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Seki Y, Ishizawa T, Watanabe G, Komatsu T, Nanjo A, Ueno T, Urano Y, Kawaguchi M, Nakagawa H, Hasegawa K. Identification of a pancreatic juice-specific fluorescent probe through 411 probes activated by aminopeptidases/proteases or phosphatases/phosphodiesterases. HPB (Oxford) 2025; 27:150-158. [PMID: 39632145 DOI: 10.1016/j.hpb.2024.10.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 09/30/2024] [Accepted: 10/26/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND This study is a retrospective review aimed to identify pancreatic juice-specific fluorescent probes to visualize pancreatic juice using a library of 381 aminopeptidase/protease-activatable fluorescent probes and 30 phosphatase/phosphodiesterase probes. In 2013, we developed a fluorescence imaging technique using a chymotrypsin probe to visualize pancreatic juice, linked to postoperative pancreatic fistula (POPF). This probe required addition of trypsin to convert pancreatic chymotrypsinogen to chymotrypsin. Recently we accessed libraries of enzyme-activatable fluorescent probes to find probes that facilitated target-specific imaging. METHODS Pancreatic juice and ascitic fluid samples were collected in eight patients undergoing pancreaticoduodenectomy. Reaction rates of pancreatic juice to background ascitic fluids were calculated for these 411 fluorescent probes. RESULTS Forty-four fluorescent probes were screened in terms of high reactivity with pancreatic juice. Only one candidate probe targeting ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) 1 was selected for a pancreatic juice-specific fluorescent probe. Inhibitor experiments and Western blotting supported the presence of ENPP1 in the pancreatic juice. CONCLUSION ENPP1-targeting fluorescent probe may have the potential to visualize pancreatic juice leakage during surgery. This finding may allow surgeons to suture leaking sites and decide the necessity of prophylactic abdominal drains; however, the role of ENPP1 in pancreatic juice remains to be clarified.
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Affiliation(s)
- Yusuke Seki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Department of Gastroenterological Surgery, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Takeaki Ishizawa
- Department of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Genki Watanabe
- Department of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Toru Komatsu
- Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Aika Nanjo
- Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Tasuku Ueno
- Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Yasuteru Urano
- Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Mitsuyasu Kawaguchi
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan
| | - Hidehiko Nakagawa
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
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Doussot B, Doussot A, Ayav A, Santucci N, Deguelte S, Sow AK, El Amrani M, Duvillard L, Piessen G, Girard E, Mabrut JY, Garnier J, Ortega-Deballon P, Fournel I, Facy O. Diagnostic Accuracy of Lipase as Early Predictor of Postoperative Pancreatic Fistula: Results from the LIPADRAIN study. ANNALS OF SURGERY OPEN 2024; 5:e492. [PMID: 39310332 PMCID: PMC11415086 DOI: 10.1097/as9.0000000000000492] [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: 07/26/2024] [Accepted: 08/07/2024] [Indexed: 09/25/2024] Open
Abstract
Objective To evaluate the diagnostic accuracy of drain fluid lipase as an early predictor of postoperative pancreatic fistula and establish the most appropriate day for their measure. Background Clinically relevant postoperative pancreatic fistula remains a potentially life-threatening complication after pancreatic surgery. Early detection strategies remain key to reduce both the incidence and the burden of pancreatic fistula. Methods The LIPAse DRAIN (LIPADRAIN) study is a multicenter, prospective diagnostic study conducted in 7 tertiary university hospitals. Drain fluid values to detect clinically relevant postoperative pancreatic fistula from postoperative day 1 to postoperative day 6 were evaluated using receiver operating characteristic curve analysis. A biomarker was considered to be relevant for clinical use if its area under the curve (AUC) was greater than 0.75. Results Of the 625 patients included in the analysis, clinically relevant postoperative pancreatic fistula occurred in 203 (32%) patients. On postoperative days 3 and 4, drain fluid lipase was a reliable biomarker to detect clinically relevant postoperative pancreatic fistula (AUC: 0.761; 95% confidence interval [CI]: 0.761-0.799 and AUC: 0.784; 95% CI: 0.743-0.821, respectively). On postoperative day 3, with a threshold of 299 units/L, drain fluid lipase yielded a negative predictive value of 51%, sensitivity of 78%, and specificity of 63% for the detection of clinically relevant postoperative pancreatic fistula. Conclusions In this multicenter prospective study, drain fluid lipase is a reliable biomarker at postoperative days 3 and 4 for the diagnosis of clinically relevant postoperative pancreatic fistula after pancreatic surgery and should be systematically measured on postoperative day 3.
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Affiliation(s)
- Béranger Doussot
- From the Department of Digestive and Surgical Oncology, University Hospital Dijon, Dijon, France
| | - Alexandre Doussot
- Department of Digestive Surgical Oncology, Liver Transplantation Unit, CHU Besancon, Besancon, France
| | - Ahmet Ayav
- Department of Hepatobiliary, Colorectal and Digestive Surgery, University of Nancy, CHU Nancy-Brabois, Nancy, France
| | - Nicolas Santucci
- From the Department of Digestive and Surgical Oncology, University Hospital Dijon, Dijon, France
| | - Sophie Deguelte
- Department of Endocrine, Digestive and Oncological Surgery, Robert-Debré University Hospital, Reims, France
| | - Amadou Khalilou Sow
- INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, Dijon, France
| | - Mehdi El Amrani
- Department of Digestive Surgery and Liver Transplantation, Claude Huriez University Hospital, Lille, France
| | - Laurence Duvillard
- Université de Bourgogne, INSERM Research Center U1231- PADYS team, Department of Biochemistry, University Hospital Dijon, Dijon, France
- Department of Biochemistry, University Hospital Dijon, Dijon, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Edouard Girard
- Colorectal Unit, Department of Surgery, Grenoble Alpes University Hospital, Grenoble, France
| | - Jean-Yves Mabrut
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hospital Croix Rousse, Lyon, France
| | - Jonathan Garnier
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France
| | - Pablo Ortega-Deballon
- From the Department of Digestive and Surgical Oncology, University Hospital Dijon, Dijon, France
| | - Isabelle Fournel
- INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, Dijon, France
| | - Olivier Facy
- From the Department of Digestive and Surgical Oncology, University Hospital Dijon, Dijon, France
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Verdeyen N, Gryspeerdt F, Abreu de Carvalho L, Dries P, Berrevoet F. A Comparison of Preoperative Predictive Scoring Systems for Postoperative Pancreatic Fistula after Pancreaticoduodenectomy Based on a Single-Center Analysis. J Clin Med 2024; 13:3286. [PMID: 38892998 PMCID: PMC11172640 DOI: 10.3390/jcm13113286] [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: 05/11/2024] [Revised: 05/26/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Background: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is associated with major postoperative morbidity and mortality. Several scoring systems have been described to stratify patients into risk groups according to the risk of POPF. The aim of this study was to compare scoring systems in patients who underwent a PD. Methods: A total of 196 patients undergoing PD from July 2019 to June 2022 were identified from a prospectively maintained database of the University Hospital Ghent. After performing a literature search, four validated, solely preoperative risk scores and the intraoperative Fistula Risk Score (FRS) were included in our analysis. Furthermore, we eliminated the variable blood loss (BL) from the FRS and created an additional score. Univariate and multivariate analyses were performed for all risk factors, followed by a ROC analysis for the six scoring systems. Results: All scores showed strong prognostic stratification for developing POPF (p < 0.001). FRS showed the best predictive accuracy in general (AUC 0.862). FRS without BL presented the best prognostic value of the scores that included solely preoperative variables (AUC 0.783). Soft pancreatic texture, male gender, and diameter of the Wirsung duct were independent prognostic factors on multivariate analysis. Conclusions: Although all predictive scoring systems stratify patients accurately by risk of POPF, preoperative risk stratification could improve clinical decision-making and implement preventive strategies for high-risk patients. Therefore, the preoperative use of the FRS without BL is a potential alternative.
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Affiliation(s)
- Naomi Verdeyen
- Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium;
| | - Filip Gryspeerdt
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (F.G.); (L.A.d.C.); (P.D.)
| | - Luìs Abreu de Carvalho
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (F.G.); (L.A.d.C.); (P.D.)
| | - Pieter Dries
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (F.G.); (L.A.d.C.); (P.D.)
| | - Frederik Berrevoet
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (F.G.); (L.A.d.C.); (P.D.)
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Rykina-Tameeva N, MacCulloch D, Hipperson L, Ulyannikova Y, Samra JS, Mittal A, Sahni S. Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis. Int J Surg 2023; 109:2486-2499. [PMID: 37216227 PMCID: PMC10442108 DOI: 10.1097/js9.0000000000000482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 05/08/2023] [Indexed: 05/24/2023]
Abstract
BACKGROUND Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis. METHODS Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies. RESULTS Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1. CONCLUSIONS The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.
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Affiliation(s)
- Nadya Rykina-Tameeva
- Faculty of Medicine and Health, University of Sydney
- Kolling Institute of Medical Research, University of Sydney, St Leonards
| | | | - Luke Hipperson
- Faculty of Medicine and Health, University of Sydney
- Kolling Institute of Medical Research, University of Sydney, St Leonards
| | | | - Jaswinder S. Samra
- Faculty of Medicine and Health, University of Sydney
- Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital
- Australian Pancreatic Centre, St Leonards
| | - Anubhav Mittal
- Faculty of Medicine and Health, University of Sydney
- Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital
- Australian Pancreatic Centre, St Leonards
- The University of Notre Dame Australia, Sydney, New South Wales, Australia
| | - Sumit Sahni
- Faculty of Medicine and Health, University of Sydney
- Kolling Institute of Medical Research, University of Sydney, St Leonards
- Australian Pancreatic Centre, St Leonards
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Rykina-Tameeva N, Samra JS, Sahni S, Mittal A. Drain fluid biomarkers for prediction and diagnosis of clinically relevant postoperative pancreatic fistula: A narrative review. World J Gastrointest Surg 2022; 14:1089-1106. [PMID: 36386401 PMCID: PMC9640330 DOI: 10.4240/wjgs.v14.i10.1089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 09/16/2022] [Accepted: 10/14/2022] [Indexed: 02/07/2023] Open
Abstract
Clinically relevant postoperative pancreatic fistula (CR-POPF) has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and diagnosis. The current diagnostic criteria for CR-POPF requires elevated drain fluid amylase to present alongside POPF-related complications including infection, haemorrhage and organ failure. These worrying sequelae necessitate earlier and easily obtainable biomarkers capable of reflecting evolving CR-POPF. Drain fluid has recently emerged as a promising source of biomarkers as it is derived from the pancreas and hence, capable of reflecting its postoperative condition. The present review aims to summarise the current knowledge of CR-POPF drain fluid biomarkers and identify gaps in the field to invigorate future research in this critical area of clinical need. These findings may provide robust diagnostic alternatives for CR-POPF and hence, to clarify their clinical utility require further reports detailing their diagnostic and/or predictive accuracy.
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Affiliation(s)
| | - Jaswinder S Samra
- Northern Clinical School, University of Sydney, St Leonards 2065, Australia
| | - Sumit Sahni
- Northern Clinical School, University of Sydney, St Leonards 2065, Australia
| | - Anubhav Mittal
- Northern Clinical School, University of Sydney, St Leonards 2065, Australia
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Tzedakis S, Sauvanet A, Schiavone R, Razafinimanana M, Cauchy F, Rouet J, Dousset B, Gaujoux S. What should we trust to define, predict and assess pancreatic fistula after pancreatectomy? Pancreatology 2020; 20:1779-1785. [PMID: 33077382 DOI: 10.1016/j.pan.2020.10.036] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 10/04/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The ISGPF postoperative pancreatic fistula (POPF) definition using amylase drain concentration is widely used. However, the interest of lipase drain concentration, daily drain output and absolute enzyme daily production (concentration x daily drain volume) have been poorly investigated. MATERIAL AND METHODS These predictive on postoperative day (POD) 1, 3, 5 and 7 were analyzed in a development cohort, and subsequently tested in an independent validation cohort. RESULTS Of the 227 patients of the development cohort, 17% developed a biochemical fistula and 34% a POPF (Grade B/C). Strong correlation was found between amylase/lipase drain concentration at all postoperative days (ρ = 0.90; p = 0.001). Amylase and lipase were both significantly higher in patients with a POPF (p < 0.001) presenting an equivalent under the ROC curve area (0.85 vs 0.84; p = 0.466). Combining POD1 and POD3 threefold enzyme cut-off value increased significantly POPF prediction sensibility (97.4% vs 77.8%) and NPV (97.1% vs 86.3%). These results were also confirmed in the validation cohort of 554 patients. Finally, absolute enzyme daily production and daily drain output were significantly higher in patients with a POPF (p < 0.001) but did not add clinical value when compared to drain enzyme concentration. CONCLUSION Lipase is as effective as amylase drain concentration to define POPF. Absolute enzyme daily production or daily drain output do not help to better predict clinically significant POPF occurrence and severity. Lipase and amylase should mainly be used for their negative predictive value to predict the absence of clinically significant POPF and could allow early drain removal and hospital discharge.
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Affiliation(s)
- Stylianos Tzedakis
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Alain Sauvanet
- Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Hospital Beaujon, APHP, Clichy, France; University of Paris, Paris, France
| | - Roberto Schiavone
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Meva Razafinimanana
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - François Cauchy
- Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Hospital Beaujon, APHP, Clichy, France; University of Paris, Paris, France
| | - Jérémy Rouet
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France; Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Hospital Beaujon, APHP, Clichy, France
| | - Bertrand Dousset
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France; University of Paris, Paris, France
| | - Sébastien Gaujoux
- Department of Digestive, Hepato-biliary and Endocrine Surgery, La Pitié-Salpétrière Hospital, APHP, Paris, France; Médecine Sorbonne Université, Paris, France.
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Smits FJ, Molenaar IQ, Besselink MG, Borel Rinkes IHM, van Eijck CHJ, Busch OR, van Santvoort HC. Early recognition of clinically relevant postoperative pancreatic fistula: a systematic review. HPB (Oxford) 2020; 22:1-11. [PMID: 31445782 DOI: 10.1016/j.hpb.2019.07.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 06/14/2019] [Accepted: 07/13/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically evaluate the accuracy of postoperative clinical, biochemical and radiologic variables for early recognition of clinically relevant postoperative pancreatic fistula. METHODS A systematic literature search was performed up to August 2018. Clinical studies reporting on the association between postoperative variables and clinically relevant postoperative pancreatic fistula were included. Variables were stratified: early prediction (postoperative day 1-2) versus early diagnosis (day 3) and had to be reported in 2 cohorts. RESULTS Overall, 37 included studies reported on 17 different diagnostic variables after 8701 pancreatic resections. Clinically relevant postoperative pancreatic fistula occurred in 1532/8701 patients (18%). Early prediction variables included elevated serum and drain amylase (day 1). Identified variables for early diagnosis were: non-serous drain efflux (day 3); positive drain culture (day 3); elevated temperature (any day); elevated C-Reactive Protein (CRP; day 4); elevated white blood cell count (day 4) and peripancreatic collections on computed tomography (CT; day 5-10). CONCLUSION This review provides a comprehensive overview of postoperative variables associated with clinically relevant pancreatic fistula. Incorporation of variables in future algorithms could potentially mitigate the clinical impact of postoperative pancreatic fistula.
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Affiliation(s)
- F Jasmijn Smits
- Dept. of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands
| | - I Quintus Molenaar
- Dept. of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands; Dept. of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands
| | - Marc G Besselink
- Dept. of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
| | - Inne H M Borel Rinkes
- Dept. of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands
| | - Casper H J van Eijck
- Dept. of Surgery, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands
| | - Olivier R Busch
- Dept. of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
| | - Hjalmar C van Santvoort
- Dept. of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands; Dept. of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands.
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Müssle B, Oehme F, Schade S, Sommer M, Bogner A, Hempel S, Pochhammer J, Kahlert C, Distler M, Weitz J, Welsch T. Drain Amylase or Lipase for the Detection of POPF-Adding Evidence to an Ongoing Discussion. J Clin Med 2019; 9:jcm9010007. [PMID: 31861508 PMCID: PMC7019284 DOI: 10.3390/jcm9010007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/11/2019] [Accepted: 12/16/2019] [Indexed: 01/08/2023] Open
Abstract
Objectives: A postoperative pancreatic fistula (POPF) is defined as a threefold increase in the amylase concentration in abdominal drains on or after the third postoperative day (POD). However, additional lipase fluid analysis is widely used despite lacking evidence. In this study, drain amylase and lipase levels were compared regarding their value in detecting POPF. Methods: We conducted a retrospective study including all patients who underwent pancreatic resections at our center between 2005 and 2016. Drain fluid analysis was performed from day 2 to 5. Results: 990 patients were included in the analysis. Overall, 333 (34%) patients developed a POPF. The median amylase and lipase concentrations at POD 3 in cases with POPF were 11.55 µmol/(s·L) (≈13 ×-fold increase) and 39 µmol/(s·L) (≈39 ×-fold increase), respectively. Seven patients with subsequent POPF (2%) were missed with amylase analysis on POD 3, but detected using 3-fold lipase analysis. The false-positive rate of lipase was 51/424 = 12%. A cutoff lipase value at POD 3 of > 4.88 yielded a specificity of 94% and a sensitivity of 89% for development of a POPF. Increased body mass index turned out as risk factor for the development of POPF in a multivariable model. Conclusions: Threefold-elevated lipase concentration may be used as an indicator of a POPF. However, the additional detection of POPF using simultaneous lipase analysis is marginal. Therefore, assessment of lipase concentration does not provide added clinical value and only results in extra costs.
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Affiliation(s)
- Benjamin Müssle
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Florian Oehme
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Stephanie Schade
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Marian Sommer
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Andreas Bogner
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Sebastian Hempel
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Julius Pochhammer
- Department of General, Visceral, Thoracic, Transplant, and Pediatric Surgery, University Hospital Schleswig-Holstein, 24105 Kiel, Germany;
| | - Christoph Kahlert
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, 01307 TU Dresden, Germany; (B.M.); (F.O.); (S.S.); (M.S.); (A.B.); (S.H.); (C.K.); (M.D.); (J.W.)
- Correspondence: ; Tel.: +49-(0)351-458-18283
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Roy M, Ban EJ, Mohandas S, Mownah O, Banerjee A, Kocher H, Bhattacharya S, Hutchins R. Re: Comparison of lipase and amylase for diagnosing post-operative pancreatic fistulae. ANZ J Surg 2018; 88:1213-1214. [DOI: 10.1111/ans.14890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 08/30/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Mayank Roy
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Ee Jun Ban
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Shailesh Mohandas
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Omar Mownah
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Abhirup Banerjee
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Hemant Kocher
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Satya Bhattacharya
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
| | - Robert Hutchins
- Barts and the London HPB Centre; The Royal London Hospital, Barts Health NHS Trust; London UK
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