Disclosure of Affiliations Immunomodulators and Complications of - PowerPoint PPT Presentation

Disclosure of Affiliations Immunomodulators and Complications of Surgery for None Inflammatory Bowel Disease Thomas E. Read, MD, FACS, FASCRS Professor of Surgery Tufts University School of Medicine Senior Staff Surgeon and Program Director Department of Colon and Rectal Surgery Lahey Hospital and Medical Center Burlington, MA, USA Medicines and Surgery for IBD The Way We Hope It Goes Cases: Sweet and Not So Sweet • Blame the drugs when things go wrong? History Inflammatory cytokines Effect of anti-TNFs on treatment philosophy Effect of anti-TNFs on surgical complications 1

Not So Sweet Case Not so sweet case Recurrent ileal Crohn’s with intra-abdominal abscess Leak • On biologics, steroids for recent flare One week prior at outside hospital: • Ileocolic resection, drainage of abscess, takedown of ileosigmoid fistula Surgeon calls me Sat. night • Patient in shock • Requesting transfer Not So Sweet Case Medicines and Surgery for IBD OR: Leak Cases: Sweet and Not So Sweet History • Drains • The story of Crohn (‘s) • Diverting ileostomy proximal to ileocolic anastomosis • Surgery and Medicine for IBD • When to operate Inflammatory cytokines Blame the drugs? Effect of anti-TNFs on treatment philosophy Effect of anti-TNFs on surgical complications 2

History of Crohn’s The story of Crohn AA Berg (Chief of Surgery, Mt. Sinai) recognizes the disease and instructs his protégées • (Leon Ginzburg and Gordon D. Oppenheimer) to investigate his 14 cases Ginzberg collects data on 12 patients • Burrill B. Crohn (GI) collects data on 2 patients, appropriates Ginzburg’s data, • presents series to AMA Ginzburg and Oppenheimer present data from a larger series of patients to the American • Gastroenterological Association 2 weeks later. Daniel Present, MD personal communication Nov 2004 • AH Aufses. The History of Crohn’s Disease. Surg Clin N Am. 2001. 81 (1): 1-10. • The story of Crohn The story of Crohn Ginzburg brings charges against Crohn to Mt Sinai medical board and wins case • • AA Berg ultimately publishes his series Ginzburg’s only victory is having his name appear on the paper, in which authors • are listed in alphabetical order AA Berg. An operative procedure for right-sided ulcerative colitis. Berg declines to have his name on manuscript because it has been his tradition that • he only publish manuscripts with his name alone. Ann Surg. 173: 91-96, 1936. Daniel Present, MD personal communication Nov 2004 • AH Aufses. The History of Crohn’s Disease. Surg Clin N Am. 2001. 81 (1): 1-10. • 3

The story of Crohn History of IBD Treatment Crohn: gastroenterologist in NY Surgery • Ginzburg: chief of surgery, Beth Israel Medical Center, NY • • Mainstay of therapy for decades Oppenheimer: chief of urology, Mt. Sinai • • Ileal Crohn’s • 1 st stage: Ileocolic bypass • 2 nd stage: Ileocolic resection • Ulcerative colitis • Ileostomy and cecostomy 1982. Courtesy Daniel Present, MD Ginzburg Crohn Present History of IBD Treatment New Surgical Philosophy: IBD Medical Treatment When to operate Steroids • • Obstruction Local or systemic • 5-ASA compounds • • Perforation Sulfasalazine (Azulfidine), Olsalazine (Asacol), Mesalamine (Asacol, Pentasa, Rowasa) • • Bleeding Antibiotics • Metronidazole (Flagyl) • • Failure of medical therapy Immunosuppresives • • Prevention/treatment of 6-Mercaptopurine (6-MP), Immuran • colorectal cancer Cytokine antagonists • Anti-TNF Ab, rh-IL-10, ICAM-1 antisense oligonucleotide (ISIS 2302), rhIL-11 • GMCSF • Surgery as a last resort 4

New Surgical Philosophy: Crohn’s Medicines and Surgery for IBD Cases: Sweet and Not So Sweet Inflammatory component History • Medical management • The story of Crohn (‘s) • Operate when medical • Surgery and Medicine for IBD management fails to control symptoms • When to operate Inflammatory cytokines Effect of anti-TNFs on treatment philosophy Fibrotic component Effect of anti-TNFs on surgical complications • If symptomatic, operate 5

Initial insult in Inflammatory Bowel Disease Initial insult in Inflammatory Bowel Disease History of IBD Treatment Anti-TNF agents Medical Treatment Infliximab (Remicade) Steroids • Local or systemic • Adalimumab (Humira) 5-ASA compounds • Sulfasalazine (Azulfidine), Olsalazine (Asacol), Mesalamine (Asacol, Pentasa, Rowasa) • Certolizumab (Cimzia) Antibiotics • Metronidazole (Flagyl) • Immunosuppresives • 6-Mercaptopurine (6-MP), Immuran • Cytokine antagonists • Anti-TNF Ab, rh-IL-10, ICAM-1 antisense oligonucleotide (ISIS 2302), rhIL-11 • GMCSF • 6

Sepsis Research Initial insult in Infliximab for fistulizing Crohn’s Inflammatory Bowel Disease “Reduction” in fistula activity > 50% Infliximab 5mg/kg 68% • Placebo 26% • “Temporary” closure of fistula Infliximab 5mg/kg 55% • Placebo 13% • Median duration until fistula re-appeared: 3 months • N Engl J Med. 1999 340(18):1398-405. • 7

Perianal Crohn’s Disease Perineal Crohn’s Disease Perianal Disease--”Watering Can Perineum” Untreated Fistulous Disease • 33 yo F refused medical care • Bacon poultice Infliximab for fistulizing Crohn’s Medicines and Surgery for IBD Cases: Sweet and Not So Sweet History • The story of Crohn (‘s) • Surgery and Medicine for IBD • When to operate Inflammatory cytokines Effect of anti-TNFs on treatment philosophy Long term fistula healing (54 weeks) • Infliximab 5mg/kg + maintenance infliximab 36% • Too much medication? • Infliximab 5mg/kg + no maintenance 19% Effect of anti-TNFs on surgical complications Putting it all together N Engl J Med. 2004. 350(9):876-85. 8

Management of IBD Management of IBD The Present The Past Steroids • • Local or systemic • Steroids 5-ASA compounds • • 5-ASA • Sulfasalazine (Azulfidine), Olsalazine (Asacol), Mesalamine (Asacol, Pentasa, Rowasa) Metronidazole (Flagyl) • 6-Mercaptopurine (6-MP), Immuran • • Surgery Cytokine antagonists • • Anti-TNF Ab (Infliximab), rh-IL-10, ICAM-1 antisense oligonucleotide (ISIS 2302), rhIL-11 GMCSF • Others • Surgery • Too Much Medication? Ileal Crohn’s 27 year old man: Ileal fistula through sigmoid mesocolon into left psoas to left flank and left groin “Do not let your patient lose their colon until you have tried all the medications.” --Daniel Present, MD Fistula UCSF IBD conference Psoas abscess Nov. 6, 2004 Terminal ileum Flank abscess 9

Ileal Crohn’s Ileal Crohn’s: Too Much Medication Treated with 5-ASA, steroids, 6-MP, infliximab for 18 months • Chronic septic state Ileal-psoas-cutaneous fistulas • Weight loss, lethargy • Forced to quit work • Treatment • Persistent pus drainage from left flank and left groin • Drain abscesses • Control fistulas • TPN Flank abscess Inguinal fistula • Antibiotics Ileal Crohn’s: Too much medication? Ileal Crohn’s with fistula Follow up at 6 months OR • Patient happy • Doing well • Severe ileal disease with fistula through sigmoid mesocolon into • Energy improved left psoas and into left flank and groin • No sepsis • Colon intrinsically normal • Back to work • Fistulas healed • Ileocolic resection, • Off steroids takedown of fistula, • Maintenance 5-ASA only primary anastomosis Wife unhappy • Sigmoid colon spared • Husband has “too much energy” 10

Too Much Medication? Social Problems in the Sandbox of Life Bad terminology Mathematics • It is not a “failure” for an IBD patient to require surgery Gastroenterology Surgery • It is better to operate prior to Medical “saves” Medical “failures” debilitation and malnutrition, than to Total n ? Total force the patient to try every new drug available We rarely see the Failures are the problem successes of of the surgeon medical therapy Perioperative Complications Medicines and Surgery for IBD Cases: Sweet and Not So Sweet Associated with History • Steroids Inflammatory cytokines • Immunosuppressives Effect of anti-TNFs on treatment philosophy • 6-MP, Imuran Effect of anti-TNFs on surgical complications • Single center data • Meta-analysis • ?anti-TNF agents? Putting it all together 11

Single center data: Toronto Complications No difference in outcomes Gut. 2013. 62: 387-394 Time Interval from Last Dose Readmissions Cedar-Sinai, LA No difference in outcomes 12

Readmissions Meta-analysis: Complications Increase as number of medications increase Total Complications Complications: Meta-analysis Increased with anti-TNFs 13

Infectious Complications Non-Infectious Complications Increase with anti-TNFs Increase with anti-TNFs Total Complications Problems with the Data Increase with anti-TNFs 14