1. Laparoscopic Treatment of Crohn’s Disease: Is It the Standard Approach? Steven D Wexner, MD, FACS, FRCS, FRCS (Ed) Chairman, Department of Colorectal Surgery 21 st Century Oncology Chair in Colorectal Surgery Chief of Staff Cleveland Clinic Florida Professor of Surgery, Ohio State University Health Sciences Center at the Cleveland Clinic Foundation Clinical Professor of Surgery, University of South Florida College of Medicine Clinical Professor of Biomedical Science Department of Biomedical Science Florida Atlantic University College of Medicine Marat Khaikin, MD Clinical Research Fellow

2. Cleveland Clinic Florida

3. Laparoscopy for Crohn’s disease Case Series AuthorNConversion (%) Morbidity (%) Hospital Stay (days) Milsom, Surg Laparosc Endosc ‘93 9007 Bauer, DCR ‘95 1822116.6 Reissman, Surg Endosc ‘96 5114 5.1 Ludwig, Am J Surg ‘96 311936 Canin-Endres, Surg Endosc ‘99 88184.2 Schmidt, Ann Surg ‘01 11040136 Hamel, Am Surg ‘02 13018118.8 Evans, DCR ‘02 841810.75.6

4. Laparoscopy for Crohn’s disease Comparative Studies AuthorStudyLap/Open (n) Oper.time (min) Conversion (%) Morbidity (%) Hospital stay (days) Bemelman, 2000 Case-control 30/48138/1046.610/14.65.7/10.2 Alabaz, 2000 Case-control 26/48150/90.511.515.4/16.77/9.6 Milsom, 2001 RCT 31/29140/85612.9/27.65/6 Young-Fadok, 2001 Case-match 33/33147/1245.9-4/7 Msika, 2001 Prospective Case-control 20/26302/244.709.5/18.58.3/13.2 Duepree, 2002 Case-control 21/2475/984.814.3/16.73/5 Bergamaschi, 2003 Case-control 39/53185/105010.2/9.45.6/11.2 Shore, 2003 Case-control 20/20145/133.550/54.25/8.25 Benoist, 2003 Case-match 24/32179/1981720/107.7/8 Huilgol, 2004 Case-control 21/19136/119.54.819/15.86.4/8.2 Bold, statistically significant difference (p<0.05)

5. Laparoscopy for Crohn’s Disease VariableLaparotomyLaparoscopyP Value N4826 Age (years) 41.640NS Gender (m/f) 31/1718/8NS Duration (years)6.85.9NS Operative time (min) 90.5150<0.0001 Hospital Stay (days) 9.67<0.05 Charges ($) 28,25934,657NS Alabaz et al. Eur J Surg 2000

6. Laparoscopy for Crohn’s Disease VariableLaparotomyLaparoscopyP Value Postoperative narcotics (days) 6.32.1<0.001 “Good cosmesis” 13 (42%)14 (88%)0.004 Social/Sexual (vs preoperative) 5 (16%) 8 (50%)0.02 Return to normal activity (weeks) 8.23.7<0.05 Return to work (weeks) 9.34.4<0.05 Alabaz et al. Eur J Surg 2000

7. Laparoscopy for Crohn’s Disease VariableLaparotomyLaparoscopyP Value Bowel obstruction (symptomatic) 15 (31%)2 (8%)<0.05 Relaparotomy 4 (8%)1 (4%)NS Adhesions 21 Recurrence 20 Alabaz et al. Eur J Surg 2000

8. Laparoscopy for Crohn’s Disease Conclusion Better cosmesis Lower incidence of postoperative bowel obstruction Greater than 50% reduction in the disability duration More rapid return to social and sexual interaction Alabaz et al. Eur J Surg 2000

9. Laparoscopy for Crohn’s Disease VariablepLaparoscopyLaparotomy N 2124 Age (years) <0.053139 Male (%) <0.055737 Hospital (days) <0.0535 30-day readmission NS9.60 Morbidity (%) NS14.316.7 Reoperation (%) NS9.60 Direct Cost ($) <0.052,5472,985 Duepree et al. DCR 2002

10. Laparoscopy for Crohn’s Disease Prospective randomized trial January 1994 – March 1998 60 patients Ileal +/- Cecal Crohn’s Disease Milsom et al. DCR 2001

11. Laparoscopy for Crohn’s Disease VariableLaparoscopy ( + )( - ) N3129 Blood loss (mean; ml) * 173133 Operative time (min)* 14085 Incision (cm)* 5.312.7 Milsom et al. DCR 2001 *p<0.0001

12. Laparoscopy for Crohn’s Disease Variable Laparoscopy Analgesic use Morphine sulfate mg/kg/day * ( + )( - ) Day 0 1.31.4 Day 1 0.91.0 Day 2 0.80.6 Day 3 0.50.6 Hospital Stay (days) ** 5.06.0 Milsom et al. DCR 2001 *p>0.3 all days, **p=0.14

13. Laparoscopy for Crohn’s Disease Type of Function Laparoscopic Group (n=31) Conventional Group (n=29) Flatus3*3.3 Bowel Movement44 Milsom et al. DCR 2001 Figures – median (range) days *p=0.07, log-rank test

14. Laparoscopy for Crohn’s Disease Prospective randomized 3-center trial January 2000 – October 2003 60 patients Ileocecal Crohn’s Disease Maartense et al. Ann Surg Feb 2006

15. Laparoscopy for Crohn’s Disease Inclusion Criteria –Elective surgery –Terminal ileum ± cecum disease Exclusion Criteria –Prior median laparotomy –Fixed palpable inflammatory mass –Prior bowel resection Maartense et al. Ann Surg Feb 2006

16. Laparoscopy for Crohn’s Disease VariableLaparoscopy (n=30) Laparotomy (n=30) P Value Gender (m:f) 14:1612:180.602 Age (years) 28310.137 BMI (kg/m²) 21.922.50.994 Steroids 15190.183 5-ASA 770.874 Immunosuppressive medications 5130.017 Maartense et al. Ann Surg Feb 2006 VariableLaparoscopy (n=30) Laparotomy (n=30) P Value Gender (m:f) 14:1612:180.602 Age (years) 28310.137 BMI (kg/m²) 21.922.50.994 Steroids 15190.183 5-ASA 770.874 Immunosuppressive medications 5130.017

17. Laparoscopy for Crohn’s Disease VariableLaparoscopy (n=30) Laparotomy (n=30) P Value Operative time (min) 115900.003 Conversions (n) 3 (10%)- Additional procedures (n) 7 (23%)5 (17%)0.519 Hospital stay (days) 570.008 Complications (pts) 3 (10%)10 (33%)0.028 Maartense et al. Ann Surg Feb 2006

18. Laparoscopy for Crohn’s Disease VariableLaparoscopy (n=11) Laparotomy (n=12) P value Morphine (mg) 0 – 24 (hrs) 28450.15 24 – 48 (hrs) 7190.18 48 – 72 (hrs) 050.68 0 – 72 (hrs) 29620.27 Diet Liquid >1000 ml (days) Normal (days) N=30 2 3.8 N=30 3 5 0.039 0.003 Maartense et al. Ann Surg Feb 2006

19. Laparoscopy for Crohn’s Disease Direct CostsLaparoscopyLaparotomyP Value Operative (Euro) 1,103744<0.001 Overall* (Euro) 6,4128,1960.042 *Relaparotomies,hospital stay, and readmission costs Maartense et al. Ann Surg Feb 2006

20. Laparoscopy for Crohn’s Disease Quality of life in both groupsQuality of life in both groups (SF-36/GIQLI*) Decline in the 1 week Return to baseline after 2 weeks Improvement during the 3-month follow-up compared to preoperative levels (SF-36, p<0.001; GIQLI, p<0.001) * *Gastrointestinal Quality of Life Index No significant differences between laparoscopic and No significant differences between laparoscopic and open groups open groups Maartense et al. Ann Surg Feb 2006

21. Laparoscopy for Recurrent Crohn’s Disease VariablePrimaryRecurrent n4516 Age (years)3032 BMI (kg/m2)19.819.7 Enteric fistula246 Conversion32 Median Time (min)180210 Hospital stay (days)88 Hasegawa et al. Br J Surg 2003

22. Laparoscopy for Complicated Crohn’s Disease 20 Patients – 31 Fistulas Follow-up - 48 (5 – 77) months Morbidity - 16% Conversion - 16% Median hospital stay - 8 days Watanabe et al. DCR 2002

23. Laparoscopy for Complicated Crohn’s Disease 73 resections: 90% - Crohn’s fistulas (10% - diverticular disease) Multiple fistulas – 30% Previous surgery – 39.7% Multiple resections – 12.3% Conversion – 4.1% Overall complication rate – 11% Hospital stay – 5.2 days Regan et al. Surg Endosc 2004

24. Laparoscopy for Crohn’s disease Long-term Outcome Eur J Surg 2000Alabaz et al. Eur J Surg 2000 Mean follow-up – 30 months Bowel obstructions Laparoscopy Laparotomy 8% 31% (p=0.02) DCR 2003Bergamaschi et al. DCR 2003 Follow-up – 5 years 11.1% 35.4% (p=0.02) Recurrence rate Recurrence rate - no difference (27.7% vs. 29.1%)

25. Laparoscopy for Crohn’s Disease Surgical Recurrence Lowney et al DCR Jan 2006Lowney et al DCR Jan 2006 - Retrospective study - Laparoscopic vs. open ileocolic resection - Long-term follow-up (62.9/81.8 months)

26. Laparoscopy for Crohn’s Disease Surgical Recurrence LICR (n=63)OICR (n=50) Age at surgery (yrs) 35.237.1 Disease duration (yrs) 7.27.6 Male/female ratio 26/3717/33 Previous abdominal surgery 711 Preoperative medical treatment None None Steroids Steroids 23 29 17 25 Immunosuppressive agents 1513 Lowney et al, DCR Jan 2006

27. Laparoscopy for Crohn’s Disease Surgical Recurrence LICR (n=63)OICR (n=50)P value Surgical recurrence (%)6 (9.5)12 (24)0.18 Median time to recurrence (mo)59.761.6NS Re-recurrence (%)04 (33)NS Third recurrence01 Postoperative chemoprophylaxis (%) 25 (39)27 (54)0.61 No. of pts with recurrence while taking chemoprophylaxis (%) 4 (67)5 (42)NS Lowney et al, DCR Jan 2006

28. Laparoscopy for Crohn’s Disease PPulmonary function Length of hospital stay Duration of postoperative ileus Cosmesis Postoperative small bowel obstructions Early morbidity Overall hospitalization costs Benefits

29. Laparoscopy and Open Ileocecal Resection for Crohn’s Disease: a Metaanalysis Tilney et al, Surg Endosc 2006 20 studies identified by literature review 15 satisfied inclusion criteria 783 patients 338 (43.2%) underwent laparoscopic resection

30. Laparoscopy and Open Ileocecal Resection for Crohn’s Disease: a Metaanalysis Tilney et al, Surg Endosc 2006 Outcome of Interest No of studies No. of patients OR/WMD95% CI P Value HG chi-square HG p Value Operative outcomes Operative time 1056929.5911.27, 47.900.002128.30<0.001 Postoperative recovery Tolerates oral fluid 2106-2.66-3.44, -1.89<0.0012.150.14 Tolerates oral diet 7340-1.47-2.18, -0.76<0.00116.080.01 Time to first flatus 4191-0.68-1.20, -0.170.0095.910.12 Length of stay 11588-2.97-3.89, -2.04<0.00150.32<0.001

31. Tilney et al, Surg Endosc 2006 Overall conversion rate of 6.8% Operative time was significantly longer in the laparoscopic group Blood loss and complications in the two groups were similar Laparoscopic patients had a significantly shorter time for enteric function recovery and shorter hospital stay Laparoscopy and Open Ileocecal Resection for Crohn’s Disease: a Metaanalysis

32. Tilney et al, Surg Endosc 2006 Laparoscopy and Open Ileocecal Resection for Crohn’s Disease: a Metaanalysis Laparoscopic ileocecal resection is associated with equal adverse events than open surgery Postoperative recovery was enhanced Length of hospital stay was reduced Short incision was associated with improvement in perceived cosmetic results Long-term follow-up evaluation is required Contraindications to laparoscopy for Crohn's disease remain poorly defined

33. Laparoscopy for Crohn’s Disease Cosmesis and Body Image 34 patients, age - 32 (17-52) years –Open ileocolic resection - 11 –Laparoscopic - 11 –No resection - 12 7 day outpatient diary –Crohn’s disease index (CDAI) –Activity index (AI) –Inflammatory bowel disease questionnaire (IBDQ) In clinic Hospital experience questionnaire (HEQ) Photo series questionnaire (PSQ) Dunker et al. Surg Endosc 1998

34. Laparoscopy for Crohn’s Disease Cosmesis and Body Image No differences in CDAI scores AI scores Age Gender Colonic involvement Perianal disease Dunker et al. Surg Endosc 1998

35. Laparoscopy for Crohn’s Disease Cosmesis and Body Image Laparoscopy - significantly better: Body image scale Cosmetic scale Self-confidence after surgery Only 3/34 (8.8%) patients preferred open surgery: (for cosmetic advantage) (for cosmetic advantage) 2/12 - no resection group 1/11 - open group 0/11 - laparoscopic group Dunker et al. Surg Endosc 1998

36. Laparoscopy for Crohn’s Disease Cosmesis and Body Image Even with a hypothetical risk to ureter of 5% during laparoscopy: 21/132 (82%) preferred laparoscopy 7/12 - no resection group 4/11 - open group 10/11 - laparoscopic group 24/32 (75%) would pay more even if the only difference was cosmetic: 10/12 - no resection group 7/10 - open group 7/10 - laparoscopy group Dunker et al. Surg Endosc 1998

37. Laparoscopy for Crohn’s Disease Cost Analysis VariableLaparoscopyLaparotomyP Hospital Stay (days)4.07.00.0001 Direct Costs ($)8,68411,373<0.01 Indirect Costs ($)1,3582,349<0.001 Total Costs ($)9,89513,268<0.001 Young-Fadok et al. Surg Endosc 2001

38. Laparoscopy for Crohn’s Disease Cost Analysis LaparoscopyLaparotomyp Direct Cost ($) 2,5472,985<0.05 Duepree et al. DCR 2002 LaparoscopyLaparotomyp Mean Hospital Charges ($) 9,61417,079<0.05 Shore et al. Arch Surg 2003

39. Laparoscopy for Crohn’s Disease Influence of Experience Group 123p Time interval (months) 241512 Patients (n) 28 *Complex (%) 644664 0.296 **Multiple difficulties (%) 211043 0.005 Mean Operative Time (min) 166129141 0.001 Conversion (%) 32421 0.007 Hospital Stay (days) 5.96.44.9 0.025 Morbidity (%) 71411 0.68 *Fistula, mass, abscess, or previous resection **Any two or more of fistula, mass, abscess, or previous resection Evans et al. DCR 2002

40. Laparoscopy for Crohn’s Disease Influence of Experience DCR 2002Evans et al. DCR 2002 No differences in patients outcome, complication, or conversion rates between early and late experience Am Surg 2002Hamel et al. Am Surg 2002 Plateau after initial experience - no differences in morbidity or conversion rates

41. Laparoscopy for Crohn’s DiseaseCONCLUSIONS FeasibleandsafeFeasible and safe even in cases complicated by fistulas or in patients with previous surgery or recurrent disease DisadvantagesDisadvantages increased operative time

42. Laparoscopy for Crohn’s Disease CONCLUSIONS CONCLUSIONS BenefitsBenefits pulmonary function length of hospital stay duration of postoperative ileus cosmesis postoperative small bowel obstructions early morbidity overall hospitalization costs

43. Laparoscopy for Crohn’s Disease Laparoscopic approach is the preferred approach for patients with Crohn’s disease