Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastrointest Surg. Apr 27, 2013; 5(4): 73-82
Published online Apr 27, 2013. doi: 10.4240/wjgs.v5.i4.73
Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis
Federico Sista, Mario Schietroma, Giuseppe De Santis, Antonella Mattei, Emanuela Marina Cecilia, Federica Piccione, Sergio Leardi, Francesco Carlei, Gianfranco Amicucci
Federico Sista, Mario Schietroma, Giuseppe De Santis, Emanuela Marina Cecilia, Federica Piccione, Sergio Leardi, Francesco Carlei, Gianfranco Amicucci, Department of Surgery, University of L’Aquila, 67100 Coppito, Italy
Antonella Mattei, Department of Medicine, Health and Environment Sciences, University of L’Aquila, 67100 Coppito, Italy
Author contributions: Sista F, Schietroma M and Amicucci G designed the study and wrote the manuscript; De Santis G, Cecilia EM and Piccione F performed the data collection; Leardi S and Carlei F coordinated the collection of all the data and reviewed the scientific literature; Mattei A performed the statistical analysis.
Correspondence to: Federico Sista, MD, Department of Surgery, University of L’Aquila, Piazza Rivera, 1, 67100 Coppito, Italy. silversista@gmail.com
Telephone: +39-349-8508308 Fax: +39-348-6222375
Received: August 5, 2012
Revised: January 17, 2013
Accepted: February 5, 2013
Published online: April 27, 2013
Abstract

AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach.

METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 °C, leukocytosis greater than 10 × 109/L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis, complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-op day 6.

RESULTS: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphocyte subpopulations showed no significant variation. On the first day after surgery, a statistically significant difference was observed in HLA-DR expression between LC (13.0 ± 5.2) and OC (6.0 ± 4.2) (P < 0.05). A statistically significant change in plasma elastase concentration was recorded post-operatively at days 1, 3, and 6 in patients from the OC group when compared to the LC group (P < 0.05). In the OC group, the serum levels of IL-1 and IL-6 began to increase considerably from the first to the sixth hour after surgery. In the LC group, the increase of serum IL-1 and IL-6 levels was delayed and the peak values were notably lower than those in the OC group. Significant differences between the groups, for these two cytokines, were observed from the second to the twenty-fourth hour (P < 0.05) after surgery. The mean values of serum CRP in the LC group on post-operative days (1 and 3) were also lower than those in the OC group (P < 0.05). Systemic concentration of endotoxin was higher in the OC group at all intra-operative sampling times, but reached significance only when the gallbladder was removed (OC group = 36.81 ± 6.4 ρg/mL vs LC group = 16.74 ± 4.1 ρg/mL, P < 0.05). One hour after surgery, microbiological analysis of blood cultures detected 7 different bacterial species after laparotomy, and 4 species after laparoscopy (P < 0.05).

CONCLUSION: OC increased the incidence of bacteraemia, endotoxaemia and systemic inflammation compared with LC and caused lower transient immunological defense, leading to enhanced sepsis in the patients examined.

Keywords: Systemic inflammation, Immune response, Laparoscopy, Cholecystectomy, Bile peritonitis

Core Tip: Laparoscopic techniques are being increasingly used in diffuse or localised peritonitis. However, a possible concern is that increased intra-abdominal pressure may promote bacteraemia and the systemic inflammatory response during laparoscopic surgery. The majority of reports in the literature are on experimental studies made using animal models. This study, instead, is a prospective randomized study conducted on human subjects. Experimental studies on peritonitis showed that the inflammatory response was significantly higher in the open cholecystectomy (OC) group than in the laparoscopic cholecystectomy (LC) group in the animal models, suggesting that carbon dioxide pneumoperitoneum has a protective effect against bacterial peritonitis. This study, in contrast to the previous ones, is the first work demonstrating that OC after biliary peritonitis increases the incidence of bacteraemia, endotoxaemia and systemic inflammation, compared with the LC group. The authors also demonstrated that early enhanced post-operative systemic inflammation may cause lower transient immunologic defense after laparotomy (decrease of human leukocyte antigen-DR), leading to increased sepsis in these patients.