1. Current Management of Children with Appendicitis CIPESUR Meeting November 18, 2011 George W. Holcomb, III, M.D., MBA Surgeon-in-Chief Children’s Mercy Hospital Kansas City, Missouri

2. Three Presentations Acute appendicitis 60 - 65% Perforated appendicitis 25 - 30% Perforated appendicitis with well- defined abscess (5-7 day history) 5 - 10%

3. Surgical History for Appendicitis (U.S.) 1990 – 2000 Slow adoption for laparoscopic approach Why –  Relatively small open incision (c/w splenectomy, fundoplication, cholecystectomy)  Many cases done middle of night – OR crews not used to laparoscopy  Benefits were not well appreciated

4. Surgical History for Appendicitis (U.S.) 2000 – 2010 Laparoscopic approach now favored (exclusively used at many centers including CMH) for all conditions: acute, perforated, abscess Why  Operative times improved – closure faster  Significantly fewer wound infections (almost none)  Improved cosmesis, esp if infection develops

5. Laparoscopic Appendectomy Personnel/Port Positions

6. Laparoscopic Appendectomy Technique Window in mesoappendix Vascular stapler across mesoappendix

7. Postoperative Appearance 3 Port Laparoscopic Appendectomy

8. Acute Appendicitis (No Perforation) April 2003 – Nov 2006 609 Pts – laparoscopic appendectomy 3 post-op abscesses (0.49%)

9. Acute Appendicitis Appendiceal Perforation Perforated appendicitis (3 - 5 day hx)  Evacuation/irrigation of purulent material  Wound problems minimized  20% post-op abscess rate

10. Laparoscopic Appendectomy Please use this link if you experience problems viewing the video above.this link

11. Laparoscopic vs Open Appendectomy Perforated Appendicitis Far fewer (almost none) wound infection with laparoscopic approach Allows surgeon to suction/irrigate under direct visualization Less postoperative SBO

12. Adhesive Small Bowel Obstruction After Appendectomy in Children: Comparison Between the Laparoscopic and Open Approach Jan 98-June 05: 1105 Appendectomies-447 Open, 628 Lap. AAP 2006 J Pediatr Surg 42:939-942, 2007

13. Laparoscopic versus Open Appendectomy (1105 Patients) Laparoscopic (n = 628)Open (n = 477)P Value Age (years)11.0 +/- 3.79.2 +/- 5.1p > 0.05 Gender (M/F)355/273301/176p > 0.05 SBO1 (0.2%)7 (1.5%)p = 0.01 Perforated appendicitis186192 Mean time to SBO8 days58 days Median follow-up (years)3.5 (0.8 – 6.5)4.9 (0.9 – 8.3) AAP 2006 J Pediatr Surg 42:939-942, 2007

14. SBO After Perforated Appendicitis (378 Patients) LaparoscopicOpenp value Perforated appendicitis186192 SBO1 (0.5%)6 (3.1%)p = 0.03 AAP 2006 J Pediatr Surg 42:939-942, 2007

15. 2000 – 2010 Questions 1)Do we operate in the middle of the night? 2)Is there an optimal antibiotic regimen for perforated appendicitis? 3)How do we define perforated appendicitis? 4)How do we manage the patient presenting with an abscess? 5)Which is better: SSULS or 3 port appendectomy?

16. 1. When to Operate? Current Practice at CMH Patients identified with appendicitis are booked for laparoscopic appendectomy All receive a dose of rocephin (50mg/kg) and flagyl (30mg/kg) This antibiotic regimen was shown to be most cost effective in PRT If patients present at night, the operations are scheduled for the ‘surgeon of the week’ the next day (8 am or 1 pm start) Appendectomies rarely occur after 10 PM at night

17. Antibiotics Only vs Appendectomy For Non- Perforated Appendicitis Liu K, Ahanchi S, Pisaneschi M, et al. Can acute appendicitis be treated by antibiotics alone? Am Surg 73:1161-1165, 2007 Retrospective comparative study (Level 3 study) in adults found no differences in complications between appendectomy at presentation or antibiotic therapy alone 5% recurrence rate

18. Early Operation Versus Delayed Operation Abou-Nukta F, Bakhos C, Arroyo K, et al. Effects of delaying appendectomy for acute appendicitis for 12 to 24 hours. Arch Surg 141:504-506, 2006 Retrospective comparison in adults (Level 3 study) between operation 12 hours after presentation 308 patients No differences in OR time, complications, % with advanced appendicitis, or length of stay

19. Operation At Presentation Versus The Following Day Yardeni D, Hirschl RB, Drongowski RA, et al: Delayed versus immediate surgery in acute appendicitis: Do we need to operate during the night? J Pediatr Surg 39:464–469, 2004. Retrospective comparison in children (Level 3 study) between operation < 6 hrs after presentation or the following day 126 patients (38 early vs 88 late) No differences in operating time, perforation rate, or complications

20. The remaining four questions can be answered from studies at Children’s Mercy

21. 5 – Expert opinion, or applied principles from physiology, basic science, or other conditions 4 – Case series or poor quality case control and cohort studies 3 – Case control studies 2 – Review of case control or cohort studies with agreement or poor quality randomized trial 1 – Prospective, randomized controlled trials Levels Of Evidence

22. 2. Is There an Optimal Antibiotic Management for Perforated Appendicitis?

23. Prior to 2000, most pediatric centers in the U.S. were treating patients with intraabdominal infections with Ampicillin, Gentamicin and Clindamycin (Triple Antibiotic Therapy) Triple antibx provide good coverage; inexpensive But Gentamicin known to be toxic to hearing and renal function Serum levels recommended for Gentamicin use

24. Same broad spectrum coverage as triples The duo of Ceftriaxone and Metronidazole require no serum levels Ceftriaxone and Metronidazole has been shown to be safe and effective in once/day dosing Daily dosing allows easy transition to outpatient IV therapy, if needed Why Not Use Ceftriaxone/Metronidazole? Advantages

25. Retrospective Review 250 patients w/perforated appendicitis - 1998 - 2004 Those treated with Ceftriaxone/Metronidazole were compared to those treated with triple antibiotic coverage (Ampicillin, Gentamicin, Clindamycin) Retrospective Study (Level 3 study) Parameters included temperature curves for the first 5 post-operative days, abscess rate, length of hospitalization, length of intravenous antibiotic treatment and medication charges CAPS, 2005 J Pediatr Surg 41: 1020-1024, 2006

26. Retrospective Results Retrospective Results Outcomes WBC (x10 3 ) 9.8 +/- 0.5 11.6 +/- 0.4 0.10 LOS (Days) 6.8 +/- 0.47.9 +/- 0.20.03 IV Tx (Days)7.2 +/- 0.5 8.6 +/- 0.4 0.05 Abscess (%) 8.8% 14.2% 0.37 C/MA/G/C P Value CAPS, 2005 J Pediatr Surg 41: 1020-1024, 2006

27. Results Results Temperature Curves 36.5 37 37.5 38 38.5 Admission1 234 5 Post-Operative Days 1 - 5 Tmax (Degrees Celsius) C/M A/G/C * * * * * * P < 0.001 CAPS, 2005 J Pediatr Surg 41: 1020-1024, 2006

28. Results Results Medication Charges Expense of dose ($ dose) = (drug price + dispensing charge ) Expense of course = ($ dose) x (# doses/day) x (days of treatment) CAPS, 2005 J Pediatr Surg 41: 1020-1024, 2006

29. Results Results Medication Charges Ceftriaxone Dose Charge = ( $19.48 + $28.13 ) Expense of Course = ($47.51) x (1 dose/day) x (7 days) = $332 Ampicillin Dose Charge = ( $0.38 + $28.13 ) Expense of Course = ($28.51) x (4 doses/day) x (7 days) = $798 Impact Of Nursing Charges CAPS, 2005 J Pediatr Surg 41: 1020-1024, 2006

30. Results Medication Charges $ of Course C/MA/G/C P Value < 0.0001 $546.01 +/- $29.34 $2494.06 +/- $78.44 CAPS, 2005 J Pediatr Surg 41:1020-1024, 2006.

31. With this information, is there any reason to perform a prospective randomized trial comparing Ceftriaxone/Metronidazole to Triple Antibiotic Therapy (Ampicillin, Gentamicin, Clindamycin) for perforated appendicitis?

32. Why A Prospective, Randomized Trial? Why A Prospective, Randomized Trial? Weaknesses Retrospective Uneven numbers between groups Postoperative care not standardized Recent experience vs historical experience creates bias  Far more laparoscopy in recent cohort (C/M)  (47% in C/M group vs 2% in A/G/C group)  Experience w/laparoscopy improved  Pressures to discharge sooner in recent cohort independent of medication regimen?

33. Prospective Randomized Trial Ceftriaxone/Metronidazole or A/G/C Perforated appendicitis at the time of appendectomy  Hole in the appendix  Visible appendicolith in the abdomen Power 0.8; alpha 0.05; sample size 100 Exclusion Criteria Known allergy to one of the medications

34. Standardized Management All patients receive 5 days IV antibiotics Diet begins after flatus WBC drawn on POD 5 Nl WBC count and tolerating PO’s w/o fever meets discharge criteria If elevated, draw again on POD 7, then if elevated, draw on POD 10 and obtain CT No antibiotics on discharge

35. Results Results Outcomes WBC (x10 3 ) 9.4 +/- 3.9 9.9 +/- 4.4 0.56 0.85 LOS (Days) 6.27 +/- 2.5 6.20 +/- 3.2 0.85 0.48 IV Tx (Days) 6.0 +/- 1.5 6.2 +/- 1.1 0.48 Abscess (%) 20.4% 16.3% 0.79 C/MA/G/C P Value AAP, 2007 J Pediatr Surg 43:79-82, 2007

36. Results Results Medication Charges Total Meds $3370 $3817 0.20 % of Med Charges 4.5% 6.1% <0.001 C/MA/G/C P Value IV Abx $1412 $1940 <0.001 AAP, 2007 J Pediatr Surg 43:981-985, 2008

37. Triples C/M 36.5 37 37.5 38 38.5 39 Admission 12345 Post-Operative Day Max Temeperature (Degrees Celsius ) Results Temperature Curves AAP, 2007 J Pediatr Surg 43:981-985, 2008

38. Conclusions There is no difference in infectious complications, recovery or defervescence after perforated appendicitis between Ceftriaxone/Metronidazole and Triples (A/G/C) Ceftriaxone/Metronidazole is more cost- effective than standard triple antibiotic therapy AAP, 2007 J Pediatr Surg 43:981-985, 2008

39. The literature is replete with retrospective studies regarding perforated appendicitis All of these studies fail to strictly define perforation  Dependent on surgeon’s definition  “Gangrenous”, “suppurative”, “perforated” Therefore, the conclusions from these retrospective reports must be approached cautiously 3.How Do We Define Perforated Appendicitis?

40. J Pediatr Surg 43:2242-2245, 2008 J Pediatr Surg 43:2242-2245, 2008

41. Post-operative Antibiotic Regimen For Perforated Appendicitis In Children: A Prospective Randomized Trial April 2005 - November 2006 100 patients To ensure accurate data, the two groups had to be equal and a definition had to be created

42. Visible appendicolith Hole in appendix Definition of Perforation Used in Prospective Randomized Trial

43. Hypothesis A correct definition of perforation (DOP) is important because  Provides us with the information to safely and efficiently treat patients  Allows us to better identify which patients are at risk for developing postoperative complications If our definition of perforation was correct  There should be no increase in abscess rate in the cohort of patients treated as non-perforated appendicitis after the definition was used If our definition of perforation was incorrect  There should be an increase in abscess rate in the cohort of patients treated as non-perforated appendicitis after the definition was used (b/c of under-treatment)

44. Results Outcomes NON- Perforated Prior DOP (n=292) After DOP (n=388) Abscess rate1.7%0.8% LOS (days)1.9 +/- 1.31.5 +/- 1.5 Perforated Prior DOP (n=131) After DOP (n=161) Abscess rate14.0%18% LOS (days)9.4 +/- 4.27.4 +/- 8.8 PAPS 2008 J Pediatr Surg 43:2242-2245, 2008 J Pediatr Surg 43:2242-2245, 2008

45. Conclusions Our strict DOP (either a visible hole in the appendix or appendicolith in the abdomen) has been shown to be safe  No increase in abscess rate for non-perforated patients  No detectable risk of under treating patients defined as non- perforated This DOP will improve overall care for children with appendicitis  Eliminate unnecessary antibiotic treatment  Improve cost management  Simplify treatment protocols  Improve the integrity of clinical data  Allow for ongoing clinical research PAPS 2008 J Pediatr Surg 43:2242-2245, 2008

46. 4.How do we manage the child presenting with an abscess due to ruptured appendicitis?

47. Perforated Appendicitis Presenting With Abscess Open operation for abscess is difficult Percutaneous drainage has been described and applied Laparoscopy is being used to treat perforated appendicitis and abscess Which is better? History

48. Perforated Appendicitis with Abscess 1)5 - 7 day history 2)Dehydrated – needs IVF 3)Percutaneous drainage (interventional radiology) 4)PICC line - antibiotics 5)Discharge day 3-5 if stable 6)Antibiotics con’t 10 - 14 days at home 7)Return 8-10 wk. for interval appendectomy (to prevent recurrent appendicitis) - overnight hospitalization

49. Retrospective Experience with Interval Appendectomy 52 patients – 2000-2006 Total hospital days = 7.0 +/- 3.9 Total healthcare visits = 7.6 +/- 2.8 Total number of CT scans = 3.5 +/- 2.0 Recurrent Abscess = 10 pts (19.2%) AAP, 2007 J Pediatr Surg 43:981-985, 2008

50. Perforated Appendicitis with Abscess Perforated Appendicitis with Abscess Prospective Trial Drainable abscess OR for laparoscopic appendectomy vs percutaneous drainage as initial management Drain groups undergoes laparoscopic appendectomy at 10 weeks. Quality of life surveys at admission, at 2 weeks and at 12 weeks Pilot study – 40 patients APSA 2009 J Pediatr Surg 45:236-240, 2010

51. Initial Non-Op Mgmt vs Lap Appendectomy in Children Presenting with an Abscess APSA 2009 J Pediatr Surg 45:236-240, 2010 Patient Characteristics at the Time of Admission Initial operation (n=20) Initial nonoperative management (n=20) P Age (y)10.1 ± 4.28.8 ± 4.2.31 Weight (kg)37.0 ± 16.237.1 ± 20.8.98 Body mass index (kg/cm 2 )18.0 ± 4.519.5 ± 5.5.39 White blood cell count17.4 ± 6.616.9 ± 6.8.84 Maximum temperature37.8 ± 1.037.7 ± 0.9.95 Maximum axial area of abscess (cm 2 ) 29.2 ± 29.726.2 ± 21.1.75 Values are expressed as mean ± SD

52. Initial Non-Op Mgmt vs Lap Appendectomy in Children Presenting with an Abscess APSA 2009 J Pediatr Surg 45:236-240, 2010 Outcomes Comparing Initial Operation and Initial Abscess Drainage Followed by Interval Appendectomy Initial operation (n = 20) Initial nonoperative management (n = 20) P Operation time (min)62.1 ± 38.742.0 ± 45.5.06 Total length of hospitalization (d)6.5 ± 3.86.7 ± 6.6.92 Recurrent abscess after initial treatment (%) 20%25%1.0 Doses of narcotics9.7 ± 4.07.1 ± 15.8.47 Total health care visits2.8 ± 1.14.1 ± 1.0<.001 No. of CT scans1.5 ± 0.72.1 ± 1.1.04 Total charges$44,195 ± $19,384$41,687 ± $18,483.68 Values are expressed as mean ± SD, unless otherwise indicated

53. Prospective Randomized Trial Conclusion – There is no difference b/w initial laparoscopic operation vs initial non-operative management followed by laparoscopic interval appendectomy Management can be determined by the surgeon’s preference and experience APSA 2009 J Pediatr Surg 45:236-240, 2010

54. 5.Is there an advantage performing the laparoscopic appendectomy through a single umbilical incision?

55. SSULS Appendectomy

56. Please use this link if you experience problems viewing the video above.this link

57. Postoperative Appearance

58. Prospective Randomized Trial 360 total patients Acute non-perforated appendicitis August 09 – November 10 Primary outcome variable – postoperative wound infection Standardized pre and postoperative management Quality of life surveys at 6 weeks and 6 months Single Umbilical Incision vs 3-Port Laparoscopic Appendectomy

59. Patient Characteristics at Operation Single Incision (N=180) 3-Port (N=180) P-value Age (yrs)11.05 ± 3.4711.04 ± 3.410.98 Weight (kg)42.7 ± 18.542.5 ± 17.40.90 Gender (% male)54.4%51.1%0.53 Leukocyte count14.7 ± 5.214.6 ± 5.40.89 American Surgical Assn – 2011 Ann Surg 254:586-590, 2011

60. Outcome Data Single Incision (N=180) 3-Port (N=180) P- value Wound Infection3.3%1.7%0.50 Operative Time (mins)35.2 ± 14.529.8 ± 11.6<0.001 Postoperative Length of Stay (hours) 22.7 ± 6.222.2 ± 6.80.44 Hospital Charges ($)17.6K ± 4.0K16.5 ± 3.8K0.005 American Surgical Assn – 2011 Ann Surg 254:586-590, 2011

61. Summary There have been significant changes in the surgical management of appendicitis These changes have revolved around timing of surgery and the almost exclusive use of the laparoscopic approach Unclear if appendicitis will be a surgical disease in the future

62. QUESTIONS www.cmhclinicaltrials.com www.cmhmis.com