Katarzyna Borycka-Kiciak, Naser Dib, Łukasz Janaszek, Łukasz Sołtysiak, Barbara Bukowicka, Wiesław Tarnowski

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1 POLSKI PRZEGLĄD CHIRURGICZNY 2013, 85, 9, /pjs Laparoscopically assisted ileo-colonic resection in patients with Crohn s disease preliminary report Katarzyna Borycka-Kiciak, Naser Dib, Łukasz Janaszek, Łukasz Sołtysiak, Barbara Bukowicka, Wiesław Tarnowski Department of General, Oncological and Gastrointestinal Surgery, Orłowski Hospital MCPE in Warsaw Kierownik: prof. dr hab. W. Tarnowski Despite increasing number of reports indicating good treatment outcomes, laparoscopic treatment of Crohn s disease remains controversial. The aim of the study was to compare outcomes of laparoscopically assisted and open ileo-colonic resection in patients with active Crohn s disease. Material and methods. 82 patients who underwent surgical treatment (44 laparoscopic and 38 open procedures) at the Department of General, Oncological and Gastrointestinal Surgery in Warsaw were enrolled to the study. The following perioperative parameters were compared in both these groups: duration of hospitalization and presence of postoperative complications in at least 12 months of follow up. Results. The conversion rate in the laparoscopy group was 29.5%. There were no statistically significant differences between the study groups with regard to duration of the surgical procedure, requirement for perioperative transfusions and total number of postoperative complications (19.3% in the laparoscopy group versus 28.9% in the open surgery group). However, amount of analgesic drugs required in the postoperative period was significantly lower (25±6 vs 43±9, p<0.01) and duration of hospitalization was significantly shorter (9.0 vs 11.3 days, p=0.021) after laparoscopic versus open procedures procedures. Most of the patients with complicated Crohn s disease who were qualified to laparoscopic treatment, underwent successful treatment using this method. Patients in whom conversion was done, were more likely to be on long term preoperative immunosuppressive therapy versus other patients. Conclusions. Laparoscopy is a demanding procedure from the technical point of view, but provides valuable benefits to patients with Crohn s disease, including those with a complicated disease. However, this method requires ongoing improvement of technical aspects and thorough analysis of failures to identify factors that could accurately select patients with indications and contraindications to this procedure. Key words: laparoscopy, Crohn s disease, postoperative complications Just as in other areas of surgery, laparoscopy found it place also in the treatment of nonspecific inflammatory bowel disease. If managed by a skilful and experienced operator, its results are as good as those of an open procedure or even better in some aspects (1-6). Improved cosmetic effect, reduced postoperative pain, lower intraoperative blood loss, more rapid restoration of gastrointestinal function and shorter hospitalization and eventual recovery of full activity make this method especially desirable in the group of young patients with Crohn s disease who have already used majority of available medical treatment methods, since majority of them will require multiple extensive abdominal surgical procedures. However, in routine practice laparoscopy is reluctantly considered in this group of patients as an alternative method (7). This results from the fact that surgical treatment of multilevel,

2 506 K. Borycka-Kiciak et al. often complicated disease, requiring dissection and anatomoses in the tissues affected by inflammation, is often very difficult even for open surgical procedures, while laparoscopy, with its technical demands and long learning curve may seem too demanding. The aim of this study was to compare outcomes of laparoscopically assisted and open ileo-colonic resection in two groups of patients with active Crohn s disease. Material and methods The study enrolled 44 patients who underwent attempted laparoscopically assisted ileocolonic resection due to Crohn s disease and a matched group of 38 patients who underwent an open surgical procedure for the same reason between July 2008 and May 2012 at the Department of General, Oncological and Gastrointestinal Surgery, Orłowski Hospital MCPE in Warsaw. The decision related to type of a surgical procedure was undertaken by one of 2 surgeons colorectal specialists basing on their clinical experience. Patients with a disease at other locations as well as previously operated patients were also qualified to laparoscopic procedures. Preoperative assessment of the extent of the disease included colonoscopy, gastrointestinal passage and computed tomography of the abdomen and pelvis. All procedures were performed under general anesthesia, following placement of a catheter to the epidural space to allow for postoperative analgesic management. All patients also received antithrombotic prophylaxis and antibiotic prophylaxis according to current guidelines. Laparoscopic technique Patients were positioned in a modified lithotomy position, with their left hand extending along their body. A subumbilical 10 mm trocar was inserted through minilaparotomy and after pneumoperitoneum was achieved, another 3 trocars were inserted under visual guidance: 5 mm in the right epigastric area, 10 mm in the left epigastric area and 5 mm in the suprapubic region. During this procedure an operator was standing on the left side of the patient, holding a harmonic scalpel or LigaSure and a dissector. The assistant was standing initially on the right side of the patient, then on the right side, manipulating with a camera and retractor. Following inspection of abdominal organs and scheduling the extent of the procedure, the terminal part of the ileum, the cecum and the ascending colon until the hepatic flexure were freed, exposing the right ureter and duodenum. After the intestinal fragment to be resected was freed, a 4 5 cm minilaparotomy incision was made in the right epigastric region, a wound-protector was inserted and the preparation was removed. Subsequently, under visual guidance, a ileo-ascending colon anastomosis or ileo-transverse colon isoperistaltic anastomosis was done, side-to-side, using a reusable stapler GIA 90 mm (DST Series, Covidien, Ireland). If there were any additional strictures in the small intestine, a segmental intestinal resection was made with a wide side-to-side anastomosis with a simple stapler GIA 60 mm. Each time after the abdominal procedure a corrugated drain was left in the abdominal cavity. A requirement for extension of a minilaparotomy incision was considered as a conversion of the procedure. Open technique Using a midline incision around the umbilicus, the terminal segment of the ileum, the cecum and the ascending colon were freed using LigaSure, and dissection was done as close to the intestine as possible. After removal of the preparation, a wide ileo-ascending colon anastomosis or ileo-transverse colon isoperistaltic anastomosis was done, side-toside, using a reusable stapler GIA 90 mm (DST Series, Covidien, Ireland). If there were any additional lesions in the small intestine, resection with side-to-side anastomosis was done. A corrugated drain was left in the abdominal cavity. Statistical analysis The following parameters were assessed: age, sex, BMI, duration of the disease, number of relapses and previous therapy, presence of preoperative risk factors of postoperative complications and presence of additional factors

3 Laparoscopically assisted ileo-colonic resection in patients with Crohn s disease preliminary report 507 in each of the groups to assess their comparability. The perioperative period in the laparoscopy group was similar to that in the open group following establishment of the conversion rate with regard to duration of the procedure, perioperative blood loss, time to return of the peristalsis, amount of analgesic drugs required during the first 72 hours after the surgical procedure, duration of hospitalization and presence of postoperative complications during at last 12 months of follow-up (12-36 months). Answers to the surveys, such as yes/no, lack/ present were converted in tables to binary form, where FALSE(no) = 0 and TRUE(yes) = 1. t-student s test or nonparametric Mann- Whitney test were used to compare the 2 study groups. The analysis was conducted using the software GraphPad Prism v.5.02 for Windows (GraphPad Software, San Diego California USA, p < 0.05 was considered statistically significant, while p = was considered a trend. Results Eighty two patients (34 men and 48 women) with ileocecal location of Crohn s disease underwent surgical treatment at the Department of General, Oncological and Gastrointestinal Surgery, Medical Centre of Postgraduate Education in Warsaw between July 2008 and May A laparoscopic procedure was attempted in 44 patients, but 13 patients were converted, while 38 persons were operated using an open procedure as planned. Table 1 provides characteristics of the patient groups. The conversion rate in the laparoscopy group was 29.5%. Further analysis was limited to 31 patients who underwent a laparoscopic procedure (LS group) and 38 patients who underwent an open procedure (LT group). An average duration of the laparoscopic procedure was 138 minutes and was comparable to duration of an open procedure that was 125 min (p=0.21). 6.5% patients who underwent laparoscopic treatment and 15.7% patients who underwent an open procedure required perioperative blood transfusion (p = 0.234). Restoration of peristalsis was recorded on average on day 2 after the surgery in the LS group and on day 3 after the laparotomy. 10.5% (4) patients after laparotomy and none of the patients who underwent laparoscopic treatment required parenteral nutrition. All patients received standard analgesic regimen in the postoperative period (marcaine Table 1. Patient characteristics Laparoscopy n=44 Laparotomy n=38 n % n % Age 32 years (21-55) 32 years (22-61) Sex - women - men Cigarette smoking 4 9,1 4 10,5 Average disease duration (months) 56 (5-114) 51 (6-126) Number of recurrences 3 (1-10) 2,8 (1-9) Preoperative steroid therapy 23 52, ,1 Preoperative azathioprine/mercaptopurin therapy 21 47, ,4 Biological therapy 5 11,4 1 2,6 Preoperative abscess or fistula 6 13,6 8 21,05 First operations 36 81, ,7 Repeated operation 8 18,2 2 5,3 Average BMI 17,27 19,5 Loss of body weight >10% 7 15, ,5 Serum total protein (n=6-8 g/dl) 6,76 6,25 Average serum albumin (n=3.5-5 g/dl) 3,52 3,16 Preoperative parenteral nutrition ,2

4 508 K. Borycka-Kiciak et al. + Dolargan + 0.9% NaCl) as a continuous infusion through the epidural catheter. Patients who underwent laparoscopic treatment required such management on average for 25 ± 6 hours at an average dose of 6 ml/hour, while the requirement for analgesic drugs in the LT group was on average 10 ml/hour for an average of 43 ± 9 hours after the procedure (p<0.01). An average duration of hospitalization was 9.0 days in the patients who underwent laparoscopic treatment and was significantly shorter than in the group of patients who underwent an open procedure (11.3 days, p = 0.021); the surgical procedure was usually done on day two after the hospital admission. Complications in the early postoperative period were observed in 19.3% of patients in the LS group and 28.9% patients in the LT group (statistically insignificant difference). Incidence of individual complications in both study groups is provided in tab. 2. One patient who underwent laparoscopic treatment (3.2%) required reoperation due to bleeding on day one after the surgery and 3 patients who underwent an open procedure (5.2%) one patient due to postoperative ileus and two patients due to an extensive intraabdominal abscess. Long-term follow up demonstrated fistulae in 3 patients: intestinal fistula and cutaneointestinal fistula and in one patient (3.2%) from the laparoscopy group and in 2 patients (5.2%) from the laparotomy group. An intraabdominal abscess was found in 1 patient (who underwent an open procedure). All these pathologies should be treated as clinical manifestations of the disease recurrence. No intestinal stricture, hernia in the postoperative wound, adhesion-related ileus or death was found in the whole operated group during the follow-up period. Characteristics of converted patients did not differ from the characteristics of the other groups with except for incidence of steroid therapy (76.9% of patients from this group) and immunosuppressive therapy (61.5% patients) that were more common in this group than in the other groups. Numerous intraabdominal adhesions, bleeding and technical difficulties were the main reasons for conversion. However, only in 3 of 13 cases of conversion this was a case of reoperation. Early complications were found in 4 patients from this group (30.7%). These included: wound infection (2), bleeding (1) and leakage of the anastomosis (1). Discussion Experience of these authors supported literature reports (1, 3, 4, 6, 8, 9, 10), documenting benefits of laparoscopic therapy in patients with ileocecal location of Crohn s disease. Patients with smaller perioperative injury required less analgesics (25±6 vs 43±9 hours) and returned to activity sooner and therefore were discharged from the hospital significantly sooner (9 vs 11.3 days). Incidence of postoperative complications was comparable in both these groups, however there were some clear trends with regard to characteristics of these both groups. Higher incidence of postoperative wound infections and intraabdominal abscess was found in the open surgery group. This can be explained by higher susceptibility to infection in patients with extensive laparotomy incision and extended intraabdominal manipulations, especially in view of the fact that these patients, due to their underlying disease, are often malnourished and have a history of exhausting immunosuppressive Table 2. Incidence of early postoperative complications in the study groups LS group (n=31) LT group (n=38) n % n % Early complications 6 19, ,9 Wound infection 3 9,7 7 18,4 Bleeding 1 3,2 0 Urinary tract infection 1 3,2 0 Postoperative ileus 0 1 2,6 Leakage of the anastomosis 0 0 Intraabdominal abscess 1 3,2 3 7,9

5 Laparoscopically assisted ileo-colonic resection in patients with Crohn s disease preliminary report 509 therapy. Effect of these factors on increased risk of serious complications, in particular septic complications, in the postoperative period in patients with IBD was confirmed many times (11 14). The fact that there are multiple known risk factors of postoperative complications is one of the reasons for surgeons to avoid laparoscopic procedures in patients with Crohn s disease. Nevertheless, according to authors, a long standing immunosuppressive therapy before the surgical therapy should rather make the operator consider the possibility of laparoscopic procedure instead of being a contraindication to it. Literature reports indicate increased incidence of perioperative bleeding after laparoscopic procedures (15) conducted for the treatment of Crohn s disease. Markedly thickened and highly vascular mesentery favors this. Therefore the recommended management of this group (16) involves external management of blood vessels which seems safer and related to fewer bleeding complications. Such management is also the standard procedure at the authors site, but this did not prevent intraoperative bleeding from occurring. Such bleeding events were found in 3 patients, and in 2 of them they even resulted in conversion. As experience of many authors dictates, it is often difficult to compare outcomes of laparoscopic and open procedures. This results from differences in characteristics of patients qualified to these procedures. Usually younger patients, without comorbidities, in better general health, without a history of complex therapies, without malnourishment or intestinal fistulae are qualified to laparoscopic procedures (7). In our study patients were qualified to laparoscopic procedures irrespective of age and medical history, however the procedure was always performed in an elective setting, following adequate preparation. With regard to the disease activity, the study population was a real setting population rather than a selected group of patients. This also applies to complications of Crohn s disease (defined as a presence of fistula, abscess, multilevel disease or a history of surgical treatment). No correlation was found between the disease activity and incidence of postoperative complications in the laparoscopy group, although such correlation was reported by some authors (17) indicating higher rate of complications after a laparoscopic procedure in patients with higher disease activity (higher CRP level) and lower initial hemoglobin level. Our study group included 6 patients with preoperative fistula or an abscess and 8 previously operated patients who were qualified to laparoscopic procedure. Majority of these patients underwent successful laparoscopic procedure. Benefits of laparoscopic treatment in patients with a history of abdominal procedures were also confirmed by other authors (18, 19, 20). Presence of fistulae for many years was considered as a negative predictive factor of outcome following laparoscopic procedures (7). Operators were less eager to qualify patients with fistulae related to Crohn s disease to laparoscopic treatment due to concerns over technical difficulties. However current reports support safety and benefits of laparoscopic procedures also in patients with fistulae (21). The conversion rate in the study population was 29.5% and significantly differed from that found by other authors in their patient groups who underwent laparoscopic treatment (for the sake of comparison, it was 13% in patients with colorectal tumors). However, it was similar to the rate reported by other authors (16 25%) in the group of patients with Crohn s disease (8, 22, 23). Such incidence clearly must have been affected by the underlying disease itself and its complications, such as: presence of an inflammatory mass (15). A history of surgical treatment was not found to be a negative predictive factor of successful therapy, because the procedure was successful in 5 patients with such history from our group, while in 10 other patients, who underwent first surgical procedure, the operator was forced to convert due to technical difficulties. Similar observations were reported by other authors (20, 22). In our study group, despite small sample size, we found that majority of converted patients had a history of chronic immunosuppressive therapy, steroid therapy or treatment with purin analogs. It is difficult to assess the relevance of this fact, however high conversion rate reported by many authors should facilitate thorough analysis of this group in subsequent studies. This could lead to identification of risk factors of failure of laparoscopic treatment and establishment of accurate indications to such treatment in this difficult group patients with Crohn s disease.

6 510 K. Borycka-Kiciak et al. Conclusions Laparoscopy is a demanding procedure from a technical point of view, but it provides valuable benefits to patients with an active Crohn s disease, including complicated disease. However, this method requires ongoing improvement of technical aspects and thorough analysis of failures to identify factors that could accurately select patients with indications and contraindications to this procedure. references 1. Bemelman WA, Slors JF, Dunker MS, van Hogezand RA et al.: Laparoscopic-assisted vs. open ileocolic resection for Crohn s disease. A comparative study. Surg Endosc 2000; 14: Bemelman WA, Dunker MS, Slors JF et al.: Laparoscopic surgery for inflammatory bowel disease: current concepts. Scand J Gastroenterol Suppl 2002; 37: Gurland BH, Wexner SD: Laparoscopic surgery for inflammatory bowel disease: results of the past decade. Inflamm Bowel Dis 2002; 8: Maartense S, Dunker MS, Slors JF et al.: Laparoscopic-assisted versus open ileocolic resection for Crohn s disease: a randomized trial. Ann Surg 2006; 243: ; discussion Tilney HS, Constantinides VA, Heriot AG et al.: Comparison of laparoscopic and open ileocecal resection for Crohn s disease: a meta-analysis. Surg Endosc 2006; 20: Tan L, Tjandra JJ: Laparoscopic surgery for Crohn s disease: a meta-analysis. Dis Colon Rectum 2007; 50: Ananthakrishnan AN, McGinney EL, Saeian K et al.:laparoscopic resection for Inflammatory Bowel Disease: outcomes from a nationwide sample. J Gastrointest Surg 2010; 14: Polle SW, Wind J, Ubbink DT et al.: Short-term outcomes after laparoscopic ileocolic resection for Crohn s disease. A systematic review. Dig Surg 2006; 23(5-6): Milsom JW, Hammerhofer KA, Böhm B et al.: Prospective, randomized trial comparing laparoscopic vs. conventional surgery for refractory ileocolic Crohn s disease. Dis Colon Rectum 2001; 44: Milsom JW: Laparoscopic surgery in the treatment of Crohn s disease. Surg Clin North Am 2005; 85: Alves A, Panis Y, Bouhnik Y et al.: Factors that predict conversion in 69 consecutive patients undergoing laparoscopic ileocecal resection for Crohn s disease: a prospective study. Dis Colon Rectum 2005; 48: Meijerink WJ, Eijsbouts QA, Cuesta MA et al.: Laparoscopically assisted bowel surgery for inflammatory bowel disease. The combined experience of two academic centers. Surg Endosc 1999; 13: Myrelid P, Olaison G, Sjodahl R et al.: Thiopurine therapy is associated with postoperative intraabdominal septic complications in abdominal surgery for Crohn s disease. Dis Colon Rectum 2009; 52: White EC, Melmed GY, Vasiliauskas E et al.: Does preoperative immunosuppression influence unplanned hospital readmission after surgery in patients with Crohn s disease? Dis Colon Rectum 2012; 55: Diamond IR, Gerstle JT, Kim PC et al.: Outcomes after laparoscopic surgery in children with inflammatory bowel disease. Surg Endosc 2010; 24: Talamini MA, Moesinger RC, Kaufman H et al.: Laparoscopically assisted bowel resection for Crohn s disease. Digestive Disease Week Abstract Book. 17. Riss S, Bittermann C, Schwameis K et al.: Determinants for postoperative complications after laparoscopic intestinal resection for Crohn s disease. Surg Endosc 2012; 26(4): Pinto RA, Shawki S, Narita K et al.: Laparoscopy for recurrent Crohn s disease: how do the results compare with the results for primary Crohn s disease? Colorectal Dis 2011; 13: Chaudhary B, Glancy D, Dixon AR: Laparoscopic surgery for recurrent ileocolic Crohn s disease is as safe and effective as primary resection. Colorectal Dis 2011; 13: Huang R, Valerian BT, Lee EC: Laparoscopic approach in patients with reccurent Crohn s disease. Am Surg 2012; 78: Beyer-Berjot L, Mancini J, Bege T et al.: Laparoscopic approach is feasible in Crohn s complex enterovisceral fistulas: a case-match review. Dis Colon Rectum 2013; 56: Edden Y, Ciardullo J, Sherafgan K et al.: Laparoscopic-assisted ileocolic resection for Crohn s disease. JSLS 2008; 12: Holubar SD, Dozois EJ, Privitera A et al.: Laparoscopic surgery for recurrent ileocolic Crohn s disease. Inflamm Bowel Dis 2010; 16(8): Received: r. Adress correspondence: Warszawa, ul. Czerniakowska Kborycka@interia.pl