Editorial Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2024; 30(9): 1005-1010
Published online Mar 7, 2024. doi: 10.3748/wjg.v30.i9.1005
Early prediction and prevention of infected pancreatic necrosis
Cheng Lv, Zi-Xiong Zhang, Lu Ke, Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, Jiangsu Province, China
Lu Ke, Research Institute of Critical Care Medicine and Emergency Rescue, Nanjing University, Nanjing 210000, Jiangsu Province, China
ORCID number: Lu Ke (0000-0001-8093-5073).
Author contributions: Lv C, Zhang ZX, and Ke L designed the research study; Lv C and Zhang ZX searched the literature and wrote the original manuscript; Ke L reviewed the manuscript and supervised the whole work; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lu Ke, PhD, Associate Professor, Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 305 Zhongshan Road East, Nanjing 210000, Jiangsu Province, China. ctgkelu@nju.edu.cn
Received: December 18, 2023
Peer-review started: December 18, 2023
First decision: December 28, 2023
Revised: January 2, 2024
Accepted: February 6, 2024
Article in press: February 6, 2024
Published online: March 7, 2024

Abstract

Approximately 20%-30% of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis (IPN), a highly morbid and potentially lethal complication. Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes. In the past two decades, several markers and predictive tools have been proposed and evaluated for this purpose. Conventional biomarkers like C-reactive protein, procalcitonin, lymphocyte count, interleukin-6, and interleukin-8, and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN. On the other hand, scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested, and the results showed that they may provide better accuracy. For early prevention of IPN, several new therapies were tested, including early enteral nutrition, antibiotics, probiotics, immune enhancement, etc., but the results varied. Taken together, several evidence-supported predictive markers and scoring systems are readily available for predicting IPN. However, effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition. In this editorial, we summarize evidence concerning early prediction and prevention of IPN, providing insights into future practice and study design. A more homogeneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN, thereby achieving individualized treatment.

Key Words: Acute pancreatitis, Infected pancreatic necrosis, Biomarker, Scoring system, Nutrition therapy, Selective digestive decontamination, Probiotics, Antibiotics, Immune enhancement therapy

Core Tip: Several evidence-supported predictive markers and scoring systems are readily available for predicting infected pancreatic necrosis (IPN). However, effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition. In future research and practice, a more homogeneous patient population should be targeted with reliable risk-stratification tools since such a strategy may help find the effective treatment to reduce the risk of IPN, thereby achieving individualized treatment.



INTRODUCTION

Acute pancreatitis (AP) is one of the most common gastrointestinal illnesses worldwide[1]. The majority of AP cases are mild and self-limited, and such patients are discharged without complications. However, approximately 20% of AP patients develop a complex, prolonged clinical course characterized by pancreatic necrosis, especially when infected pancreatic necrosis (IPN) occurs[2,3]. Therefore, it is of clinical value to identify patients at high risk of IPN in the early phase of AP and provide appropriate preventive measures to improve their clinical outcomes.

In the past two decades, several new predictors and predictive tools have been proposed and evaluated, and several new therapies have been tested in trials to prevent IPN. In this editorial, we summarize evidence concerning the early prediction and prevention of IPN (Figure 1), providing insights into future practice and study design.

Figure 1
Figure 1 Summary of evidence concerning early prediction and prevention of infected pancreatic necrosis. CRP: C-reactive protein; PCT: Procalcitonin; IL-6 and 8: Interleukins-6 and -8; Ang-2: Angiopoietin-2; ALC: Absolute lymphocyte count; APACHE II: Acute Physiology and Chronic Health Evaluation II; SIRS: systemic inflammatory response syndrome; PASS: Pancreatitis Activity Scoring System; mPASS: Modified Pancreatitis Activity Scoring System; EN: Enteral nutrition; PN: Parenteral nutrition; Tα1: Thymosin alpha 1.
EARLY PREDICTION OF IPN
Biomarkers

Many classical biomarkers indicating the inflammation and severity of AP, including C-reactive protein (CRP)[3,4], procalcitonin (PCT)[5], interleukins-6 and -8 (IL-6 and IL-8)[6,7], had showed significant association with IPN in individual studies and meta-analysis[8]. Moreover, in a substudy of the PROPATRIA trial, Buddingh et al[9] discovered that plasma angiopoietin-2 (Ang-2), which plays an important role in the autocrine regulation of vascular stability and permeability, was a better biomarker than conventional predictors such as CRP, PCT, and the Imrie score with a cut-off value at 4.51 mg/L.

The relationship between immunosuppression and the development of IPN has also been recognized in the past[10], and biomarkers such as interferon-γ[11] and monocyte surface expression of HLA-DR antigens[12,13] have been tested to reflect the severity of immunosuppression. However, most of these markers are not readily available in hospitals. Through a post-hoc analysis of the TRACE trial[14], Cai et al[15] found that absolute lymphocyte count (ALC), a more readily available clinical measure, can predict the occurrence of IPN. Since ALC is a routine laboratory measurement, it might be of wider clinical use in practice.

Scoring systems

Several clinical scoring systems have been shown to predict IPN with adequate accuracy. The first is the Acute Physiology and Chronic Health Evaluation (APACHE) II. An APACH II score of more than 8 at admission was found to be a risk factor for IPN in patients with severe AP (SAP)[8,16]. Systemic Inflammatory Response Syndrome (SIRS) score was another option since persistent inflammation is involved in the development of IPN[16,17]. An observational study showed that longer SIRS duration was significantly associated with a higher incidence of IPN[18].

The Pancreatitis Activity Scoring System (PASS), which is an AP-specific score to reflect the disease severity, was tested in the prediction of IPN. In a retrospective study conducted by Ke et al[19], the predictive accuracy of the PASS score at admission was better than the APACHE II score in predicting IPN. However, considering the dominating weight assigned to opioid usage in the PASS, Paragomi et al[20] modified the original PASS score by removing or partly reducing the weight of opioid usage (mPASS 1-4). The mPASS could predict SAP with reasonable accuracy and differentiate between patients with different early trajectories in patients with different severities. For the prediction of IPN, Mao et al[21] found that the mPASS-4 model outperformed the conventional indices in predicting IPN, thereby increasing the likelihood of clinical usage.

EARLY PREVENTION OF IPN

In the past few decades, multiple attempts have been made to reduce the incidence of IPN, including nutrition therapy, selective digestive decontamination (SDD), antibiotic therapy, and immune enhancement. Unfortunately, most of the studies have not come to a positive conclusion.

Nutrition therapy

Two different randomized controlled trials[22,23] conducted in patients with SAP demonstrated that early total enteral nutrition, compared with total parenteral nutrition, could reduce the incidence of IPN, thereby reducing organ failure and mortality. On the one hand, the lack of enteral feeding results in atrophy of the gastrointestinal mucosa, bacterial overgrowth, and increased intestinal permeability[24]. On the other hand, parenteral nutrition (enteric starvation) was associated with rapid and severe atrophy of lymphoid tissue associated with the gut[25-27]. As a result, early enteral nutrition may alleviate the translocation of bacteria or bacterial products into the circulation[28-31].

SDD

In the 1980s, investigations into the source of infection in SAP patients found that Gram-negative aerobic bacteria originating from the digestive tract are predominantly isolated from IPN samples[32,33]. Accordingly, SDD has gained broad interest among the research community. The results of a more recent randomized trial[34] with a relatively small sample size of 102 SAP patients showed that SDD could significantly reduce the incidence of IPN, which was associated with improved morbidity and mortality. However, these results have not been confirmed by a large, multicenter trial, and therefore, SDD has not become a standard of care in current guidelines[35].

Probiotics

In experimental and small clinical studies, certain strains of probiotic bacteria might prevent infectious complications by reducing small-bowel bacterial overgrowth, restoring gastrointestinal barrier function, and modulating the immune system[36,37]. To confirm the clinical significance of probiotics in SAP patients, Besselink et al[38] conducted a large, randomized, double-blind, controlled trial testing the effect of probiotic therapy on the incidence of infectious complications. Unfortunately, the results showed no beneficial effect of probiotic prophylaxis on multiple infectious complications. On the contrary, mortality in the probiotics group was about twice as high as in the placebo group, which might be attributed to an increased incidence of bowel ischemia. The administration of probiotic bacteria daily as an adjunct to enteral nutrition might increase local oxygen demand, with a combined deleterious effect on the already compromised blood flow. Another possible explanation could be that the presence of probiotics caused local inflammation at the mucosal level. Experimental studies have shown that gut epithelial cells under metabolic stress react to commensal bacteria with an inflammatory response[39]. Recently, in addition to Gram-negative bacteria, infections associated with Gram-positive bacteria and yeasts were observed with an increasing incidence[40-42]. Therefore, research interests in the source of bacteria in IPN patients have been raised again, and the corresponding preventive measures need to be further studied.

Antibiotics

Systemic antibiotic prophylaxis has long been considered effective in preventing secondary infection in AP[43]. The results from a randomized controlled trial testing prophylactic meropenem suggest that although early antibiotic treatment might reduce the occurrence of septic complications and improve the prognosis of AP, it does not prevent the occurrence of IPN[44]. However, another randomized, double-blind trial conducted in patients with sterile necrotizing pancreatitis demonstrated similar rates of infection, operation, and death between the groups receiving meropenem or placebo[45]. In addition, imipenem-cilastatin was also tested in patients with ANP. However, it did not reduce the incidence of IPN and increased the risk of fungal infections[46].

In summary, current evidence does not support the use of prophylactic antibiotics in patients with necrotizing pancreatitis since it is ineffective in reducing IPN and may be associated with potential risks.

Immune enhancement therapy

Given that there is evidence of immunosuppression in the early phase of SAP and its association with infectious complications[10,47-49], the Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG) conducted serial trials to test the effects of immune enhancement by subcutaneous injection of thymosin alpha 1 (Tα1) on the incidence of IPN[14]. In the pilot trial, it was found that the 28-d positive blood culture rate was almost half in the thymosin α1 group than in the control group (16.6% vs 41.7%, P = 0.012), and the rate of IPN decreased from 29.4% to 8.3% (P = 0.036) after the treatment of thymosin α1. However, the phase III confirmatory trial found that the immune-enhancing Tα1 treatment did not significantly reduce the incidence of IPN compared with placebo in patients with predicted severe ANP. This was followed by a post-hoc analysis of the trial[50], which found that patients with predicted severe ANP and no lymphopenia (baseline ALC ≥ 0.8 × 109/L) may benefit from Tα1. However, due to the post-hoc design, new trials are needed to confirm the findings before any formal recommendation can be made.

CONCLUSION

In conclusion, several evidence-supported predictive markers and scoring systems are readily available for predicting IPN. However, effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition. In future research, a more homogeneous group of patients should be selected with reliable risk-stratification tools since such a strategy may help find the effective treatment to reduce the risk of IPN, thereby achieving individualized treatment.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Mohapatra S, India S-Editor: Chen YL L-Editor: Wang TQ P-Editor: Zheng XM

References
1.  Xiao AY, Tan ML, Wu LM, Asrani VM, Windsor JA, Yadav D, Petrov MS. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016;1:45-55.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 271]  [Cited by in F6Publishing: 366]  [Article Influence: 45.8]  [Reference Citation Analysis (0)]
2.  Forsmark CE, Vege SS, Wilcox CM. Acute Pancreatitis. N Engl J Med. 2016;375:1972-1981.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 410]  [Cited by in F6Publishing: 437]  [Article Influence: 54.6]  [Reference Citation Analysis (0)]
3.  Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102-111.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4134]  [Cited by in F6Publishing: 3687]  [Article Influence: 335.2]  [Reference Citation Analysis (38)]
4.  Gomatos IP, Xiaodong X, Ghaneh P, Halloran C, Raraty M, Lane B, Sutton R, Neoptolemos JP. Prognostic markers in acute pancreatitis. Expert Rev Mol Diagn. 2014;14:333-346.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 35]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
5.  Rau BM, Kemppainen EA, Gumbs AA, Büchler MW, Wegscheider K, Bassi C, Puolakkainen PA, Beger HG. Early assessment of pancreatic infections and overall prognosis in severe acute pancreatitis by procalcitonin (PCT): a prospective international multicenter study. Ann Surg. 2007;245:745-754.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 162]  [Cited by in F6Publishing: 139]  [Article Influence: 8.2]  [Reference Citation Analysis (0)]
6.  Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut. 1997;41:832-840.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 230]  [Cited by in F6Publishing: 253]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
7.  Ji L, Lv JC, Song ZF, Jiang MT, Li L, Sun B. Risk factors of infected pancreatic necrosis secondary to severe acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2016;15:428-433.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 17]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
8.  Li W, Ou L, Fu Y, Chen Y, Yin Q, Song H. Risk factors for concomitant infectious pancreatic necrosis in patients with severe acute pancreatitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2022;46:101901.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Reference Citation Analysis (0)]
9.  Buddingh KT, Koudstaal LG, van Santvoort HC, Besselink MG, Timmer R, Rosman C, van Goor H, Nijmeijer RM, Gooszen H, Leuvenink HG, Ploeg RJ, Nieuwenhuijs VB. Early angiopoietin-2 levels after onset predict the advent of severe pancreatitis, multiple organ failure, and infectious complications in patients with acute pancreatitis. J Am Coll Surg. 2014;218:26-32.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 25]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
10.  Ueda T, Takeyama Y, Yasuda T, Shinzeki M, Sawa H, Nakajima T, Ajiki T, Fujino Y, Suzuki Y, Kuroda Y. Immunosuppression in patients with severe acute pancreatitis. J Gastroenterol. 2006;41:779-784.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 46]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
11.  Gardiner BJ, Lee SJ, Cristiano Y, Levvey BJ, Sullivan LC, Snell GI, Peleg AY, Westall GP. Evaluation of Quantiferon®-Monitor as a biomarker of immunosuppression and predictor of infection in lung transplant recipients. Transpl Infect Dis. 2021;23:e13550.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 8]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
12.  Minkov G, Dimitrov E, Yovtchev Y, Enchev E, Lokova R, Halacheva K. Prognostic value of peripheral blood CD14+HLA-DR+ monocytes in patients with acute pancreatitis. J Immunoassay Immunochem. 2021;42:478-492.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
13.  Chéron A, Monneret G, Landelle C, Floccard B, Allaouchiche B. [Low monocytic HLA-DR expression and risk of secondary infection]. Ann Fr Anesth Reanim. 2010;29:368-376.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 12]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
14.  Ke L, Zhou J, Mao W, Chen T, Zhu Y, Pan X, Mei H, Singh V, Buxbaum J, Doig G, He C, Gu W, Lu W, Tu S, Ni H, Zhang G, Zhao X, Sun J, Chen W, Song J, Shao M, Tu J, Xia L, He W, Zhu Q, Li K, Yao H, Wu J, Fu L, Jiang W, Zhang H, Lin J, Li B, Tong Z, Windsor J, Liu Y, Li W; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial. Intensive Care Med. 2022;48:899-909.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 15]  [Article Influence: 7.5]  [Reference Citation Analysis (0)]
15.  Cai T, Mao W, Liu M, Zhou J, Wang X, Liu Y, Lv G, Ke L, Zhang Y. Early mean absolute lymphocyte count in acute necrotizing pancreatitis is associated with infected pancreatic necrosis. Int Immunopharmacol. 2023;117:109883.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
16.  Pando E, Alberti P, Hidalgo J, Vidal L, Dopazo C, Caralt M, Blanco L, Gómez-Gavara C, Bilbao I, Balsells J, Charco R. The role of extra-pancreatic infections in the prediction of severity and local complications in acute pancreatitis. Pancreatology. 2018;18:486-493.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 18]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
17.  Zerem E. Treatment of severe acute pancreatitis and its complications. World J Gastroenterol. 2014;20:13879-13892.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 185]  [Cited by in F6Publishing: 190]  [Article Influence: 19.0]  [Reference Citation Analysis (5)]
18.  Tan C, Yang L, Shi F, Hu J, Zhang X, Wang Y, Deng Z, Li J, Yuan H, Shi T, Li C, Xiao Y, Peng Y, Xu W, Huang Y. Early Systemic Inflammatory Response Syndrome Duration Predicts Infected Pancreatic Necrosis. J Gastrointest Surg. 2020;24:590-597.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 11]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
19.  Ke L, Mao W, Li X, Zhou J, Li G, Ye B, Tong Z, Li W. The Pancreatitis Activity Scoring System in Predicting Infection of Pancreatic Necrosis. Am J Gastroenterol. 2018;113:1393-1394.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 5]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
20.  Paragomi P, Hinton A, Pothoulakis I, Talukdar R, Kochhar R, Goenka MK, Gulla A, Gonzalez JA, Singh VK, Bogado MF, Stevens T, Barbu ST, Nawaz H, Gutierrez SC, Zarnescu N, Archibugi L, Easler JJ, Triantafyllou K, Peláez-Luna M, Thakkar S, Ocampo C, Enrique de-Madaria, Cote GA, Lee PJ, Krishna S, Lara LF, Han S, Wu BU, Papachristou GI. The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study. Clin Gastroenterol Hepatol. 2022;20:1334-1342.e4.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 9]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
21.  Mao W, Li K, Zhou J, Chen M, Ye B, Li G, Singh V, Buxbaum J, Fu X, Tong Z, Liu Y, Windsor J, Li W, Ke L; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Prediction of infected pancreatic necrosis in acute necrotizing pancreatitis by the modified pancreatitis activity scoring system. United European Gastroenterol J. 2023;11:69-78.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
22.  Petrov MS, Kukosh MV, Emelyanov NV. A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg. 2006;23:336-44; discussion 344.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 160]  [Cited by in F6Publishing: 154]  [Article Influence: 8.6]  [Reference Citation Analysis (0)]
23.  Wu XM, Ji KQ, Wang HY, Li GF, Zang B, Chen WM. Total enteral nutrition in prevention of pancreatic necrotic infection in severe acute pancreatitis. Pancreas. 2010;39:248-251.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 54]  [Cited by in F6Publishing: 52]  [Article Influence: 3.7]  [Reference Citation Analysis (1)]
24.  Li P, Jian JN, Chen RL. Effect of Early Enteral Nutrition on Serum Inflammatory Factors and Intestinal Mucosal Permeability in Patients with Severe Acute Pancreatitis. Turk J Gastroenterol. 2021;32:907-912.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
25.  King BK, Li J, Kudsk KA. A temporal study of TPN-induced changes in gut-associated lymphoid tissue and mucosal immunity. Arch Surg. 1997;132:1303-1309.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 96]  [Article Influence: 3.6]  [Reference Citation Analysis (0)]
26.  Janu P, Li J, Renegar KB, Kudsk KA. Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition. Ann Surg. 1997;225:707-15; discussion 715.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 68]  [Cited by in F6Publishing: 73]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
27.  Kudsk KA, Li J, Renegar KB. Loss of upper respiratory tract immunity with parenteral feeding. Ann Surg. 1996;223:629-35; discussion 635.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 156]  [Cited by in F6Publishing: 164]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
28.  Hadfield RJ, Sinclair DG, Houldsworth PE, Evans TW. Effects of enteral and parenteral nutrition on gut mucosal permeability in the critically ill. Am J Respir Crit Care Med. 1995;152:1545-1548.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 213]  [Cited by in F6Publishing: 226]  [Article Influence: 7.8]  [Reference Citation Analysis (0)]
29.  Nakasaki H, Mitomi T, Tajima T, Ohnishi N, Fujii K. Gut bacterial translocation during total parenteral nutrition in experimental rats and its countermeasure. Am J Surg. 1998;175:38-43.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 30]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
30.  Shou J, Lappin J, Minnard EA, Daly JM. Total parenteral nutrition, bacterial translocation, and host immune function. Am J Surg. 1994;167:145-150.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 79]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
31.  Qiu JG, Delany HM, Teh EL, Freundlich L, Gliedman ML, Steinberg JJ, Chang CJ, Levenson SM. Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation. Nutrition. 1997;13:431-437.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 20]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
32.  Beger HG, Bittner R, Block S, Büchler M. Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology. 1986;91:433-438.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 626]  [Cited by in F6Publishing: 656]  [Article Influence: 17.3]  [Reference Citation Analysis (0)]
33.  Runkel NS, Moody FG, Smith GS, Rodriguez LF, LaRocco MT, Miller TA. The role of the gut in the development of sepsis in acute pancreatitis. J Surg Res. 1991;51:18-23.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 142]  [Cited by in F6Publishing: 150]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
34.  Luiten EJ, Hop WC, Lange JF, Bruining HA. Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg. 1995;222:57-65.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 295]  [Cited by in F6Publishing: 323]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
35.  Baron TH, DiMaio CJ, Wang AY, Morgan KA. American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis. Gastroenterology. 2020;158:67-75.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 240]  [Cited by in F6Publishing: 296]  [Article Influence: 74.0]  [Reference Citation Analysis (2)]
36.  Bengmark S. Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut. 1998;42:2-7.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 285]  [Cited by in F6Publishing: 296]  [Article Influence: 11.4]  [Reference Citation Analysis (0)]
37.  Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361:512-519.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2194]  [Cited by in F6Publishing: 1995]  [Article Influence: 95.0]  [Reference Citation Analysis (0)]
38.  Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG; Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:651-659.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 944]  [Cited by in F6Publishing: 820]  [Article Influence: 51.3]  [Reference Citation Analysis (0)]
39.  Okumura R, Takeda K. Roles of intestinal epithelial cells in the maintenance of gut homeostasis. Exp Mol Med. 2017;49:e338.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 280]  [Cited by in F6Publishing: 383]  [Article Influence: 54.7]  [Reference Citation Analysis (0)]
40.  Isenmann R, Schwarz M, Rau B, Trautmann M, Schober W, Beger HG. Characteristics of infection with Candida species in patients with necrotizing pancreatitis. World J Surg. 2002;26:372-376.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 95]  [Cited by in F6Publishing: 103]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
41.  Grewe M, Tsiotos GG, Luque de-Leon E, Sarr MG. Fungal infection in acute necrotizing pancreatitis. J Am Coll Surg. 1999;188:408-414.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 88]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
42.  Hoerauf A, Hammer S, Müller-Myhsok B, Rupprecht H. Intra-abdominal Candida infection during acute necrotizing pancreatitis has a high prevalence and is associated with increased mortality. Crit Care Med. 1998;26:2010-2015.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 87]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
43.  Working Party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland;  Pancreatic Society of Great Britain and Ireland;  Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut. 2005;54 Suppl 3:iii1-iii9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 184]  [Cited by in F6Publishing: 351]  [Article Influence: 18.5]  [Reference Citation Analysis (0)]
44.  Manes G, Uomo I, Menchise A, Rabitti PG, Ferrara EC, Uomo G. Timing of antibiotic prophylaxis in acute pancreatitis: a controlled randomized study with meropenem. Am J Gastroenterol. 2006;101:1348-1353.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 59]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
45.  Dellinger EP, Tellado JM, Soto NE, Ashley SW, Barie PS, Dugernier T, Imrie CW, Johnson CD, Knaebel HP, Laterre PF, Maravi-Poma E, Kissler JJ, Sanchez-Garcia M, Utzolino S. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg. 2007;245:674-683.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 251]  [Cited by in F6Publishing: 204]  [Article Influence: 12.0]  [Reference Citation Analysis (0)]
46.  Maraví-Poma E, Gener J, Alvarez-Lerma F, Olaechea P, Blanco A, Domínguez-Muñoz JE; Spanish Group for the Study of Septic Complications in Severe Acute Pancreatitis. Early antibiotic treatment (prophylaxis) of septic complications in severe acute necrotizing pancreatitis: a prospective, randomized, multicenter study comparing two regimens with imipenem-cilastatin. Intensive Care Med. 2003;29:1974-1980.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 51]  [Article Influence: 2.4]  [Reference Citation Analysis (0)]
47.  Yu WK, Li WQ, Li N, Li JS. Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase of acute pancreatitis. Pancreatology. 2004;4:233-243.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 30]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
48.  Pan T, Zhou T, Li L, Liu Z, Chen Y, Mao E, Li M, Qu H, Liu J. Monocyte programmed death ligand-1 expression is an early marker for predicting infectious complications in acute pancreatitis. Crit Care. 2017;21:186.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 27]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
49.  Li J, Yang WJ, Huang LM, Tang CW. Immunomodulatory therapies for acute pancreatitis. World J Gastroenterol. 2014;20:16935-16947.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 24]  [Cited by in F6Publishing: 23]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
50.  Ke L, Mao W, Shao F, Zhou J, Xu M, Chen T, Liu Y, Tong Z, Windsor J, Ma P, Li W; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial. EClinicalMedicine. 2023;58:101915.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]