpose of this study was to evaluate the effectiveness of fibrin sealant patch application to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF.
Materials and methods
We enrolled consecutive patients who underwent pancreaticoduodenectomy in the Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery at Asan Medical Center between February 2017 and May 2018. This study was designed as a single-center, prospective, randomized, parallel-group, phase IV, single-blind (participant) trial involving three pancreaticobiliary surgeons, each with annual frequency of more than 70 PD cases. The study protocol was approved by the institutional research review board, and written informed consent was obtained from each enrolled patient. This study was registered at clinicaltrials.gov (NCT03269955), was conducted in accordance with the Declaration of Helsinki, and was performed according to CONSORT guidelines [21].
Inclusion and exclusion criteria
Included in this study were patients who were scheduled for open PD with periampullary cancer or borderline tumor, without a history of chronic pancreatitis or distant metastasis. Age ranged from 19–80 years. ECOG performance score was 0–2. Blood cell count was at least 3000/mm3, absolute neutrophil count at least 1500/mm3, and platelet count was at least 125,000/mm3. AST and ALT were less than 3 times upper limit of normal. Creatinine was no greater than 1.5 times upper limit of normal. These patients were excluded if there was an abnormality in these tests because there may be other diseases that could not be identified before surgery and the possibility of affecting patient recovery period and hospital cost. Patients had the ability to ask any questions to enhance understanding, and the willingness to sign a written informed consent document. Patients with distant metastases, recurred tumors, pregnancy, breastfeeding, active or uncontrolled infection, and uncontrolled heart disease were not eligible. Patients with moderate or severe comorbidities who were thought to be impacted in regard to quality of life or nutritional status (liver cirrhosis, chronic kidney failure, heart failure, and others) were also excluded. Patients who had undergone other major abdominal surgeries were also excluded.
Surgical technique
Resection methods during PD in our institution have been reported previously [22]. After resection in all cases, we performed pancreaticojejunostomy for pancreatico-enteric anastomosis. Pancreaticojejunostomy was carried out using the double-layered, end-to-side duct-to-mucosa method. First, we sutured the jejunum and posterior wall of the pancreas parenchyma with polypropylene suture 4-0. After that, we made a small hole in the mucosa with electrocautery. Suture of jejunal mucosa to the pancreas duct was performed with polydioxanone 5-0, with interrupted sutures. A polyethylene internal stent was inserted in the pancreatic duct of all patients, both intervention and control groups. Finally, sutures were placed between the jejunum and the anterior wall of the pancreas parenchyma with prolene 4-0. End-to-side choledochojejunostomy was also performed. Antecolic duodenojejunostomy or gastrojejunostomy with jejunojejunostomy was performed. Two closed suction drains were placed at the superior and inferior borders of pancreaticojejunostomy site. All three surgeons used the same pancreaticojejunostomy method.
Intervention
In patients randomized to the intervention group, pancreaticojejunostomy was covered with a 9.5 cm × 4.8 cm fibrinogen/thrombin-coated collagen patch (TachoSil®; Takeda Austria, Linz, Austria) on the front and back aspects of the anastomosis site. After this, fibrin glue was applied to the pancreaticojejunostomy site in PD. Only fibrin glue alone was applied to the pancreaticojejunostomy site in the control group. Feature of intervention is shown in Fig. 1.
Outcome
Primary outcome measures
-
a.
Incidence of pancreatic fistula
The evaluation of pancreatic fistula was based on the International Study Group of Pancreatic Fistula (ISGPF) [23]. According to their criteria, pancreatic fistula were evaluated by measuring the amylase level of the drain tube on postoperative day 3, and the pancreatic fistula was judged to be present when the amylase level was 3 times higher than the normal level of amylase in the blood.
- b.
Incidence of clinically relevant pancreatic fistula
The grade uses ISGPF grading, while grades B and C are clinically relevant pancreatic fistulas. According to ISGPF definition [23], maintenance drain for more than 3 weeks, clinically relevant change in management of POPF, intervention for POPF, and sign of infection without organ failure were defined as POPF grade B. POPF grade C was defined as reoperation, organ failure, or death related to POPF.
Secondary outcome measures
- a.
Incidence of complications
Complications other than pancreatitis included all complications after PD. Delayed gastric emptying and postoperative bleeding complied with the criteria of the International Study Group, and the severity of complications was classified through the Clavien–Dindo classification [24].
- b.
Drainage removal days
The timing of drain tube removal was determined based on the time of removal of the last drain tube. The removal of the drain tube was assessed at the discretion of the surgeon.
- c.
Death
Any patients who died during hospitalization were noted. One patient died within 90 days of discharge; this result included death.
- d.
Readmission rate
Readmission rates included all cases of readmission after discharge due to problems associated with PD. Readmissions not related to PD were not included.
- e.
Period of hospitalization after surgery
The duration of the hospital stay was calculated based on the time when the specific patient was discharged.
- f.
Cost
The assessment of costs was defined as the total cost of care from the time of admission for surgery until discharge. Fibrin sealant patch was priced at 349 dollars in South Korea. The cost of the fibrin sealant patch used in this study was not billed to the patient.
Sample size
We assumed that 20% of the patients undergoing PD with pancreaticojejunostomy would develop a biochemical leakage (BL) or POPF after surgery, based on previous studies [18, 22, 25]. Furthermore, a 15% reduction in BL or POPF was considered to be a significant clinical improvement using a fibrin sealant patch. Based on this hypothesis, a sample size of 112 patients, 56 in each group, was calculated based on type 1 error α = 0.05 and power (1 − β) = 0.8, using a two-sided χ2 test. Factoring in a dropout rate of 10%, we recruited a total of 126 patients, 63 per each group.
Randomization
We enrolled 63 patients in each group, and a total of 126 patients were randomized with block randomization before surgery. Block randomization was performed to correct the imbalance in the number of groups. A was assigned to the intervention group, and B was assigned to the control group; the groups were then determined as: (1) ABBA, (2) BBAA, (3) ABAB, (4) BABA, (5) AABB, and (6) BAAB. Patients were randomized by an independent researcher at Asan Medical Center. The blocks were selected based on the number on thrown dice.
Statistical analysis
Statistical analyses were performed using SPSS 21.0 (IBM Corp., Armonk, NY, USA). Continuous variables were compared using Student’s t test. Categorical variables were compared with the Chi-square test, Fisher’s exact test, or by linear association. The tests were two-sided, and p value ≤ 0.05 was considered significant. Risk factors for the occurrence of BL or POPF were tested in a multivariable logistic regression with background elimination model, with results expressed as odds ratios with 90% confidence intervals. The significance level for variable elimination was 0.05.
Results
Patient recruitment started from February 2017–May 2018, and follow-up ended in December 2018. In total, 126 patients who underwent PD were included in the study, with 62 patients in the intervention group and 64 patients in the control group (Fig. 2). Two patients in the control group who did not undergo PD were excluded from this study; one underwent total pancreatectomy due to positive resection margin on intraoperative consultation diagnosis from the remnant pancreas; the other underwent palliative bile duct resection. There was no follow-up of these patients. The study, therefore, evaluated a total of 124 patients, with 62 in the intervention group and 62 in the control group. Each of three surgeons operated 30, 36, and 58 patients. Age, sex, body mass index, concurrent vein resection, disease characteristics, pancreatitis, pancreas duct size, pancreas texture, alternative fistula risk score [26], operation time, estimated blood loss, and neoadjuvant chemotherapy were not statistically different between two groups (Table 1).
Primary outcomes
BL or POPF occurred in 16 patients (25.8%) in the intervention group and in 23 patients (37.1%) in the control group (Table 2). Occurrence rates were different, but there was no statistically significant difference between the two groups. Clinically relevant POPF occurred in 4 patients (6.5%) in the intervention group, as well as in 4 patients in the control group (p = 1.000). According to the alternative fistula risk score grade, there was also no difference in the proportion of POPF between the low-, intermediate-, and high-risk patients between the two groups.
Secondary outcomes
There were no significant differences in postoperative outcomes (Table 3). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not different between the two groups. The complication rate was not different between the two groups (p = 0.506). By limiting to Clavien–Dindo class 3 or higher, there was no difference between the intervention and control groups (4.8% vs. 9.7%, p = 0.491). There was one mortality case in the control group. POPF grade C occurred in this patient, and the patient expired because of septic shock, with two reoperations at postoperative day 43. Of the total patients, reoperation occurred only in the case of the patient who died. The control group patient who underwent angioembolization due to superior mesenteric artery pseudoaneurysm with intensive care belonged to Clavien–Dindo grade 4. Readmission rate (12.9% vs. 11.3%, p = 1.000) and cost ($13,549 vs. $15,038, p = 0.103) were not different between the two groups.
Risk factors for POPF
A multivariable logistic regression model identified age (p = 0.028) and soft pancreas texture (p < 0.001) as independent risk factors for BL or POPF in the current study (Table 4). Applying fibrin sealant patch did not indicate a negative risk factor for BL or POPF, but the p value was 0.084.
Discussion
Various studies are being performed to reduce POPF after pancreatectomy. These studies include anastomosis methods, stump closure methods, and various products used after anastomosis. The mechanism of action of fibrin sealant patches is based on the interaction between active biological substances (human fibrinogen and human thrombin) and the physiology of fibrin clot formation. There were several studies on the use of fibrin sealant patches for preventing POPF after distal pancreatectomy [27,28,29,30,31]. Silvestri et al. [30] reported that use of fibrin sealant patches seems to be associated with a lower incidence of POPF grade C. Two previous multicenter, randomized controlled trials reported that fibrin sealant patches had no significant effect on the rate of POPF after distal pancreatectomy [28, 29]. For pancreaticojejunostomy, there were three studies on fibrin sealant patches. Two retrospective studies reported that fibrin sealant patches are feasible and safe with 7.4–20% POPF rates after PD with pancreaticojejunostomy [18, 19]. Schindl et al. [20] reported a multicenter, randomized clinical trial of the effect of a fibrin sealant patch after PD, and that study was the first randomized clinical trial on the fibrin sealant patch. In that study, rates of BL or POPF were 63% in the intervention group and 56% in the control group. Clinically relevant POPF rates were 23% in the intervention group and 14% in the control group. The study reported that there was no POPF reduction with the use of fibrin sealant patches after PD, but they could not provide a conclusive explanation of the higher incidence of BL.
The results of our study are reliable when compared with previous reports. BL or POPF occurred in 39 patients (31.5%), and POPF B or C occurred in 8 patients (6.5%) of the patients enrolled in our current study. The acceptable incidence of BL and POPF could be explained by each surgeon’s experience. All three surgeons participating in the study had experience in performing more than 400 PD cases, and performing more than 70 PD cases per year. All of the surgeons used the same pancreaticojejunostomy methods, and the occurrence rate of clinically relevant POPF was not different between the three surgeons (8.6% vs. 3.3% vs. 5.6%, p = 0.537). This eliminates the variability in the type of anastomosis method as a potential confounding variable and increases the internal validity of fibrin sealant efficacy. Berger et al. also described that the limitations in their dual institution comparative study were the institutional differences in surgical procedures and POPF rate [32].
Nevertheless, the current study has shown no statistically significant superiority of using fibrin sealant patches regarding incidence of BL or POPF after PD with pancreaticojejunostomy. Although there was no statistical difference, the incidence of BL was lower in the intervention group (19.4% vs. 30.6%), suggesting that the BL rate may vary if more patients are included. Additionally, in multivariable analysis of risk factors, the p value was 0.084 when the fibrin sealant patch was applied, but it was not completely meaningless because the number of patients in this study was not sufficient to perform the risk factor analysis.
There were no reductions in hospital stay, drain removal days, complications, readmission rates, and hospital expenses in patients with application of fibrin sealant patches. These results are probably because of the same incidence of clinically relevant POPF and grade 3 or higher complications between the two groups. These results were also found in another randomized clinical trial that studied fibrin sealant patches after pancreatectomy [20, 31]. The complication rate of the current study was also acceptable when compared with other studies [32, 33]. Berger et al. reported a randomized clinical trial of pancreaticojejunostomy after PD with 51.8% overall morbidity and 18.3% major complications [32]. Miyauchi et al. [33] reported 31.7% of Clavien–Dindo grade 3 of higher cases with complications after PD. In the current study, there were 62 cases (50%) of overall morbidity and 9 cases (7.3%) of grade 3 or higher complications after PD. Low incidence of major complications also can be explained by the accumulation of experience. Our institution reported a chronologic change of clinicopathologic feature after pancreatectomy for pancreatic ductal adenocarcinoma [34]. In the study, there is a statistical difference in complication rates between early periods and the last 7-year period.
The risk factors for BL or POPF were age and soft pancreas texture in our study. Age, vein resection, disease, pancreatitis, and pancreas texture were significant risk factors in univariate analysis, but age and pancreas texture were risk factors for POPF in multivariate analysis. Several studies reported that soft pancreas texture was associated with clinically relevant POPF [6, 35, 36]. Wang et al. [9] reported that POPF occurs more frequently in elderly patients, patients with cystic neoplasms, or patients with an episode of acute pancreatitis during pancreas enucleation. There was a randomized clinical trial that reported that use of polyglycolic acid mesh is associated with a significantly reduced rate of clinically relevant POPF after distal pancreatectomy [37], but to our knowledge, there was no study published on fibrin sealant patches as a negative risk factor to reduce BL or POPF. Although the incidences of clinical relevant POPF were 6.5% in both groups, the incidence of BL was not statistically significant, but there was a still difference in the current study. As we mentioned above, although applying fibrin sealant patch is not a negative risk factor, the p value may indicate a likelihood of reducing the incidence of BL. A p value of less than 0.1 may be interpreted as statistically significant when the number of enrolled patients is not sufficient. Therefore, our results suggest that studies including more number of patients are needed to clearly identify the efficacy of the fibrin sealant patch for preventing BL.
The first limitation of this study was the potential for it to be underpowered. As it was designed to be conducted at a single institution in a short period, and considering the recruitment capacity, it was designed to have 80% power. Risk factor interpretation was limited because the number of cases was not large. More clear conclusion about the effects of fibrin sealant patch is needed through multicenter randomized clinical trial involving a large number of patients. In addition, this study did not show the positive effects of the fibrin sealant, but if all studies reported only positive findings, future research and practice would be biased.
This study is also meaningful because the application of fibrin sealant suggested the possibility of reducing BL and experienced surgeons performed the same method of pancreaticojejunostomy with or without fibrin sealant patches, eliminating potential confounding variables, and yielding acceptable POPF and complication rates.
In summary, fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF and postoperative complications in this randomized study.
References
Sohn TA, Yeo CJ, Cameron JL et al (2003) Pancreaticoduodenectomy: role of interventional radiologists in managing patients and complications. J Gastrointest Surg 7:209–219
Conlon KC, Labow D, Leung D et al (2001) Prospective randomized clinical trial of the value of intraperitoneal drainage after pancreatic resection. Ann Surg 234:487–493 discussion 493–484
Kimura W, Miyata H, Gotoh M et al (2014) A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg 259:773–780
Kim CG, Jo S, Kim JS (2012) Impact of surgical volume on nationwide hospital mortality after pancreaticoduodenectomy. World J Gastroenterol 18:4175–4181
Senda Y, Shimizu Y, Natsume S et al (2018) Randomized clinical trial of duct-to-mucosa versus invagination pancreaticojejunostomy after pancreatoduodenectomy. Br J Surg 105:48–57
Pratt WB, Callery MP, Vollmer CM Jr (2008) Risk prediction for development of pancreatic fistula using the ISGPF classification scheme. World J Surg 32:419–428. https://doi.org/10.1007/s00268-007-9388-5
Jang M, Park HW, Huh J et al (2018) Predictive value of sarcopenia and visceral obesity for postoperative pancreatic fistula after pancreaticoduodenectomy analyzed on clinically acquired CT and MRI. Eur Radiol. https://doi.org/10.1007/s00330-018-5790-7
Shamali A, Shelat V, Jaber B et al (2017) Impact of obesity on short and long term results following a pancreatico-duodenectomy. Int J Surg 42:191–196
Wang X, Tan CL, Zhang H et al (2018) Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: a single-center experience of 142 patients. J Surg Oncol 117:182–190
Singh AN, Pal S, Mangla V et al (2018) Pancreaticojejunostomy: Does the technique matter? A randomized trial. J Surg Oncol 117:389–396
El Nakeeb A, El Hemaly M, Askr W et al (2015) Comparative study between duct to mucosa and invagination pancreaticojejunostomy after pancreaticoduodenectomy: a prospective randomized study. Int J Surg 16:1–6
Rosato L, Ginardi A, Mondini G et al (2012) Efficacy of fleece-bound sealing system (TachoSil(R)) in delayed anterior tracheal lacerations secondary to ischemic tracheal necrosis after total thyroidectomy. Minerva Chir 67:271–275
Grimm C, Polterauer S, Helmy-Bader S et al (2018) A collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies: a randomized clinical trial. Gynecol Oncol 149:140–145
Simonato A, Varca V, Esposito M et al (2009) The use of a surgical patch in the prevention of lymphoceles after extraperitoneal pelvic lymphadenectomy for prostate cancer: a randomized prospective pilot study. J Urol 182:2285–2290
George B, Matula C, Kihlstrom L et al (2017) Safety and efficacy of TachoSil (absorbable fibrin sealant patch) compared with current practice for the prevention of cerebrospinal fluid leaks in patients undergoing skull base surgery: a randomized controlled trial. Neurosurgery 80:847–853
Itano H (2008) The optimal technique for combined application of fibrin sealant and bioabsorbable felt against alveolar air leakage. Eur J Cardiothorac Surg 33:457–460
Lopez C, Facciolo F, Lequaglie C et al (2013) Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery. Minerva Chir 68:559–567
Mita K, Ito H, Fukumoto M et al (2011) Pancreaticojejunostomy using a fibrin adhesive sealant (TachoComb) for the prevention of pancreatic fistula after pancreaticoduodenectomy. Hepatogastroenterology 58:187–191
Chirletti P, Caronna R, Fanello G et al (2009) Pancreaticojejunostomy with application of fibrinogen/thrombin-coated collagen patch (TachoSil) in Roux-en-Y reconstruction after pancreaticoduodenectomy. J Gastrointest Surg 13:1396–1398 author reply 1399–1400
Schindl M, Fugger R, Gotzinger P et al (2018) Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy. Br J Surg 105:811–819
Schulz KF, Altman DG, Moher D (2011) CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg 9:672–677
Song KB, Kim SC, Hwang DW et al (2015) Matched case–control analysis comparing laparoscopic and open pylorus-preserving pancreaticoduodenectomy in patients with periampullary tumors. Ann Surg 262:146–155
Bassi C, Marchegiani G, Dervenis C et al (2017) The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161:584–591
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213
Callery MP, Pratt WB, Kent TS et al (2013) A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg 216:1–14
Mungroop TH, van Rijssen LB, van Klaveren D et al (2019) Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): design and international external validation. Ann Surg 269:937–943
Huttner FJ, Mihaljevic AL, Hackert T et al (2016) Effectiveness of Tachosil((R)) in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis. Langenbecks Arch Surg 401:151–159
Park JS, Lee DH, Jang JY et al (2016) Use of TachoSil((R)) patches to prevent pancreatic leaks after distal pancreatectomy: a prospective, multicenter, randomized controlled study. J Hepatobiliary Pancreat Sci 23:110–117
Sa Cunha A, Carrere N, Meunier B et al (2015) Stump closure reinforcement with absorbable fibrin collagen sealant sponge (TachoSil) does not prevent pancreatic fistula after distal pancreatectomy: the FIABLE multicenter controlled randomized study. Am J Surg 210:739–748
Silvestri S, Franchello A, Gonella F et al (2015) Role of TachoSil(R) in distal pancreatectomy: a single center experience. Minerva Chir 70:175–180
Montorsi M, Zerbi A, Bassi C et al (2012) Efficacy of an absorbable fibrin sealant patch (TachoSil) after distal pancreatectomy: a multicenter, randomized, controlled trial. Ann Surg 256:853–859 discussion 859–860
Berger AC, Howard TJ, Kennedy EP et al (2009) Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? A randomized, prospective, dual-institution trial. J Am Coll Surg 208:738–747 discussion 747–739
Miyauchi Y, Furukawa K, Suzuki D et al (2018) Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: a randomized, controlled trial. Int J Surg 61:69–75
Shin SH, Kim SC, Song KB et al (2018) Chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma since 2000: a single-center experience with 2,029 patients. Surgery 164:432–442
Akgul O, Merath K, Mehta R et al (2018) Postoperative pancreatic fistula following pancreaticoduodenectomy—stratification of patient risk. J Gastrointest Surg. https://doi.org/10.1007/s11605-018-4045-x
Petrova E, Lapshyn H, Bausch D et al (2018) Risk stratification for postoperative pancreatic fistula using the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery. Pancreatology. https://doi.org/10.1016/j.pan.2018.11.008
Jang JY, Shin YC, Han Y et al (2017) Effect of polyglycolic acid mesh for prevention of pancreatic fistula following distal pancreatectomy: a randomized clinical trial. JAMA Surg 152:150–155
Acknowledgements
This study was supported by a grant from Asan Institute for Life Science.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests in relation to this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kwon, J., Shin, S.H., Lee, S. et al. The Effect of Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil®) Application in Pancreaticojejunostomy for Prevention of Pancreatic Fistula After Pancreaticoduodenectomy: A Randomized Clinical Trial. World J Surg 43, 3128–3137 (2019). https://doi.org/10.1007/s00268-019-05172-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-019-05172-y