Peritoneal Cytokine Release after Elective Gastrointestinal Surgery and Postoperative Complications

doi:10.1016/S0002-9610(98)00010-5

The American Journal of Surgery

Volume 175, Issue 4, April 1998, Pages 311-316

https://doi.org/10.1016/S0002-9610(98)00010-5 Get rights and content

Abstract

Background: Laparotomy is known to give rise to systemic and local cytokine release. In the present study we investigated the course of the peritoneal response of tumor necrosis factor α (TNFα), interleukin (IL)-6, and IL-10 after elective gastrointestinal surgery and studied the differences in local cytokine response in patients developing postoperative complications.

Methods: Twelve consecutive patients underwent pancreatoduodenectomy (n = 9) or biliary and gastric bypass (n = 3) for pancreatic carcinoma. Sampling (TNFα, IL-6, IL-10) of fluid from abdominal drains was performed at return to the recovery unit (T=0), and at 3, 6, 18, 30, 42, 54, 66, 78 hours. Systemic sampling was performed at T=0, 3, 6, 18, 42, 66 hours. Postoperative cytokine response in patients with and without postoperative complications was compared.

Results: In patients without postoperative complications, peritoneal TNFα and IL-10 levels decreased in time (P = 0.07 and P = 0.01, respectively), whereas IL-6 did not change significantly during sampling (P = 0.28). Systemic IL-6 and IL-10 levels decreased 10-fold within 66 hours (IL-6, P = 0.04; IL-10, P = 0.06). Four patients experienced postoperative complications. All 4 patients with complications showed a second rise in peritoneal TNFα levels preceding the complication. All 4 patients had positive bacterial drain cultures from the abdominal drain, following the TNFα rise.

Conclusions: After elective abdominal surgery, cytokines are released into the abdominal cavity. Intra-abdominal complications are accompanied or preceded by a peritoneal TNFα rise. In patients after elective gastrointestinal surgery, monitoring of peritoneal TNFα might be helpful in the early detection of severe intra-abdominal complications.

Section snippets

Patients

From July 1996 to September 1996, 12 consecutive patients underwent a laparotomy for a pancreatic head tumor. Of these 12 patients, 9 underwent a pylorus-preserving pancreatoduodenectomy and 3 underwent a biliary and gastric bypass procedure. Postoperatively, drain production was measured in milliliters per 24 hours. The abdominal drain was generally removed when drain production was less than 100 mL per 24 hours.

Postoperative complications were scored in all patients. Postoperative

Patients

Patients’ characteristics and intraoperative parameters are summarized in Table I. Ten patients had adenocarcinoma of the pancreatic head, 1 patient had an ampullary tumor, and 1 patient had distal bile duct carcinoma. Four patients suffered from postoperative complications. These patients had all undergone a pancreatoduodenectomy. Patients with postoperative complications were younger, 56 versus 66 years (P = 0.01), and had a trend toward a longer operative time (3.9 versus 6.0 hour; P =

Comments

The present study confirms and extends previous investigations demonstrating that proinflammatory cytokines are released into the peritoneal cavity after elective abdominal surgery.5, 6, 7We herein show that, apart from TNFα and IL-6, the anti-inflammatory cytokine IL-10 also can be found in high concentrations in peritoneal fluid after gastrointestinal surgery. Importantly, peritoneal TNFα levels decreased during follow-up in patients with an unremarkable postoperative course, while in all

References (36)

K Sakamoto et al.
Elevation of circulating interleukin 6 after surgeryfactors influencing the serum level
Cytokine
(1994)
JJ Cullen et al.
Pancreatic anastomotic leak after pancreaticoduodenectomyincidence, significance, and management
Am J Surg
(1994)
D Fröhlich et al.
Perioperative pattern of peritoneal interleukin 8, tumour necrosis factor-alpha, and granulocyte elastase release in human secondary peritonitis
Cytokine
(1997)
RJ Baigrie et al.
Systemic cytokine response after major surgery
Br J Surg
(1992)
P Damas et al.
Cytokine serum level during severe sepsis in human IL-6 as a marker of severity
Ann Surg
(1992)
RT Patel et al.
Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis
Br J Surg
(1994)
JM Badia et al.
Peritoneal and systemic cytokine response to laparotomy
Br J Surg
(1996)
F Kimura et al.
Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy
Am J Gastroenterol
(1996)
K Tsukada et al.
Concentrations of cytokines in peritoneal fluid after abdominal surgery
Eur J Surg
(1993)
M Schein et al.
Hypothesiscompartmentalization of cytokines in intraabdominal infection
Surgery
(1996)

T Propst et al.

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid

Eur J Clin Invest

(1993)

T van der Poll et al.

Endogenous IL-10 protects mice from death during septic peritonitis

J Immunol

(1995)

T Kato et al.

Interleukin 10 reduces mortality from severe peritonitis in mice

Antimicrob Agents Chemother

(1995)

JL Cameron et al.

One hundred and forty-five consecutive pancreaticoduodenectomies without mortality

Ann Surg

(1993)

M Trede et al.

Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality

Ann Surg

(1990)

JH Allema et al.

Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region

Cancer

(1995)

TM Karsten et al.

Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of the pancreatic heada retrospective analysis of 241 consecutive patients

Eur J Surg

(1996)

BW Miedema et al.

Complications following pancreaticoduodenectomy. Current management

Arch Surg

(1992)

Cited by (73)

Role of inflammatory and nutritional markers in predicting complications after pancreaticoduodenectomy
2022, Surgery (United States)
Citation Excerpt :
The reason for the high drain fluid levels is that local inflammation attracts macrophages and leukocytes, which in turn produce cytokines; hence, their intra-abdominal levels are high. The same phenomenon does not occur in the peripheral blood circulation during the early phase.26,27 Our study proved that drain fluid IL-6 is more useful than serum IL-6 as a marker for the early prediction of fistula formation.
Pancreaticoduodenectomy is associated with considerable morbidity and mortality rates. Early recognition of patients likely to develop severe postoperative complications will allow the timely commencement of a tailored approach. This study aimed to predict postoperative complications using inflammatory and nutritional markers measured early in the postoperative period.
Patients who underwent pancreaticoduodenectomy between June 2019 and November 2020 were included in the study. Postoperative pancreatic ﬁstula, delayed gastric emptying, and postoperative pancreatic hemorrhage were graded according to the International Study Group of Pancreatic Fistula and the International Study Group of Pancreatic Surgery. We also documented other complications such as wound infection, intra-abdominal collection, and nonsurgical complications. Nutritional and inflammatory markers were analyzed on postoperative days 1 and 3. Patients were followed up for 30 days or until discharge, depending on which was longer.
Of the 58 enrolled patients, 51 were included in the study. The incidence of postoperative pancreatic ﬁstula was 51% (clinically relevant postoperative pancreatic ﬁstula 27.4%), delayed gastric emptying was 80.4% (clinically relevant delayed gastric emptying 43%), postoperative pancreatic hemorrhage was 3.9%, intra-abdominal collection was 23.5%, and wound infection was 29.4%. The median drain fluid interlukin-6 levels on postoperative day 1 and postoperative day 3 were significantly higher in patients developing clinically relevant postoperative pancreatic ﬁstula than in those who did not develop clinically relevant postoperative pancreatic ﬁstula on postoperative day 1 (211 [125, 425] fg/dL vs 99 [15, 170] fg/dL, [P = .045]) and on postoperative day 3 (110 [22, 28] fg/dL vs 10 [1.8, 45] fg/dL [P = .002]). Patients who tested negative for urine trypsinogen-2 on postoperative day 3 had a significantly lower probability of developing clinically relevant postoperative pancreatic ﬁstula than those who tested positive (1 vs 24 [P < .001]). A model comprising both drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 definitively ruled out the occurrence of clinically relevant postoperative pancreatic ﬁstula.
Drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 ruled out the occurrence of clinically relevant postoperative pancreatic ﬁstula.
Perioperative Simvastatin Therapy in Major Colorectal Surgery: A Prospective, Double-Blind Randomized Controlled Trial
2016, Journal of the American College of Surgeons
Statins have numerous potential benefits relevant to abdominal surgery, and their use has been associated with a reduction in the systemic inflammatory response syndrome, wound infection, and anastomotic leak after colorectal surgery. However, this clinical evidence is limited to retrospective studies. The aim of this study was to prospectively investigate whether perioperative statin therapy can decrease the incidence of complications after major colorectal surgery.
A prospective, double-blind, parallel-group, randomized controlled trial was conducted at 3 tertiary hospitals in New Zealand, between October 2011 and August 2013. Adult patients undergoing elective colorectal resection for any indication or reversal of Hartmann's procedure were randomized with a 1:1 patient allocation ratio to receive either 40 mg oral simvastatin or placebo once daily for 3 to 7 days preoperatively until 14 days postoperatively. The primary outcome was the overall incidence of complications for 30 days postoperatively. Secondary outcomes included the systemic and peritoneal cytokine response (interleukin [IL]-1α, IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]α) on postoperative day 1.
There were 132 patients included in the study (65 simvastatin, 67 placebo). There were no significant differences between the 2 groups at baseline with regard to patient, operation, and disease characteristics. There were no significant differences between the 2 groups in the incidence, grade, and type of postoperative complications (simvastatin: 44 [68%] vs placebo: 50 [75%], odds ratio 0.71 [95% CI 0.33 to 1.52], p = 0.444). Plasma concentrations of IL-6, IL-8, and TNFα, and peritoneal concentrations of IL-6 and IL-8, were significantly lower in the simvastatin group postoperatively.
Perioperative simvastatin therapy in major colorectal surgery attenuates the early proinflammatory response to surgery, but there were no differences in postoperative complications.
Intestinal mast cells in gut inflammation and motility disturbances
2012, Biochimica et Biophysica Acta - Molecular Basis of Disease
Mast cells may be regarded as prototypes of innate immune cells that can be controlled by neuronal mediators. Their activation has been implicated in many types of neuro-inflammatory responses, and related disturbances of gut motility, via direct or indirect mechanisms that involve several mechanisms relevant to disease pathogenesis such as changes in epithelial barrier function or activation of adaptive or innate immune responses. Here we review the evidence for the involvement of mast cells in the inflammation of the bowel wall caused by bowel manipulation that leads to motility disturbances such as postoperative gastroparesis and ileus. Also in IBD there is substantial evidence for the involvement of mast cells and a mast cell-mediated neuroimmune interaction showing an increased number and an increased degranulation of mast cells. We discuss the potential of mast cell inhibition as a bona fide drug target to relief postoperative ileus. Further research on mast cell-related therapy either by stabilizing the mast cells or by blocking specific mast cell mediators as adjunctive therapy in IBD is encouraged, bearing in mind that several drugs currently used in the treatment of IBD possess properties affecting mast cell activities. This article is part of a Special Issue entitled: Mast cells in inflammation.
Peritoneal cytokines as early markers of peritonitis following surgery for colorectal carcinoma: A prospective study
2011, Cytokine
Citation Excerpt :
We found that the cytokine levels significantly increased during the first 3 days in patients with peritonitis, whereas significantly decreased in those without peritonitis. In the normal postoperative course, the peak of peritoneal cytokine production is observed on the first postoperative day and thereafter it decreases with time [8–13]. The increase of peritoneal cytokine production during the first 3 days before the clinical symptoms become apparent should be appropriate markers to predict future intraabdominal complications.
This study was to investigate if measurement of peritoneal cytokines is valuable for an early diagnosis of peritonitis following colorectal surgery. One hundred consecutive patients who were to undergo elective resection for carcinoma of the sigmoid colon or the rectum were investigated. Abdominal exudate was obtained from a drainage tube daily after surgery for measuring interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. The relationship between peritoneal cytokine levels during the first 3 days after surgery and the development of peritonitis was investigated. Eight patients developed postoperative peritonitis due to anastomotic leakage and pelvic abscess, which was diagnosed on postoperative days 5–8. Peritoneal cytokine levels on postoperative days 1 and 2 were not significantly different between the 8 patients who developed peritonitis and 92 patients who did not: day 1, IL-1β P = 0.32, IL-6 P = 0.45, TNF-α P = 0.85; day 2, IL-1β P = 0.26, IL-6 P = 0.68, TNF-α P = 0.22. In contrast, the cytokine levels on day 3 were significantly higher in patients who developed peritonitis as compared with patients who did not: IL-1β P = 0.008, IL-6 P < 0.0001, TNF-α P = 0.0001. The cytokines significantly increased during the first 3 days in patients who developed peritonitis: IL-1β P = 0.049, IL-6 P = 0.03, TNF-α P = 0.01, while significantly decreased in patients who did not: IL-1β P < 0.0001, IL-6 P < 0.0001, TNF-α P < 0.0001. The outcomes of this investigation showed that the rise in peritoneal IL-1β, IL-6 and TNF-α levels may be an additional early diagnostic predictor of intraabdominal complications following colorectal surgery.
The unrestricted global effort to complete the COOL trial
2023, World Journal of Emergency Surgery
The Unrestricted Global effort to complete the Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (COOL) Trial
2023, Research Square

View all citing articles on Scopus

¹: T. van der Poll is a fellow of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.

View full text

Scientific PapersPeritoneal Cytokine Release after Elective Gastrointestinal Surgery and Postoperative Complications

Abstract

Section snippets

Patients

Patients

Comments

Cytokine

Am J Surg

Cytokine

Systemic cytokine response after major surgery

Br J Surg

Cytokine serum level during severe sepsis in human IL-6 as a marker of severity

Ann Surg

Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis

Br J Surg

Peritoneal and systemic cytokine response to laparotomy

Br J Surg

Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy

Am J Gastroenterol

Concentrations of cytokines in peritoneal fluid after abdominal surgery

Eur J Surg

Hypothesiscompartmentalization of cytokines in intraabdominal infection

Surgery

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid

Eur J Clin Invest

Endogenous IL-10 protects mice from death during septic peritonitis

J Immunol

Interleukin 10 reduces mortality from severe peritonitis in mice

Antimicrob Agents Chemother

One hundred and forty-five consecutive pancreaticoduodenectomies without mortality

Ann Surg

Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality

Ann Surg

Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region

Cancer

Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of the pancreatic heada retrospective analysis of 241 consecutive patients

Eur J Surg

Complications following pancreaticoduodenectomy. Current management

Arch Surg

Scientific Papers
Peritoneal Cytokine Release after Elective Gastrointestinal Surgery and Postoperative Complications