Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection.
ABSTRACT: INTRODUCTION: Post-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery. METHODS: A comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration. RESULTS: Seven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6-1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18-1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25-1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay. CONCLUSION: On the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection.
Project description:Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.
Project description:Blood loss remains a major concern during surgery and can increase the morbidity of the intervention. The use of topical haemostatic agents to overcome this issue therefore becomes necessary. Fibrin sealants are promising haemostatic agents due to their capacity to promote coagulation, but their effectiveness and applicability need to be improved. We have compared the haemostatic efficacy of a novel nanostructured fibrin-agarose hydrogel patch, with (c-NFAH) or without cells (a-NFAH), against two commercially available haemostatic agents in a rat model of hepatic resection. Hepatic resections were performed by making short or long incisions (mild or severe model, respectively), and haemostatic agents were applied to evaluate time to haemostasis, presence of haematoma, post-operative adhesions to adjacent tissues, and inflammation factors. We found a significantly higher haemostatic success rate (time to haemostasis) with a-NFAH than with other commercial haemostatic agents. Furthermore, other relevant outcomes investigated were also improved in the a-NFAH group, including no presence of haematoma, lower adhesions, and lower grades of haemorrhage, inflammation, and necrosis in histological analysis. Overall, these findings identify a-NFAH as a promising haemostatic agent in liver resection and likely in a range of surgical procedures.
Project description:BACKGROUND:Post-operative pancreatic fistula (POPF) remains a critical complication after pancreatic resection. This prospective pilot study evaluates perioperative markers of pancreatitis and systemic inflammation to predict clinically relevant grade B/C-POPF (CR-POPF). METHODS:All patients undergoing pancreatic resection from December 2017 to April 2019 were prospectively enrolled. Surgical procedures and outcomes were correlated with perioperative blood markers. ROC analysis was performed to assess their predictive value for CR-POPF. Cut-offs were calculated with the Youden index. RESULTS:In total, 70 patients were analysed (43 pancreatoduodenectomies and 27 distal pancreatectomies). In-hospital/90-d mortality and morbidity were 5.7/7.1% (n?=?4/n?=?5) and 75.7% (n?=?53). Major complications (Clavien-Dindo???3a) occurred in 28 (40.0%) patients, CR-POPF in 20 (28.6%) patients. Serum lipase (cut-off?>?51U/L) and IL-6 (>?56.5 ng/l) on POD3 were significant predictors for CR-POPF (AUC?=?0.799, 95%-CI 0.686-0.912 and AUC?=?0.784, 95%-CI 0.668-0.900; combined AUC?=?0.858, 95%-CI 0.758-0.958; all p?<?0.001). Patients with both or one factor(s) above cut-off more frequently developed CR-POPF than cases without (100 vs. 50% vs. 7.5%, p?<?0.001). This also applied for overall and severe complications (p?=?0.013 and p?=?0.009). CONCLUSIONS:Post-operative pancreatitis and inflammatory response are major determinants for development of POPF. A combination of serum lipase and IL-6 on POD3 is a highly significant early predictor of CR-POPF and overall complications, potentially guiding patient management. CLINICAL TRIAL REGISTRATION:The study protocol was registered at clinicaltrials.gov (NCT04294797).
Project description:BACKGROUND: Irradiation therapy is being evaluated widely as an adjunct to therapy of resectable and unresectable pancreatic exocrine carcinoma. Exsanguinating haemorrhage has been an occasional late complication. CASE OUTLINES: Two patients with unresectable cancer of the pancreas were treated by bypass, chemotherapy and both intra-operative and postoperative irradiation. Both patients died 5-11 months later of gastroduodenal haemorrhage from arterio-enteric fistulas, which were confirmed by autopsy but had been uncontrolled by selective embolisation. A third patient, for whom little other information was available, died of upper abdominal haemorrhage 5 months after a 'curative' resection combined with intra-operative and postoperative irradiation. DISCUSSION: Judgement in management is difficult because of the poor prognosis from the underlying disease on the one hand versus the fact that site of bleeding has sometimes been from complicating benign disease. Better endovascular techniques of control of such haemorrhage may be developing.
Project description:Postoperative pancreatic fistula (POPF) is a common complication following distal pancreatectomy (DP). However, the risk factors of this complication in patients after DP still remain controversial. The aim of our study is to estimate the association between potential risk factors and POPF. Relevant articles published up to June 21, 2016 were identified via PubMed, EMBASE, Web of Science, and The Cochrane Library. Studies that examined the risk factors of POPF following DP were enrolled. 20 articles (2070 patients) were finally included in this study. The pooled data suggested that patients with soft pancreas, higher Body Mass Index (BMI), blood transfusion, elevated intraoperative blood loss, and longer operative time had a decreased risk for POPF. However, age, gender, malignant pathology, types of stump closure, octreotide therapy, history of diabetes and chronic pancreatitis, splenectomy, multiorgan resection, main duct ligation, preoperative serum albumin levels, PGA felt wrapping, and extended lymphadenectomy could not be regarded as risk factors for POPF. Our analytic data demonstrated that pancreas texture, BMI, blood transfusion, intraoperative blood loss, and operative time were clinical predictor for POPF. This study may assist surgeons to screen patients with high risk of POPF and select appropriate treatment measures.
Project description:The feasible of minimally invasive pancreaticoduodenectomy (MIPD) remains controversial when compared with open pancreaticoduodenectomy (OPD). We conducted a systemic review and meta-analysis to summarise the available evidence to compare MIPD vs OPD. We systemically searched PubMed, EMBASE and Web of Science for studies published through February 2016. The primary endpoint was postoperative pancreatic fistula (POPF, grade B/C). A total of 27 studies involving 14,231 patients (2,377 MIPD and 11,854 OPD) were included. MIPD was associated with longer operative times (P?<?0.01) and increased mortality (P?<?0.01), but decreased estimated blood loss (P?<?0.01), decreased delayed gastric emptying (P?<?0.01), increased R0 resection rate (P?<?0.01), decreased wound infection (P?=?0.03) and shorter hospital stays (P?<?0.01). There were no significant differences in BMI (P?=?0.43), tumor size (P?=?0.17), lymph nodes harvest (P?=?0.57), POPF (P?=?0.84), reoperation (P?=?0.25) and 5-year survival rates (P?=?0.82) for MIPD compared with OPD. Although there was an increased operative cost (P?<?0.01) for MIPD compared with OPD, the postoperative cost was less (P?<?0.01) with the similar total costs (P?=?0.28). MIPD can be a reasonable alternative to OPD with the potential advantage of being minimally invasive. However, MIPD should be performed in high-volume centers and more randomized-controlled trials are needed to evaluate the appropriate indications of MIPD.
Project description:Importance:In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited. Objective:To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. Design, Setting, and Participants:This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017. Exposures:Pancreatic cancer surgery with or without NAT. Main Outcomes and Measures:Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. Results:Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P?<?.001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P?<?.001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P?<?.001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P?<?.001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P?<?.001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P?=?.66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P?=?.002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P?<?.002). Conclusions and Relevance:Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
Project description:<h4>Objectives</h4>The postoperative pancreatic fistula (POPF) is a major complication after pancreatic head resection whereby the technique of the anastomosis is a very influencing factor. The literature describes a possible protective role of the Blumgart anastomosis.<h4>Methods</h4>Patients after pancreatic head resection with reconstruction through the modified Blumgart anastomosis (a 2 row pancreatic anastomosis through mattress sutures of the parenchyma and duct to mucosa pancreaticojejunostomy, Blumgart-group) were compared with patients after pancreatic head resection and reconstruction through the conventional pancreatojejunostomy (single suture technique of capsule and parenchyma to seromuscularis, PJ-group). The Data were collected retrospectively. Depending on the propensity score matching in a ratio of 1:2 comparison groups were set up. Blumgart-group (n=29) and PJ-group (n=56). The primary end point was the rate of POPF. Secondary goals were duration of operation, length of hospital stay, length of stay on intermediate care units and hospital mortality.<h4>Results</h4>The rate of POPF (biochemical leak, POPF "grade B" and POPF "grade C") was less in the Blumgart-group, but without statistical relevance (p=0.23). Significantly less was the rate of POPF "grade C" in the Blumgart-group (p=0.03). Regarding the duration of hospital stay, length of stay on intermediate care units and hospital mortality, there was no relevant statistical difference between the groups (p=0.1; p=0.4; p=0.7). The duration of the operation was significantly less in the Blumgart-group (p=0.001).<h4>Conclusions</h4>The modified Blumgart anastomosis technique may have the potential to decrease major postoperative pancreatic fistula.
Project description:<h4>Background</h4>Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common cause of major morbidity following pancreatic resection. Intra-abdominal drains are frequently positioned adjacent to the pancreatic anastomosis or transection margin at the time of surgery to aid in detection and management of CR-POPF. Drains can either evacuate fluid by passive gravity (PG) or be attached to a closed suction (CS) system using negative pressure. There is controversy as to whether one of these two systems is superior. The objective of this review is to identify and compare the incidence of adverse events (AEs) and resource utilisation associated with PG and CS drainage following pancreatic resections.<h4>Methods and analysis</h4>MEDLINE, EMBASE, CINAHL and Cochrane Central Registry of Controlled Trials will be searched from inception to April 2019, to identify interventional and observational studies comparing PG and CS drains following pancreatic resection. The primary outcome is POPF as defined by the International Study Group for Pancreatic Fistula in 2017. Secondary outcomes include postoperative AE, resource utilisation (length of stay, return to emergency department, readmission and reintervention), time to drain removal and quality of life. Study selection, data extraction and risk of bias assessment will be performed independently, by two reviewers. A meta-analysis will be conducted if deemed statistically appropriate. Subgroup analysis by study design will be performed. Study heterogeneity will be calculated with the ?<sup>2</sup> test and reported as I<sup>2</sup> statistics. Statistical analyses will be conducted and displayed using RevMan V.5.3 ETHICS AND DISSEMINATION: Ethics approval is not required. The results of this study will be submitted to relevant conferences for presentation and peer-reviewed journals for publication.<h4>Prospero registration number</h4>CRD42019123647.
Project description:Postoperative pancreatic fistula (POPF) remains a persistent problem after pancreaticoduodenectomy (PD), especially in the presence of a soft, nonfibrotic pancreas. To reduce the risk of POPF, pancreaticogastrostomy (PG) is an optional reconstruction technique for surgeons after PD. This study presents a new technique of PG for a soft, nonfibrotic pancreas with double-binding continuous hemstitch sutures and evaluates its safety and reliability. From January 2011 to June 2012, 92 cases of patients with periampullary malignancy with a soft pancreas underwent this technique. A modified technique of PG was performed with two continuous hemstitch sutures placed in the mucosal and seromuscular layers of the posterior gastric wall, respectively. Then the morbidity and mortality was calculated. This technique was applied in 92 patients after PD all with soft pancreas. The median time for the anastomosis was 12 min (range, 8-24). Operative mortality was zero, and morbidity was 16.3 % (n?=?15), including hemorrhage (n?=?2), biliary fistula (n?=?2), pulmonary infection (n?=?1), delayed gastric emptying (DGE; n?=?5, 5.4 %), abdominal abscess (n?=?3, one caused by PF), and POPF (n?=?2, 2.2 %). Two patients developed a pancreatic fistula (one type A and one type B) classified according to the International Study Group on Pancreatic Fistula. The described technique is a simple and safe reconstruction procedure after PD, especially for patients with a soft and fragile pancreas.