Glatz et al. BMC Surgery (2015) 15:108 DOI 10.1186/s12893-015-0097-y RESEARCH ARTICLE Open Access The degree of local inflammatory response after colonic resection depends on the surgical approach: an observational study in 61 patients Torben Glatz*, Ann-Kathrin Lederer, Birte Kulemann, Gabriel Seifert, Philipp Anton Holzner, Ulrich Theodor Hopt, Jens Hoeppner and Goran Marjanovic Abstract Background: Clinical data indicate that laparoscopic surgery reduces postoperative inflammatory response and benefits patient recovery. Little is known about the mechanisms involved in reduced systemic and local inflammation and the contribution of reduced trauma to the abdominal wall and the parietal peritoneum. Methods: Included were 61 patients, who underwent elective colorectal resection without intraabdominal complications; 17 received a completely laparoscopic, 13 a laparoscopically- assisted procedure and 31 open surgery. Local inflammatory response was quantified by measurement of intraperitoneal leukocytes and IL-6 levels during the first 4 days after surgery. Results: There was no statistical difference between the groups in systemic inflammatory parameters and intraperitoneal leukocytes. Intraperitoneal interleukin-6 was significantly lower in the laparoscopic group than in the laparoscopically-assisted and open group on postoperative day 1 (26.16 versus 43.25 versus 40.83 ng/ml; p = 0.001). No difference between the groups was recorded on POD 2–4. Intraperitoneal interleukin-6 showed a correlation with duration of hospital stay on POD 1 (0.233, p = 0.036), but not on POD 2–4. Patients who developed a surgical wound infection showed higher levels of intraperitoneal interleukin-6 on postoperative day 2–4 (POD 2: 42.56 versus 30.02 ng/ml, p = 0.03), POD 3: 36.52 versus 23.62 ng/ml, p = 0.06 and POD 4: 34.43 versus 19.99 ng/ml, p = 0.046). Extraabdominal infections had no impact. Conclusion: The analysis shows an attenuated intraperitoneal inflammatory response on POD 1 in completely laparoscopically-operated patients, associated with a quicker recovery. This effect cannot be observed in patients, who underwent a laparoscopically-assisted or open procedure. Factors inflicting additional trauma to the abdominal wall and parietal peritoneum promote the intraperitoneal inflammation process. Keywords: Laparoscopic surgery, Laparoscopically-assisted surgery, Peritoneal inflammation, Cytokines, Wound healing Background Laparoscopic surgery has been shown to attenuate both Major abdominal surgery and laparotomy causes a release local and systemic inflammatory response [8–13]. of local and systemic cytokines, inducing a systemic in- Today, minimally-invasive bowel resection has been flammatory response syndrome [1–3]. Local peritoneal in- established as a standard procedure in most hospitals. flammation is thought to play a role in patient recovery Retrospective analyses indicate a beneficial effect of lap- and in development of perioperative complications [4–7]. aroscopically- performed surgery on patient recovery and even on the occurrence of serious complications like anastomotic leak and on patient survival [14–17]. In an attempt to quantify the systemic and local im- * Correspondence: [email protected] pact of laparoscopic surgery on the inflammatory re- Department of General and Visceral Surgery, Albert Ludwigs University of sponse, systemic and intraperitoneal (ip) interleukin-6 Freiburg, Freiburg im Breisgau, Germany © 2015 Glatz et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Glatz et al. BMC Surgery (2015) 15:108 Page 2 of 7 (IL-6) has been established as a sensitive marker of in- the anastomosis through a small lower medial laparot- flammation on postoperative day 1 after surgery. Low ip omy (6–12 cm), while the completely laparoscopic oper- levels of IL-6 are associated with faster recovery and ation was characterized by laparoscopic fashioning of earlier hospital discharge [13, 18]. Several studies show the anastomosis and removal of the resected bowel lower levels of systemic IL-6 on day 1 after laparoscopic through a suprapubic mini-laparotomy (3–5 cm) after surgery [12], while only one study exists illustrating the complete laparoscopic mobilization. Our definitions are effect of laparoscopic surgery on ip IL-6 [13]. All others concordant with the literature [24, 25]. studies have failed to establish a difference in intraperi- Postoperatively, patients received standardized pain toneal cytokines between laparoscopic and conven- medication (metamizole, oxycodone and piritramide). tional surgery [19–21]. Most of these studies did not Anti-inflammatory drugs were omitted whenever possible. include completely laparoscopic operations, but only laparoscopically-assisted procedures with laparotomy after colonic mobilization, which might induce an in- Sample collection and storage creased local inflammatory response compared to a Patients included in the study had a 10 mm Intersil® completely laparoscopic procedure. The aim of this Silicone X-Ray Capillary Drain (Mikrotek® medical, study is to determine whether postoperative intraperi- Mosta, MT) inserted into the Douglas cavity during toneal inflammation depends on the surgical technique surgery. The intraperitoneal fluid was collected in a and the trauma inflicted on the abdominal wall by collecting bag (Urine bag, Asis Bonz®, Herrenberg, quantifying local inflammatory response via ip IL-6 DE). The drain was removed on postoperative day 4 levels during the first days after colorectal surgery in after collection of samples. patients undergoing a completely laparoscopic, a Drainage clearance was performed daily at 6 am. Two laparoscopically-assisted or an open procedure. to four hours later, fresh drainage fluid was collected on POD 1–4 and venous blood samples were taken on Methods POD 1, 3, and 5. All samples were sent immediately to Patients and operative procedure the Freiburg university hospital laboratory for further The observational study includes 61 consecutively oper- analyses. ated patients, who underwent elective colorectal resec- tion from January to December 2013 at our institution. Parameter analyses Only patients without major intraabdominal complica- Analyzed were serum leukocytes on POD 1, 3 and 5 and tions were included. Informed consent was obtained serum c-reactive protein (CRP) on POD 3 and 5 as part from all patients before operation and inclusion in the of the routine follow-up. Intraperitoneal leukocytes and study. Institutional Review Board approval was granted IL-6 were measured on POD 1–4. In 6 patients, meas- for the sample collection and evaluation of patient urement of intraperitoneal leukocytes was not possible demographics (EK-F: 345/12) by the Medical Ethics due to lack of material. On POD 4, the drain had already Committee of the University of Freiburg, the study was been removed in 9 patients, thus no material was taken carried out according to the Helsinki Declaration. Data for analyses. Parameter analyses were performed with were collected with regard to patient demographics, the modular analyzer Cobas® 8000 (Roche® Diagnostics, details of disease, operative procedure and extraab- Rotkreuz, Risch, CH) for IL-6 and CRP and the XN- dominal complications. Complications were defined by 9000® (Sysmex® Corporation, Kobe, JP) for leukocytes. standardized definitions and graded according to the Clavien-Dindo classification [22, 23]. Procedures included in the study were left-sided colon Statistical analysis resections (sigmoid resection [n = 21], left hemicolect- Results are expressed as mean ± SD and medians with omy [n = 19]) and anterior rectum resection (n = 21). All range, as appropriate. The primary outcome parameter operations were performed by or under supervision of was ip IL-6, the secondary outcome measures were ip experienced colorectal surgeons. The surgical approach leukocytes, systemic leukocytes, CRP and patient demo- (laparoscopic, laparoscopically-assisted or open) was graphics. Differences between categorical variables were chosen by the operating surgeon. Patients were not ran- evaluated by Fisher’s exact test. Differences between domized to the groups. The patients were retrospectively continuous variables were measured using the Kruskal- assigned to the group according to the operation tech- Wallis test or Mann–Whitney-U-test, as appropriate. ™ nique. Four operations were converted from laparo- SPSS for Windows was used for statistical analysis scopic to open and were assigned to the open group. (SPSS, Chicago, IL, USA). A Spearman’s correlation coef- The laparoscopically-assisted procedure was defined as a ficient was employed to express the correlations. P <0.05 laparoscopic mobilization of the colon and fashioning of was considered significant. Glatz et al. BMC Surgery (2015) 15:108 Page 3 of 7 Results Patient demographics, surgical technique and Patients intraperitoneal IL-6 Among the 61 patients, 17 were operated completely Mean total values of ip IL-6 were very high