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Xue K, Wang L, Chen L, Liu X, Li A, Wang Z, Hou S, Xiong J, Tian B. Development and validation of a novel pancreaticojejunostomy strategy based on the anatomical location of the main pancreatic duct that can reduce the risk of postoperative pancreatic fistula after pancreatoduodenectomy. Gland Surg 2024; 13:1693-1707. [PMID: 39544981 PMCID: PMC11558298 DOI: 10.21037/gs-24-235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 09/30/2024] [Indexed: 11/17/2024]
Abstract
Background Postoperative pancreatic fistula (POPF) is a common complication after pancreaticoduodenectomy (PD). The effect of the location of the main pancreatic duct on POPF development is not completely elucidated. This study aimed to investigate the association between the location of the main pancreatic duct and POPF, and the effect of pancreaticojejunostomy based on the location of the main pancreatic duct on the risk of POPF. Methods This retrospective study enrolled 871 patients who underwent PD between January 2018 and December 2021. Logistic regression analysis was performed to identify the independent risk factors associated with POPF. Predictive performance was evaluated using the receiver operating characteristic curves. In addition, a novel pancreaticojejunostomy strategy that could reduce the risk of POPF was adopted. Results Based on the multivariate analysis, the pancreatic texture and the location of the main pancreatic duct were the independent risk factors of POPF. A threshold ratio of 0.397 was used to distinguish the central from the eccentric pancreatic ducts. Notably, patients with the central pancreatic duct had a significantly lower incidence rate of POPF than those with the eccentric pancreatic ducts (10.6% vs. 44.8%, P<0.001). The novel group exhibited a significantly lower incidence rate of POPF than the conventional group (13.7% vs. 23.0%, P=0.02), and the incidence rate of other complications was not high. Conclusions The location of the main pancreatic duct is associated with POPF development. However, implementing the novel pancreaticojejunostomy approach can effectively reduce the risk of POPF while ensuring safety.
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Affiliation(s)
- Kang Xue
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Li Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Lang Chen
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaofeng Liu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Angzhi Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zihe Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhong Hou
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Junjie Xiong
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Bole Tian
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
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Symeonidis D, Zacharoulis D, Tzovaras G, Kissa L, Samara AA, Petsa E, Tepetes K. Stent A pancreaticojejunostomy after pancreatoduodenectomy: Is it always necessary? World J Methodol 2024; 14:90164. [PMID: 39310242 PMCID: PMC11230077 DOI: 10.5662/wjm.v14.i3.90164] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 02/19/2024] [Accepted: 04/07/2024] [Indexed: 06/25/2024] Open
Abstract
The establishment of a postoperative pancreatic fistula (POPF) is considered the most common and, concomitantly, the most serious complication associated with pancreaticoduodenectomy (PD). The search for either technical modifications of the operative technique or pharmaceutical interventions that could possibly aid in decreasing the incidence of this often-devastating complication appears justified. The stenting of the pancreatic duct, with the use of either internal or external stents, has been evaluated in this direction. In theory, it is an approach that could eliminate many pathophysiological factors responsible for the occurrence of a POPF. The purpose of the present study was to review the current data regarding the role of pancreatic duct stenting on the incidence of POPF, after PD, by using PubMed and Reference Citation Analysis. In general, previous studies seem to highlight the superiority of external stents over their internal counterparts in regard to the incidence of POPF; this is at the cost, however, of increased morbidity associated mainly with the stent removal. Certainly, the use of an internal stent is a less invasive approach with acceptable results and is definitely deprived of the drawbacks arising through the complete diversion of pancreatic juice from the gastrointestinal tract. Bearing in mind the scarcity of high-quality data on the subject, an approach of reserving stent placement for the high-risk for POPF patients and individualizing the selection between the use of an internal or an external stent according to the distinct characteristics of each individual case scenario appears appropriate.
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Affiliation(s)
| | | | - Georgios Tzovaras
- Department of Surgery, University Hospital of Larissa, Larissa 41110, Greece
| | - Labrini Kissa
- Department of Surgery, University Hospital of Larissa, Larissa 41110, Greece
| | - Athina A Samara
- Department of Surgery, University Hospital of Larissa, Larissa 41110, Greece
| | - Eleana Petsa
- Department of Surgery, University Hospital of Larissa, Larissa 41110, Greece
| | - Konstantinos Tepetes
- Department of General Surgery, University Hospital of Larissa, Larissa 41110, Greece
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Hughes DLL, Hughes A, Gordon-Weeks AN, Silva MA. Continuous drain irrigation as a risk mitigation strategy for postoperative pancreatic fistula: a meta-analysis. Surgery 2024; 176:180-188. [PMID: 38734504 DOI: 10.1016/j.surg.2024.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 01/21/2024] [Accepted: 03/18/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Postoperative pancreatic fistula serves as the principle cause for the morbidity and mortality observed after pancreatectomy. Continuous drain irrigation as a treatment strategy for infected pancreatic necrosis has previously been described; however, its role adter pancreatectomy has yet to be determined. The aim of this study was to determine whether continuous drain irrigation reduces postoperative pancreatic fistula. METHODS A meta-analysis of the pre-existing literature was performed. The primary end point was whether continuous drain irrigation reduced postoperative pancreatic fistula after pancreatectomy. The secondary end point evaluated its impact on postoperative morbidity, mortality, and length of stay. RESULTS Nine articles involving 782 patients were included. Continuous drain irrigation use was associated with a statistically significant reduction in postoperative pancreatic fistula rates (odds ratio [95% confidence interval] 0.40 [0.19-0.82], P = .01). Upon subgroup analysis, a significant reduction in clinically relevant postoperative pancreatic fistula was also noted (odds ratio 0.37 [0.20-0.66], P = .0008). A reduction in postoperative complications was also observed-delayed gastric emptying (0.45 [0.24-0.84], P = .01) and the need for re-operation (0.33 [0.11-0.96], P = .04). This reduction in postoperative complications translated into a reduced length of stay (mean difference -2.62 [-4.97 to -0.26], P = .03). CONCLUSION Continuous drain irrigation after pancreatectomy is a novel treatment strategy with a limited body of published evidence. After acknowledging the limitations of the data, initial analysis would suggest that it may serve as an effective risk mitigation strategy against postoperative pancreatic fistula. Further research in a prospective context utilizing patient risk stratification for fistula development is, however, required to define its role within clinical practice.
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Affiliation(s)
- Daniel L L Hughes
- Department of Hepatopancreaticobiliary surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
| | - Aron Hughes
- Department of Acute Medicine, University Hospital of Wales, Cardiff, United Kingdom
| | - Alex N Gordon-Weeks
- Department of Hepatopancreaticobiliary surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Michael A Silva
- Department of Hepatopancreaticobiliary surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Walber JK, Antony P, Strothmann H, Kalkum E, Renzulli P, Hauswirth F, Probst P, Muller MK. Effect of artificial or autologous coverage of the pancreatic remnant or anastomosis on postoperative pancreatic fistulas after partial pancreatectomy: meta-analysis of randomized clinical trials. BJS Open 2024; 8:zrae059. [PMID: 38814751 PMCID: PMC11138960 DOI: 10.1093/bjsopen/zrae059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/10/2024] [Accepted: 04/20/2024] [Indexed: 06/01/2024] Open
Abstract
BACKGROUND Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic remnant can reduce the incidence of postoperative pancreatic fistulas. The aim of this study was to evaluate the effect of autologous or artificial coverage of the pancreatic remnant or anastomosis on outcomes after partial pancreatectomy. METHODS A systematic literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2024. All RCTs analysing a coverage method in patients undergoing partial pancreatoduodenectomy or distal pancreatectomy were included. The primary outcome was postoperative pancreatic fistula development. Subgroup analyses for pancreatoduodenectomy or distal pancreatectomy and artificial or autologous coverage were conducted. RESULTS A total of 18 RCTs with 2326 patients were included. In the overall analysis, coverage decreased the incidence of postoperative pancreatic fistulas by 29% (OR 0.71, 95% c.i. 0.54 to 0.93, P < 0.01). This decrease was also seen in the 12 RCTs covering the remnant after distal pancreatectomy (OR 0.69, 95% c.i. 0.51 to 0.94, P < 0.02) and the 4 RCTs applying autologous coverage after pancreatoduodenectomy and distal pancreatectomy (OR 0.53, 95% c.i. 0.29 to 0.96, P < 0.04). Other subgroup analyses (artificial coverage or pancreatoduodenectomy) showed no statistically significant differences. The secondary endpoints of mortality, reoperations, and re-interventions were each affected positively by the use of coverage techniques. The certainty of evidence was very low to moderate. CONCLUSION The implementation of coverage, whether artificial or autologous, is beneficial after partial pancreatectomy, especially in patients undergoing distal pancreatectomy with autologous coverage.
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Affiliation(s)
- Jonas K Walber
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Pia Antony
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Hendrik Strothmann
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Eva Kalkum
- Study Centre of the German Society of Surgery (SDGC), University of Heidelberg, Heidelberg, Germany
| | - Pietro Renzulli
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Fabian Hauswirth
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
| | - Pascal Probst
- Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland
| | - Markus K Muller
- Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland
- Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland
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Sarfaty E, Khajoueinejad N, Zewde MG, Yu AT, Cohen NA. Surgical management of pancreatic ductal adenocarcinoma: a narrative review. Transl Gastroenterol Hepatol 2023; 8:39. [PMID: 38021357 PMCID: PMC10643215 DOI: 10.21037/tgh-23-27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 08/21/2023] [Indexed: 12/01/2023] Open
Abstract
Background and Objective Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death in the United States and is projected to become the second-leading cause of cancer-related death by 2030. Despite advances in systemic and radiation therapy, for patients with surgically resectable PDAC, complete surgical resection is the only potentially curative treatment option. The conduct of a safe, technically excellent pancreatectomy is essential to achieve optimal perioperative outcomes and long-term survival. In this narrative review, evidence from large, well-executed studies and clinical trials examining the technical aspects of pancreatectomy is reviewed. Methods A search was conducted in PubMed, Medline, and Cochrane Review databases to identify English-language randomized clinical trials, meta-analyses, and systematic reviews assessing surgical aspects of pancreatectomy for PDAC published between 2010 to 2023. Key Content and Findings We identified retrospective and prospective studies evaluating the technical aspects of surgery for PDAC. In this review, we evaluate data on surgical techniques of pancreatectomy for PDAC, including the role of minimally invasive techniques, extent of lymphadenectomy, reconstruction options after pancreatoduodenectomy, and the role of surgical drainage. Conclusions Surgical resection has a critical role in the treatment of operable PDAC. While pancreatic cancer surgery is an active area of research, conducting a technically excellent surgical resection maintains paramount importance for both oncological and perioperative outcomes. In this review, we summarize the latest evidence on surgical technique for operable PDAC.
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Affiliation(s)
- Elad Sarfaty
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Nazanin Khajoueinejad
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Makda G. Zewde
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Allen T. Yu
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Chui JN, Sahni S, Samra JS, Mittal A. Postoperative pancreatitis and pancreatic fistulae: a review of current evidence. HPB (Oxford) 2023; 25:1011-1021. [PMID: 37301633 DOI: 10.1016/j.hpb.2023.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/28/2023] [Accepted: 05/09/2023] [Indexed: 06/12/2023]
Abstract
OBJECTIVES Postoperative pancreatic fistula (POPF) represents one of the most severe complications following pancreatic surgery. Despite being a leading cause of morbidity and mortality, its pathophysiology is poorly understood. In recent years, there has been growing evidence to support the role of postoperative or post-pancreatectomy acute pancreatitis (PPAP) in the development of POPF. This article reviews the contemporary literature on POPF pathophysiology, risk factors, and prevention strategies. METHODS A literature search was conducted using electronic databases, including Ovid Medline, EMBASE, and Cochrane Library, to retrieve relevant literature published between 2005 and 2023. A narrative review was planned from the outset. RESULTS A total of 104 studies fulfilled criteria for inclusion. Forty-three studies reported on technical factors predisposing to POPF, including resection and reconstruction technique and adjuncts for anastomotic reinforcement. Thirty-four studies reported on POPF pathophysiology. There is compelling evidence to suggest that PPAP plays a critical role in the development of POPF. The acinar component of the remnant pancreas should be regarded as an intrinsic risk factor; meanwhile, operative stress, remnant hypoperfusion, and inflammation represent common mechanisms for acinar cell injury. CONCLUSIONS The evidence base for PPAP and POPF is evolving. Future POPF prevention strategies should look beyond anastomotic reinforcement and target underlying mechanisms of PPAP development.
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Affiliation(s)
- Juanita N Chui
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, Australia; Faculty of Medical and Health Sciences, The University of Sydney, Sydney, Australia
| | - Sumit Sahni
- Faculty of Medical and Health Sciences, The University of Sydney, Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
| | - Jaswinder S Samra
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, Australia; Faculty of Medical and Health Sciences, The University of Sydney, Sydney, Australia; Australian Pancreatic Centre, Sydney, Australia
| | - Anubhav Mittal
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, Australia; Faculty of Medical and Health Sciences, The University of Sydney, Sydney, Australia; Australian Pancreatic Centre, Sydney, Australia; School of Medicine, The University of Notre Dame, Sydney, Australia.
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Meierhofer C, Fuegger R, Biebl M, Schoefl R. Pancreatic Fistulas: Current Evidence and Strategy-A Narrative Review. J Clin Med 2023; 12:5046. [PMID: 37568446 PMCID: PMC10419817 DOI: 10.3390/jcm12155046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct. Therefore, treatment options and preventive measurements have become a hot topic in recent years. Studies have investigated the use of fibrin sealants, different closure methods, and less invasive surgical techniques. Treatment options consist of conservative measurements and the use of percutaneous drainage, prophylactic transpapillary stenting, and surgery in severe cases. As EUS has become widely available, transmural stenting started to influence the management of pancreatic fluid collections (PFCs). However, studies on its use for the management of pancreatic fistulas are lacking. Medical treatment options like somatostatin analogs and pasireotide have been investigated but yielded mixed results.
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Affiliation(s)
- Clara Meierhofer
- Department of Gastroenterology, Ordensklinikum Linz, 4010 Linz, Austria
| | | | - Matthias Biebl
- Department of Surgery, Ordensklinikum Linz, 4010 Linz, Austria
| | - Rainer Schoefl
- Department of Gastroenterology, Ordensklinikum Linz, 4010 Linz, Austria
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Meierhofer C, Fuegger R, Spaun GO, Wundsam HV, Kirchweger P, Biebl M, Schoefl R. Endoscopic Transmural Therapy of Pancreatic Fistulas in an Interdisciplinary Setting-A Retrospective Data Analysis. J Clin Med 2023; 12:4531. [PMID: 37445564 DOI: 10.3390/jcm12134531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/25/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
Pancreatic fistulas belong to the most feared complications after surgery on or near the pancreas, abdominal trauma, or severe pancreatitis. The majority occur in the setting of operative interventions and are called postoperative pancreatic fistulas (POPF). They can lead to various complications, including abscesses, delayed gastric emptying or hemorrhages with a significant impact on morbidity and mortality. Several risk factors have been identified, including smoking, high BMI, male gender, and age. Prophylactic measures and treatment options have been explored but with limited success. This study aimed to analyze the incidence and management of pancreatic fistulas treated in a tertiary referral center, particularly focusing on an endoscopic approach. The data of 60 patients with clinically relevant pancreatic fistulas were analyzed between 2018 and 2021. Different treatment approaches, including conservative management, percutaneous drainage, transpapillary stenting, and endoscopic transmural drainage, were evaluated. An endoscopic transmural approach using lumen-apposing metal stents (LAMS) was used in almost half of this cohort showing promising results, with a high rate of fistula closure in refractory cases and a mean time until closure of 2.7 months. The findings suggest that an endoscopic approach, particularly using LAMS, can be effective in the management of pancreatic fistulas.
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Affiliation(s)
- Clara Meierhofer
- Department of Gastroenterology, Ordensklinikum Barmherzige Schwestern Linz, 4010 Linz, Austria
| | - Reinhold Fuegger
- Department of Surgery, Ordensklinikum Linz Barmherzige Schwestern, 4010 Linz, Austria
| | - Georg O Spaun
- Department of Surgery, Ordensklinikum Linz Barmherzige Schwestern, 4010 Linz, Austria
| | | | - Patrick Kirchweger
- Department of Surgery, Ordensklinikum Linz Barmherzige Schwestern, 4010 Linz, Austria
| | - Matthias Biebl
- Department of Surgery, Ordensklinikum Linz Barmherzige Schwestern, 4010 Linz, Austria
| | - Rainer Schoefl
- Department of Gastroenterology, Ordensklinikum Barmherzige Schwestern Linz, 4010 Linz, Austria
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Lai M, Zhou S, He S, Cheng Y, Cheng N, Deng Y, Ding X. Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. Cochrane Database Syst Rev 2023; 6:CD009621. [PMID: 37335216 PMCID: PMC10291948 DOI: 10.1002/14651858.cd009621.pub5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
BACKGROUND Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020. OBJECTIVES To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness. AUTHORS' CONCLUSIONS Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.
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Affiliation(s)
- Mingliang Lai
- Department of Clinical Laboratory, Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, China
| | - Shiyi Zhou
- Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Sirong He
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yao Cheng
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Nansheng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yilei Deng
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiong Ding
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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10
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Serradilla-Martín M, Paterna-López S, Palomares-Cano A, Cantalejo-Díaz M, Abadía-Forcén T, Gutiérrez-Díez ML, Artigas-Marco C, Serrablo-Requejo A. Polyethylene glycol-coated haemostatic patch for prevention of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy: randomized clinical trial. BJS Open 2023; 7:zrad028. [PMID: 37021546 PMCID: PMC10077024 DOI: 10.1093/bjsopen/zrad028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 02/07/2023] [Accepted: 02/09/2023] [Indexed: 04/07/2023] Open
Abstract
BACKGROUND The potential of haemostatic patches to reduce the rate of postoperative pancreatic fistula remains unclear. The aim of this trial was to evaluate the impact of a polyethylene glycol-coated haemostatic patch on the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. METHODS In this randomized, single-centre, clinical trial, patients undergoing pancreatoduodenectomy were randomized 1 : 1 to receive pancreatojejunostomy reinforced with two polyethylene glycol-coated haemostatic patches (patch group) or without any reinforcement (control group). The primary outcome was clinically relevant postoperative pancreatic fistula, defined as grade B/C according to International Study Group of Pancreatic Surgery criteria, within 90 days. Key secondary outcomes were length of hospital stay, total rate of postoperative pancreatic fistula, and overall complication rate. RESULTS From 15 May 2018 to 22 June 2020, 72 patients were randomized, and 64 were included in the analyses (31 in the patch group and 33 in the control group). The risk of clinically relevant postoperative pancreatic fistula was reduced by 90 per cent (OR 0.10, 95 per cent c.i. 0.01 to 0.89, P = 0.039). Moreover, the use of the polyethylene glycol-coated patch retained its protective effect on clinically relevant postoperative pancreatic fistula in a multivariable regression model, significantly reducing the risk of clinically relevant postoperative pancreatic fistula by 93 per cent (OR 0.07, 95 per cent c.i. 0.01 to 0.67, P = 0.021), regardless of patient age, sex, or fistula risk score. The incidence of secondary outcomes did not significantly differ between the groups. One patient died within 90 days in the patch group versus three patients in the control group. CONCLUSIONS A polyethylene glycol-coated haemostatic patch reduced the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. REGISTRATION NUMBER NCT03419676 (http://www.clinicaltrials.gov).
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Affiliation(s)
- Mario Serradilla-Martín
- Department of Surgery, Instituto de Investigación Sanitaria Aragón, Miguel Servet University Hospital, Zaragoza, Spain
| | | | - Ana Palomares-Cano
- Department of Surgery, Miguel Servet University Hospital, Zaragoza, Spain
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Clinical impact of lactate on postoperative pancreatic fistula after pancreaticoduodenectomy: A single-center retrospective study of 1,043 patients. Pancreatology 2023; 23:245-250. [PMID: 36805104 DOI: 10.1016/j.pan.2023.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/29/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND/OBJECTIVES Several hemodynamic markers have been studied to predict postoperative complication which is a risk factor for poor quality of life and prognosis. The aim of this study was to determine whether postoperative lactate clearance could affect clinical outcome based on complications in one surgical patient group. METHODS We retrospectively reviewed data from all patients who underwent pancreaticoduodenectomy (PD) at Samsung Medical Center from January 2015 to December 2019. Differences in baseline characteristics of patients, intraoperative outcome, and postoperative outcome were evaluated according to the presence or absence of clinically relevant postoperative pancreatic fistula (CR-POPF). RESULTS Among a total of 1107 patients, 1043 patients were tested for arterial lactate levels immediately after surgery, and the day after surgery. Immediately postoperative hyperlactatemia (lactate ≥2.0 mmol/L) was not related to CR-POPF (P = 0.269). However, immediately postoperative hyperlactatemia with a negative lactic clearance on postoperative day (POD) 1 was related to CR-POPF (P = 0.003). In multivariate analyses, non-pancreatic cancer (hazard ratio (HR): 2.545, P < 0.001), soft pancreatic texture (HR: 1.884, P < 0.001), and postoperative hyperlactatemia with negative lactate clearance on POD 1 (HR: 1.805, P = 0.008) were independent risk factors for CR-POPF. CONCLUSIONS Hyperlactatemia with negative lactate clearance after PD, one of the high-risk surgeries requiring postoperative ICU care, is a risk factor for CR-POPF. In case of immediately postoperative hyperlactatemia after PD, lactate clearance with serial lactate level follow-up can be used for achieving the hemodynamic goal to prevent CR-POPF.
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12
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Kokkinakis S, Kritsotakis EI, Maliotis N, Karageorgiou I, Chrysos E, Lasithiotakis K. Complications of modern pancreaticoduodenectomy: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int 2022; 21:527-537. [PMID: 35513962 DOI: 10.1016/j.hbpd.2022.04.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 04/13/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND In the past decades, the perioperative management of patients undergoing pancreaticoduodenectomy (PD) has undergone major changes worldwide. This review aimed to systematically determine the burden of complications of PD performed in the last 10 years. DATA SOURCES A systematic review was conducted in PubMed for randomized controlled trials and observational studies reporting postoperative complications in at least 100 PDs from January 2010 to April 2020. Risk of bias was assessed using the Cochrane RoB2 tool for randomized studies and the methodological index for non-randomized studies (MINORS). Pooled complication rates were estimated using random-effects meta-analysis. Heterogeneity was investigated by subgroup analysis and meta-regression. RESULTS A total of 20 randomized and 49 observational studies reporting 63 229 PDs were reviewed. Mean MINORS score showed a high risk of bias in non-randomized studies, while one quarter of the randomized studies were assessed to have high risk of bias. Pooled incidences of 30-day mortality, overall complications and serious complications were 1.7% (95% CI: 0.9%-2.9%; I2 = 95.4%), 54.7% (95% CI: 46.4%-62.8%; I2 = 99.4%) and 25.5% (95% CI: 21.8%-29.4%; I2= 92.9%), respectively. Clinically-relevant postoperative pancreatic fistula risk was 14.3% (95% CI: 12.4%-16.3%; I2 = 92.0%) and mean length of stay was 14.8 days (95% CI: 13.6-16.1; I2 = 99.3%). Meta-regression partially attributed the observed heterogeneity to the country of origin of the study, the study design and the American Society of Anesthesiologists class. CONCLUSIONS Pooled complication rates estimated in this study may be used to counsel patients scheduled to undergo a PD and to set benchmarks against which centers can audit their practice. However, cautious interpretation is necessary due to substantial heterogeneity.
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Affiliation(s)
- Stamatios Kokkinakis
- Department of General Surgery, University General Hospital of Heraklion, Heraklion, Crete 71110, Greece
| | - Evangelos I Kritsotakis
- Laboratory of Biostatistics, Division of Social Medicine, School of Medicine, University of Crete, Heraklion, Crete 71110, Greece
| | - Neofytos Maliotis
- Department of General Surgery, University General Hospital of Heraklion, Heraklion, Crete 71110, Greece
| | - Ioannis Karageorgiou
- Department of General Surgery, University General Hospital of Heraklion, Heraklion, Crete 71110, Greece
| | - Emmanuel Chrysos
- Department of General Surgery, University General Hospital of Heraklion, Heraklion, Crete 71110, Greece
| | - Konstantinos Lasithiotakis
- Department of General Surgery, University General Hospital of Heraklion, Heraklion, Crete 71110, Greece.
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13
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Digestive tract reconstruction in pancreaticoduodenectomy in University Hospitals of China: a national questionnaire survey. JOURNAL OF PANCREATOLOGY 2022. [DOI: 10.1097/jp9.0000000000000106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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14
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OUP accepted manuscript. Br J Surg 2022; 109:812-821. [DOI: 10.1093/bjs/znac074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/07/2021] [Accepted: 02/23/2022] [Indexed: 11/13/2022]
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Abstract
Periampullary neoplasms are a heterogeneous group of different tumor entities arising from the periampullary region, of which pancreatic ductal adenocarcinoma (PDAC) is the most common subgroup with 60-70%. As typical for pancreatic adenocarcinomas, periampullary pancreatic cancer is characterized by an aggressive growth and early systemic progression. Due to the anatomical location in close relationship to the papilla of Vater symptoms occur at an earlier stage of the disease, so that treatment options and prognosis are overall more favorable compared to pancreatic carcinomas at other locations. Nevertheless, the principles of treatment for periampullary pancreatic cancer are not substantially different from the standards for pancreatic cancer at other locations. A potentially curative approach for non-metastatic periampullary pancreatic cancer is a multimodal therapy concept, which includes partial pancreatoduodenectomy as a radical oncological resection in combination with a systemic adjuvant chemotherapy. As a result, long-term survival can be achieved in patients with favorable prognostic factors. In addition, with the continous development of surgery and systemic treatment potentially curative treatment concepts for advanced initially nonresectable tumors were also established, after completion of neoadjuvant treatment. This article presents the current surgical principles of a radical oncological resection for periampullary pancreatic cancer in the context of a multimodal treatment concept with an outlook for future developments of treatment.
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Affiliation(s)
- Thomas Hank
- Klinik für Allgemeinchirurgie, Abteilung für Viszeralchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
| | - Ulla Klaiber
- Klinik für Allgemeinchirurgie, Abteilung für Viszeralchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
| | - Klaus Sahora
- Klinik für Allgemeinchirurgie, Abteilung für Viszeralchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
| | - Martin Schindl
- Klinik für Allgemeinchirurgie, Abteilung für Viszeralchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
| | - Oliver Strobel
- Klinik für Allgemeinchirurgie, Abteilung für Viszeralchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.
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16
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Gaspar AF, Kemp R, Sankarankutty AK, Júnior JRL, Filho JAF, Martone D, Mota GDA, Santos JSD. Clinical outcomes and costs of the use of fibrin sealant in pancreaticojejunal anastomosis after pancreaticoduodenectomy: a retrospective analysis study. Ann Med Surg (Lond) 2021; 67:102531. [PMID: 34276983 PMCID: PMC8267440 DOI: 10.1016/j.amsu.2021.102531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 06/27/2021] [Indexed: 11/18/2022] Open
Abstract
Objectives The benefits of using a fibrin sealant to reinforce the pancreaticojejunal anastomosis are still contentious, a fact that justifies the study of its effects on clinical outcomes and costs of pancreaticoduodenectomy. Methods Study of 62 consecutive patients submitted to pancreaticoduodenectomy, divided into two groups of 31 patients each: GWS = group with sealant and GWOS = group without sealant that were compared according to demographic, clinical, laboratory aspects, the incidence of postoperative pancreatic fistula (POPF), according to the definition of the International Study Group on Pancreatic Fistula, updated in 2016, and its postoperative complications categorized according to the Clavien classification, as well as hospital costs evaluated by the absorption costing method (with the exception of those related to medications). Results The groups were homogeneous and there were no significant differences in the postoperative clinical course or in the indicators of hospital care between them. Hard texture of pancreatic tissue was the only protective factor against the development of POPF (RR = 0.29 (95%CI:0,12–0,68); p = 0.005). Moreover, hospital costs were higher in GWS than in GWOS (p < 0.0001). Conclusions The use of fibrin sealant to reinforce pancreaticojejunal anastomosis did not improve the clinical and healthcare outcomes and, in addition, increased hospital costs.
Pancreaticoduodenectomy is the treatment of choice for resectable tumors of the pancreato-duodenal confluence. Morbidity rates remain high ranging between 30% and 50%. Pancreatic fistula is the most feared post pancreatic surgery complication. Studies on the effects of using fibrin sealant in pancreatic surgery are scarce and controversial.
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Affiliation(s)
- Alberto Facury Gaspar
- Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
- Corresponding author. Bandeirantes Avenue, 3900, Monte Alegre, Ribeirão Preto city, São Paulo state, Brazil.
| | - Rafael Kemp
- Division of Gastrointestinal Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Ajith Kumar Sankarankutty
- Division of Gastrointestinal Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | | | | | - Daniel Martone
- Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Gustavo de Assis Mota
- Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - José Sebastião dos Santos
- Division of Gastrointestinal Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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17
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Self-assembling peptide hydrogel SPG-178 as a pancreatic fistula-preventing agent. Langenbecks Arch Surg 2021; 407:189-196. [PMID: 34100123 DOI: 10.1007/s00423-021-02226-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/01/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE Pancreatic fistula (PF) is a common and challenging complication after pancreatic surgery. The aim of this study was to investigate the efficacy of a new method for preventing PF utilizing self-assembling peptide hydrogel SPG-178 as a preclinical study. METHODS The degradability of SPG-178 was confirmed by mixing it with protease. A PF rat model was then established to investigate the efficacy of SPG-178 at preventing PF. After transecting the pancreatic duct toward the spleen, SPG-178 was attached to both sides of the pancreatic stump. The levels of amylase and lipase in both the serum and ascites were measured and surgical specimens investigated pathologically. RESULTS The hardness of SPG-178 did not change when treated with protease over a short period. The ascitic amylase level was significantly lower in rats treated with SPG-178 than rats who were not 3 days after transection of the pancreatic duct toward the spleen. Pathological examination showed fewer inflammatory cells and presence of a structure body on the surface of the pancreatic stump in the SPG-178-treated group. SPG-178 remained on the surface and many cells that covered it formed fibrous tissue or mesothelium. CONCLUSION Self-assembling peptide hydrogel SPG-178 has potential as a tool for preventing PF.
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18
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Honselmann KC, Antoine C, Frohneberg L, Deichmann S, Bolm L, Braun R, Lapshyn H, Petrova E, Keck T, Wellner U, Bausch D. A simple nomogram for early postoperative risk prediction of clinically relevant pancreatic fistula after pancreatoduodenectomy. Langenbecks Arch Surg 2021; 406:2343-2355. [PMID: 34009458 PMCID: PMC8578094 DOI: 10.1007/s00423-021-02184-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 04/28/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. METHODS One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. RESULTS Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. CONCLUSION Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.
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Affiliation(s)
- K C Honselmann
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - C Antoine
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - L Frohneberg
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - S Deichmann
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - L Bolm
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - R Braun
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - H Lapshyn
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - E Petrova
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - T Keck
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - U Wellner
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - D Bausch
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. .,Department of Surgery, Marien Hospital Herne-University Medical Center of the Ruhr-Universität Bochum, Hölkeskampring 40, 44625, Herne, Germany.
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19
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Casciani F, Bassi C, Vollmer CM. Decision points in pancreatoduodenectomy: Insights from the contemporary experts on prevention, mitigation, and management of postoperative pancreatic fistula. Surgery 2021; 170:889-909. [PMID: 33892952 DOI: 10.1016/j.surg.2021.02.064] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/25/2021] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite abundant, high-level scientific evidence, there is no consensus regarding the prevention, mitigation, and management of clinically relevant pancreatic fistula after pancreatoduodenectomy. The aim of the present investigation is three-fold: (1) to analyze the multiple decision-making points for pancreatico-enteric anastomotic creation and fistula mitigation and management after pancreatoduodenectomy, (2) to reveal the practice of contemporary experts, and (3) to indicate avenues for future research to reduce the burden of clinically relevant pancreatic fistula. METHODS A 109-item questionnaire was sent to a panel of international pancreatic surgery experts, recognized for their clinical and scientific authority. Their practice habits and thought processes regarding clinically relevant pancreatic fistula risk assessment, anastomotic construction, application of technical adjuncts, and mitigation strategies, as well as postoperative management, was explored. Sixteen clinical vignettes were presented to reveal their certain approaches to unique situations-both common and uncommon. RESULTS Sixty experts, with a cumulative 48,860 pancreatoduodenectomies, completed the questionnaire. Their median pancreatectomy/pancreatoduodenectomy case volume was 1,200 and 705 procedures, respectively, with a median career duration of 22 years and 200 indexed publications. Although pancreatico-jejunostomy reconstruction with transperitoneal drainage is the standard operative approach for most authorities, uncertainty emerges regarding the employment of objective risk stratification and adaptation of practice to risk. Concrete suggestions are offered to inform decision-making in intimidating circumstances. Early drain removal is frequently embraced, while a step-up approach is unanimously invoked to treat severe clinically relevant pancreatic fistula. CONCLUSION A comprehensive conceptual framework of 4 sequential phases of decision-making is proposed-risk assessment, anastomotic technique, mitigation strategy employment, and postoperative management. Basic science studies and outcome analyses are proposed for improvement.
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Affiliation(s)
- Fabio Casciani
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Department of Surgery, University of Verona, Italy. https://twitter.com/F_Casciani
| | - Claudio Bassi
- Department of Surgery, University of Verona, Italy. https://twitter.com/pennsurgery
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
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20
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Serra F, Bonaduce I, Rossi EG, De Ruvo N, Cautero N, Gelmini R. The using of sealants in pancreatic surgery: A Systematic Review. Ann Med Surg (Lond) 2021; 64:102244. [PMID: 33898024 PMCID: PMC8053887 DOI: 10.1016/j.amsu.2021.102244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/15/2021] [Accepted: 03/18/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND POPF derives from the pancreatic stump, which follows pancreatic resection and the pancreatoenteric anastomosis following pancreaticoduodenectomy. Since 1978 sealants have been used in pancreatic surgery to prevent pancreatic fistula after resection of the pancreatic head and tail or for the management of trauma and the treatment of low-output pancreatic fistula. Different types of fibrin sealants have been evaluated for their potential to reduce the occurrence of POPF. METHODS A systematic search of the electronic literature was performed using PubMed, Cochrane Library, and Scopus databases to obtain access to all publications, especially clinical trials, randomised controlled trials, and systematic reviews concerning fibrin sealants pancreatic surgery. Searching for "fibrin sealants pancreas," we found a total of 73 results on Pubmed, 61 on Scopus, and 14 on Cochrane Library (148 total results). RESULTS Eighteen studies were found on literature, following the criteria already described, concerning the use of fibrin sealants in pancreatic surgery. All articles described were published in the period between 1989 and 2019.Most of these were single centre studies. A total of 1032 patients were enrolled in this review. In the studies, sealants were used to reinforce pancreatic anastomoses and for the occlusion of the main pancreatic duct. CONCLUSION CR-POPF is a fearful complication of pancreatic surgery; among the possible solutions to reduce the risk of onset, sealants were used on the pancreatic stump; today the sealants should be considered such as an option to reduce the CR-POPF, but the routine use in clinical practice has to be validated.
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Affiliation(s)
- Francesco Serra
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
| | - Isabella Bonaduce
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
| | - Elena Giulia Rossi
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
| | - Nicola De Ruvo
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
| | - Nicola Cautero
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
| | - Roberta Gelmini
- Department of Surgery, University of Modena and Reggio Emilia, Policlinico of Modena, Via del Pozzo, 71 41100, Modena, Italy
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21
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Iwamoto K, Saito T, Takemoto Y, Ueno K, Yanagihara M, Furuya-Kondo T, Kurazumi H, Tanaka Y, Taura Y, Harada E, Hamano K. Autologous transplantation of multilayered fibroblast sheets prevents postoperative pancreatic fistula by regulating fibrosis and angiogenesis. Am J Transl Res 2021; 13:1257-1268. [PMID: 33841654 PMCID: PMC8014429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 01/11/2021] [Indexed: 06/12/2023]
Abstract
INTRODUCTION Postoperative pancreatic fistula (POPF) is a serious complication after gastrointestinal or pancreatic surgery. Despite intensive investigations, the occurrence has not significantly decreased in the past decades. The aims of this study were to clarify the pathophysiology of POPF and establish the preventive measures using multilayered fibroblast sheets. METHODS We developed a pancreatic fistula (PF) model of rat with transection of the splenic duct and surrounding pancreatic parenchyma. Multilayered fibroblast sheets prepared from tails were autologously transplanted to this model. The preventive effect was biochemically and histologically evaluated by measuring the ascitic levels of pancreatic enzymes and conducting immunohistochemistry and real-time polymerase chain reaction analyses of pancreatic tissue. Findings were compared to those obtained with acellular materials simply sealing the wound. RESULTS In the PF model, the ascitic levels of pancreatic enzymes were transiently up-regulated. Inflammation and necrosis were histologically observed in a wide range. Islets were damaged even in remote areas. Transplantation of multilayered fibroblast sheets dramatically reduced the ascitic leakage of enzymes, suppressed inflammation, and broadly preserved the islets. Compared with acellular materials, these sheets offered superior prevention of cellular activity through the spaciotemporal regulation of fibrosis and angiogenesis. Notably, the leakage hole appeared to have been plugged with the fibrotic matrix, which might have been the most crucial mechanism minimizing pancreatic damage. CONCLUSIONS The autologous transplantation of multilayered fibroblast sheets significantly prevented PF and protected the pancreas, underscoring the potential utility of this approach for POPF prevention.
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Affiliation(s)
- Keisuke Iwamoto
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Toshiro Saito
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Yoshihiro Takemoto
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Koji Ueno
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Masashi Yanagihara
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Tomoko Furuya-Kondo
- Department of Molecular Pathology, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Hiroshi Kurazumi
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Yuya Tanaka
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Yohei Taura
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Eijiro Harada
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
| | - Kimikazu Hamano
- Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineYamaguchi, Japan
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22
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Gasteiger S, Primavesi F, Werkl P, Dostal L, Gehwolf P, Braunwarth E, Maglione M, Sopper S, Öfner D, Stättner S. The prognostic value of Presepsin for postoperative complications following pancreatic resection: A prospective study. PLoS One 2020; 15:e0243510. [PMID: 33296435 PMCID: PMC7725319 DOI: 10.1371/journal.pone.0243510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 11/22/2020] [Indexed: 11/18/2022] Open
Abstract
Background Presepsin is involved in binding lipopolysaccharides and previous studies have confirmed its value as a marker for early diagnosis and prediction of severity in sepsis. Comparable studies assessing the predictive potential regarding postoperative complications and mortality following pancreatic resection are lacking. Methods This prospective study included 70 patients undergoing pancreatic resection from December 2017 until May 2019. Presepsin was measured preoperatively, on postoperative day 1, 3 and 8 (POD1/3/8) and correlated with the clinical course and mortality. Results Severe complications (Clavien-Dindo ≥3a) occurred in 28 patients (40%), postoperative pancreatic fistula (POPF) grade B/C occurred in 20 patients (28.6%), infectious complications in 28 (40%), and four patients (5.7%) died during hospital stay. Presepsin levels at any timepoint did not correlate with further development of postoperative complications or in-hospital mortality whereas CRP levels on postoperative day (POD) 3 were significantly associated with clinically relevant POPF (AUC 0.664, 95%CI 0.528–0.800; p = 0.033). Preoperative Presepsin levels as well as Presepsin on POD1 were significantly elevated in patients with malignant compared to benign underlying disease (299pg/ml vs. 174pg/ml and 693.5pg/ml vs. 294pg/ml; p = 0.009 and 0.013, respectively). Conclusion In our cohort, Presepsin was not eligible to predict the postoperative course following pancreatic resection. However, Presepsin levels were significantly elevated in patients with malignant disease, this finding warrants further investigation.
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Affiliation(s)
- Silvia Gasteiger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Peter Werkl
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Lucie Dostal
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Philipp Gehwolf
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eva Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Sieghart Sopper
- Department of Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Salzkammergut Klinikum, Vöcklabruck, Austria
- * E-mail:
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Effect of Flowable Thrombin-Containing Collagen-Based Hemostatic Matrix for Preventing Pancreatic Fistula after Pancreatectomy: A Randomized Clinical Trial. J Clin Med 2020; 9:jcm9103085. [PMID: 32987876 PMCID: PMC7601002 DOI: 10.3390/jcm9103085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/16/2020] [Accepted: 09/21/2020] [Indexed: 01/08/2023] Open
Abstract
Background: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy. Methods: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. Results: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453–207.870, p = 0.024). Conclusion: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.
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Gasteiger S, Primavesi F, Göbel G, Braunwarth E, Cardini B, Maglione M, Sopper S, Öfner D, Stättner S. Early Post-Operative Pancreatitis and Systemic Inflammatory Response Assessed by Serum Lipase and IL-6 Predict Pancreatic Fistula. World J Surg 2020; 44:4236-4244. [PMID: 32901324 PMCID: PMC7599180 DOI: 10.1007/s00268-020-05768-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2020] [Indexed: 02/06/2023]
Abstract
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) Electronic supplementary material The online version of this article (10.1007/s00268-020-05768-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- S Gasteiger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - F Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. .,Department of General, Vascular and Visceral Surgery, Salzkammergut Klinikum, Dr.-Wilhelm-Bock-Straße 1, 4840, Vöcklabruck, Austria.
| | - G Göbel
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Schoepfstrasse 41, 6020, Innsbruck, Austria
| | - E Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - B Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - M Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - S Sopper
- Department of Haematology and Oncology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - D Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - S Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.,Department of General, Vascular and Visceral Surgery, Salzkammergut Klinikum, Dr.-Wilhelm-Bock-Straße 1, 4840, Vöcklabruck, Austria
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Zhang W, Wei Z, Che X. Effect of polyglycolic acid mesh for prevention of pancreatic fistula after pancreatectomy: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e21456. [PMID: 32846759 PMCID: PMC7447380 DOI: 10.1097/md.0000000000021456] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Postoperative pancreatic fistula (POPF) is the most common and intractable complication after partial pancreatectomy, with an incidence of 13% to 64%. Polyglycolic acid (PGA) mesh is a new technique that is designed to prevent POPF, and its effect has been evaluated in several randomized controlled trials and some retrospective cohort studies. In this study, we systematically and comprehensively analyzed the efficacy of PGA mesh based on reported studies.We searched Medline, Embase, and Cochrane Library databases in English between January 2010 and October 2019. Analysis was performed by using Review Manger 5.3 software.Three RCTs and 8 nonrandomized studies were eligible with a total of 1598 patients including 884 PGA group patients and 714 control group patients. For pancreatoduodenectomy (PD), distal pancreatectomy (DP), and the 2 partial pancreatectomy (PD or DP), we found significant statistical differences in overall POPF (relative risk [RR] = 0.75, 95% confidence interval [CI] = 0.61-0.91, P = .004; RR = 0.74, 95% CI = 0.57-0.96, P = .02; RR = 0.76, 95% CI = 0.64-0.89, P = .0009, respectively) and clinical pancreatic fistula (PF) (RR = 0.5, 95% CI = 0.37-0.68, P < .00001; RR = 0.31, 95% CI = 0.21-0.46, P < .00001; RR = 0.41, 95% CI = 0.32-0.52, P < .00001, respectively) in favor of PGA. For partial pancreatectomy, significant statistical differences were found in overall complications (RR = 0.77, 95% CI: 0.67-0.88, P = .0002) and estimated blood loss (weighted mean difference [WMD] = -53.58; 95% CI: -101.20 to -5.97, P = .03) in favor of PGA. We did not find significant differences regarding operative time (WMD = -8.86; 95% CI: -27.59 to 9.87, P = .35) and hospital stay (WMD = -2.73; 95% CI: -7.53 to 2.06, P = .26).This meta-analysis shows the benefits of the PGA mesh technique regarding POPF, clinical PF, and postoperative complications. This still needs to be verified by more randomized control trials.
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Affiliation(s)
- Wei Zhang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
| | - Zhicheng Wei
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Xu Che
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
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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 2020; 43:3128-3137. [PMID: 31502003 DOI: 10.1007/s00268-019-05172-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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).
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Liu X, Pausch T, Probst P, Cui J, Wei J, Hackert T, Miao Y. Efficacy of Pasireotide for Prevention of Postoperative Pancreatic Fistula in Pancreatic Surgery: a Systematic Review and Meta-analysis. J Gastrointest Surg 2020; 24:1421-1429. [PMID: 32207077 DOI: 10.1007/s11605-019-04479-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 11/12/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Pasireotide was recently suggested for the prevention of postoperative pancreatic fistula (POPF) after pancreatic surgery. However, its efficacy remains to be controversially dicussed. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of pasireotide for preventing POPF after pancreatic surgery. METHOD A systematic literature search was conducted in PubMed, Web of Science, and The Cochrane Library to identify clinical studies investigating the efficacy of pasireotide after pancreatic surgery. The identified studies were critically appraised, and meta-analyses were then performed. The study was performed in accordance with PRISMA guidelines and was registered at the PROSPERO study database (CRD42018112334). RESULTS Four studies with a total of 919 patients were included: 418 with pasireotide treatment and 501 controls. Meta-analysis showed that pasireotide could reduce neither clinically relevant POPF rate (OR = 0.78; 95% CI, 0.49-1.24; P = 0.29) nor overall POPF rate (OR = 0.94; 95% CI, 0.60-1.48; P = 0.80) after pancreatic resections. There were no significant differences in delayed gastric emptying, mortality, and postoperative hospital stay after pancreatic surgery. However, pasireotide reduces readmission after pancreatic surgery (OR = 0.61; 95% CI, 0.44-0.85; P = 0.004). Subgroup analyses revealed that prophylactic use of pasireotide did not reduce the incidence of clinically relevant POPF after pancreaticoduodenectomy or distal pancreatectomy compared with the control. CONCLUSION Based on the available evidence, use of pasireotide may not reduce clinically relevant POPF as well as it may not improve postoperative course substantially after pancreatic surgery. Further investigator-initiated high-quality trials are needed.
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Affiliation(s)
- Xinchun Liu
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.,Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Department of Gastrointestinal Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Thomas Pausch
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Jiaqu Cui
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Jishu Wei
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Yi Miao
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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Zhou Q, Xia Y, Lei Z. The predictive value of procalcitonin for postoperative early pancreatic fistula. BMC Surg 2020; 20:90. [PMID: 32375732 PMCID: PMC7201992 DOI: 10.1186/s12893-020-00755-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 04/22/2020] [Indexed: 12/28/2022] Open
Abstract
Background To investigate the early prediction value of procalcitonin (PCT) in pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Method Retrospective analysis of clinical data of 67 patients undergoing pancreaticoduodenectomy (PD) and 19 patients undergoing distalpancreatectomy (DP) were performed in the Department of Hepatobiliary Surgery, Leshan People’s Hospital from January 2017 to December 2018. All patients were divided into POPF group and non-POPF group depending on the presence of pancreatic fistula. And fistulas were classified according to the ISGPF classification scheme. Plasma PCT levels, serum CRP concentration, and WBC counts were assessed preoperatively and on postoperative days (PODs) 1, 3, and 5. Statistical analyses were performed with statistical software. The ROC curve was used to analyze the efficacy of PCT and CRP in POPF prediction after surgery and determine their Cut-off value. Result There were no statistically significant differences identified in age, gender, BMI, diabetes, abdominal surgery history, preoperative laboratory data, operation time, intraoperative bleeding volume, tumor nature and medical expenses of PD patients between the two groups (P > 0.05). While the incidence of postoperative hyperglycemia, postoperative ICU rate and postoperative hospital stay were statistically significant (P < 0.05). The AUC for PCT diagnosis of pancreatic fistula 1 day after surgery was 0.77 (95% CI: 0.675 ~ 0.860). Compared with CRP [0.53 (95% CI: 0.420 ~ 0.639)] and WBC [0.60 (95% CI: 0.490 ~ 0.705)], the optimal cut-off value (cut-off) was 0.67 μg/L. At this time, the sensitivity and specificity of detecting pancreatic fistula were 73.68 and 76.12%, respectively. The results at 3 days after surgery were similar to those at 5 days after surgery. And DP patients had similar results as PD patients. Conclusion The PCT is valuable for early prediction of pancreatic fistula after Pancreaticoduodenectomy.
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Affiliation(s)
- Quanyu Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The People's Hospital of Leshan City, Leshan, Sichuan, 614000, People's Republic of China
| | - Yuxiao Xia
- Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, No 15 TaiPing St, Jiangyang District, Luzhou, 64600, Sichuan, People's Republic of China
| | - Zehua Lei
- Department of Hepatobiliary and Pancreatic Surgery, The People's Hospital of Leshan City, Leshan, Sichuan, 614000, People's Republic of China.
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Deng Y, He S, Cheng Y, Cheng N, Gong J, Gong J, Zeng Z, Zhao L. Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. Cochrane Database Syst Rev 2020; 3:CD009621. [PMID: 32157697 PMCID: PMC7064369 DOI: 10.1002/14651858.cd009621.pub4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants have been used in some centers to reduce postoperative pancreatic fistula. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2018. OBJECTIVES To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS We searched trial registers and the following biomedical databases: the Cochrane Library (2019, Issue 2), MEDLINE (1946 to 13 March2019), Embase (1980 to 11 March 2019), Science Citation Index Expanded (1900 to 13 March 2019), and Chinese Biomedical Literature Database (CBM) (1978 to 13 March 2019). SELECTION CRITERIA We included all randomised controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS We included 12 studies involving 1604 participants in the review. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included seven studies involving 860 participants: 428 were randomised to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence) or length of hospital stay (MD 0.99 days, 95% CI -1.83 to 3.82; 371 participants; two studies; very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included four studies involving 393 participants: 186 were randomised to the fibrin sealant group and 207 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (16.7% versus 11.7%; RR 1.14, 95% CI 0.28 to 4.69; 199 participants; two studies; very low-quality evidence). We are uncertain whether fibrin sealants reduce postoperative mortality (0.5% versus 2.4%; Peto OR 0.26, 95% CI 0.05 to 1.32; 393 participants; four studies; low-quality evidence) or length of hospital stay (MD 0.01 days, 95% CI -3.91 to 3.94; 323 participants; three studies; very low-quality evidence). There is probably little or no difference in overall postoperative morbidity (52.6% versus 50.3%; RR 1.04, 95% CI 0.87 to 1.24; 323 participants; three studies; moderate-quality evidence) between the groups. We are uncertain whether fibrin sealants reduce reoperation rate (5.2% versus 7.7%; RR 0.74, 95% CI 0.33 to 1.66; 323 participants; three studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two studies involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (median 16 to 17 days versus 17 days; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study (169 participants; low-quality evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.
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Affiliation(s)
- Yilei Deng
- The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatopancreatobiliary SurgeryNo. 1, Jianshe East RoadZhengzhouHenan ProvinceChina450000
| | - Sirong He
- Chongqing Medical UniversityDepartment of Immunology, College of Basic MedicineNo. 1 Yixue RoadChongqingChina450000
| | - Yao Cheng
- The Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Hepatobiliary SurgeryNo. 74, Lin Jiang Road, ChongqingChongqingChina400010
| | - Nansheng Cheng
- West China Hospital, Sichuan UniversityDepartment of Bile Duct SurgeryNo. 37, Guo Xue XiangChengduSichuanChina610041
| | - Jianping Gong
- The Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Hepatobiliary SurgeryNo. 74, Lin Jiang Road, ChongqingChongqingChina400010
| | - Junhua Gong
- First Affiliated Hospital of Kunming Medical UniversityOrgan Transplant CenterNo. 295, Xi Chang RoadKunmingYunnanChina650032
| | - Zhong Zeng
- First Affiliated Hospital of Kunming Medical UniversityOrgan Transplant CenterNo. 295, Xi Chang RoadKunmingYunnanChina650032
| | - Longshuan Zhao
- The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatopancreatobiliary SurgeryNo. 1, Jianshe East RoadZhengzhouHenan ProvinceChina450000
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Yamazaki S, Takayama T, Mitsuka Y, Yoshida N, Yoshida N, Shimamoto N, Higaki T. Feasibility of Hyaluronate Carboxymethylcellulose-Based Bioresorbable Membrane in Two-Staged Pancreatojejunostomy. World J Surg 2019; 44:902-909. [PMID: 31654202 DOI: 10.1007/s00268-019-05253-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Two-staged pancreatoduodenectomy with exteriorization of pancreatic juice is a safe procedure for high-risk patients. However, two-staged pancreatoduodenectomy requires complex re-laparotomy and adhesion removal. We analyzed whether using hyaluronate carboxymethylcellulose-based bioresorbable membrane (HCM) reduced the time required for the second operation and facilitated good fistula formation in two-staged pancreatoduodenectomy. METHODS Between April 2011 and December 2018, data were collected from 206 consecutive patients who underwent two-staged pancreatoduodenectomy. HCM has been used for all patients since 2015. Patients for whom HCM was used (HCM group; n = 61) were compared to historical controls (before 2015) without HCM (control group; n = 145) in terms of feasibility of the second operation (operation time, adhesion grade, and complications) and optimal granulation around the external tube at the second laparotomy. RESULTS The HCM group showed significantly shorter median operation time [105 min (30-228 min) vs. 151 min (30-331 min); p < 0.001] and smaller median blood loss [36 mL (8-118 mL) vs. 58 mL (12-355 mL); p < 0.001] for the second operation. Neither overall postoperative complication rate (p = 0.811) nor severe-grade complication rate (p = 0.857) differed significantly. Both groups showed good fistula formation, with no significant difference in rate of optimal fistula formation (HCM group, 95.1% vs. control, 95.9%; p = 0.867). CONCLUSION HCM placement significantly improved safety and duration for the second operation, while preserving good fistula formation.
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Affiliation(s)
- Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan.
| | - Yusuke Mitsuka
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
| | - Nao Yoshida
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
| | - Naoki Yoshida
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
| | - Naoaki Shimamoto
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashigh-ku, Tokyo, 173-8610, Japan
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Kawaida H, Kono H, Hosomura N, Amemiya H, Itakura J, Fujii H, Ichikawa D. Surgical techniques and postoperative management to prevent postoperative pancreatic fistula after pancreatic surgery. World J Gastroenterol 2019; 25:3722-3737. [PMID: 31391768 PMCID: PMC6676555 DOI: 10.3748/wjg.v25.i28.3722] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/20/2019] [Accepted: 06/26/2019] [Indexed: 02/06/2023] Open
Abstract
Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.
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Affiliation(s)
- Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hiroshi Kono
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Naohiro Hosomura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hidetake Amemiya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Jun Itakura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hideki Fujii
- Department of Surgery, Kofu Manicipal Hospital, Yamanashi 400-0832, Japan
| | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
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Surgical and local therapeutic concepts of oligometastatic pancreatic cancer in the era of effective chemotherapy. Eur Surg 2019. [DOI: 10.1007/s10353-019-0589-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Outcomes following pancreatic resections—results and challenges of an Austrian university hospital compared to nationwide data and international centres. Eur Surg 2019. [DOI: 10.1007/s10353-019-0585-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Fiorentini G, Tamburrino D, Belfiori G, Crippa S, Partelli S, Falconi M. Which is the best pancreatic anastomosis? MINERVA CHIR 2019; 74:241-252. [PMID: 30665292 DOI: 10.23736/s0026-4733.19.07997-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Postoperative pancreatic fistula is responsible for most of the complications following pancreaticoduodenectomy and several surgical techniques and strategies to prevent it have been suggested. None of these was ever proved to be the safest. Aim of this review is to present existing evidence on the best pancreatic anastomosis.
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Affiliation(s)
- Guido Fiorentini
- Division of Pancreatic Surgery, IRCCS San Raffaele Hospital, Milan, Italy
| | | | - Giulio Belfiori
- Division of Pancreatic Surgery, IRCCS San Raffaele Hospital, Milan, Italy
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Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group. Eur J Surg Oncol 2018; 45:198-206. [PMID: 30262324 DOI: 10.1016/j.ejso.2018.08.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 08/09/2018] [Accepted: 08/24/2018] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Pancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments. METHODS Retrospective, national cohort-study from 7 medium-/high-volume centres in Austria, coordinated under the auspices of the Austrian Society of Surgical Oncology (ASSO). RESULTS Two-hundred patients underwent resection for pNEN, 177 had non-functioning tumours and 31 showed stage 4 disease. Participating centres were responsible for 2/3 of pNEN resections in Austria within the last years. The mean rate of completeness of variables was 98.6%. Ninety-days mortality was 3.5%, overall rate of complications was 42.5%. Morbidity did not influence long-term survival. The 5-year overall-survival (OS) was 81.3%, 10-year-OS 52.5% and 5-year recurrence-free-survival (RFS) 69.8%. Recurrence was most common in the liver (68.1%). Four out of five patients with recurrence underwent further treatment, most commonly with medical therapy or chemotherapy. Multivariable analysis revealed grading (HR:2.7) and metastasis (HR:2.5) as significant factors for relapse. Tumours-size ≥2 cm (HR:5.9), age ≥60 years (HR:3.1), metastasis (HR:2.3) and grading (HR:2.0) were associated with OS. Tumours <2 cm showed 93.9% 10-year-OS, but 33% had G2/G3 grading, 12.5% positive lymph-nodes and 4.7% metastasis at diagnosis, each associated with significant worse survival. CONCLUSION Resection of pNENs in Austria is performed with internationally comparable safety. Analysed factors allow for risk-stratification in clinical treatment and future prospective trials. A watch-and-wait strategy purely based on tumour-size cannot be recommended.
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