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Colo-gastric Fistula as an Uncommon Complication of Crohn’s Disease Molly Stone, MD September 28, 2019 Background

- Crohn’s Disease (CD): a transmural inflammatory process which often gives rise to sinus tracts and eventually fistulization into adjacent serosa. - Fistulizing disease is a common complication of CD - Risk increases with longer disease duration - Prevalence of 15% in childhood; up to 50% at 20 yrs from dx - Fistulas most commonly form in perianal region - Intra-abdominal fistula develop in approximately 30% of patients. Common Sites of Fistulas

Torres. The Lancet. 2017. Gastrocolic Fistula

- First described in 1775, first case related to Crohn’s Disease reported in 1948 - Most commonly seen with peptic ulcer disease, cases also noted in gastric and colon cancers in addition to Crohn’s. - Classic Triad: diarrhea, weight loss, feculent emesis - Only present in 30% of cases - Presence of feculent emesis helps to distinguish gastrocolic from more distal entero-enteric fistulas Epidemiology

- Rare complication noted in only 0.6% of CD pt - Youngest reported case in a 13 yo pt who had CD for 3 yrs, however most pts range 25-60 with disease duration >10 yrs - M=F - Predisposing factors: Ileal disease and prior ileocolic anastomoses Pathogenesis

- Most form from mid- to distal transverse colon to the greater curvature of the stomach - Initiate from active area of colitis - Multiple cases with evidence of proximal disease on resection implying gastric to colic or bidirectional formation

Greenstein, Diseases of Colon and . 1989. Evaluation

- Symptoms: - Nausea, feculent halitosis, steatorrhea and weight loss - Exam: - Generalized abdominal tenderness and distension, dehydration, and signs of inflammatory response - Labs: - Non-specific (including hypoalbuminemia, electrolyte abnormalities, elevated ESR/CRP and leukocytosis) Diagnosis

- Frequently noted on CT and MRI done for acute IBD flares and/or infectious symptoms - Barium enema is the test of choice, sensitivity 85-95% - Endoscopy not often used for diagnosis but helpful for pre-

operative planning Rout. Indian Journal of Surgical Oncology, 2013 Case 1 52yo man was referred to IBD clinic after severe inflammation with pseudopolyps incidentally noted on screening colonoscopy. - Upon questioning, reported a history of peri-rectal 10 yrs prior requiring I &D - Historically, 4-5 loose stools daily, crampy abdominal pain for the last several years but never sought further evaluation - Labs on initial IBD visit notable for ESR 74 CRP 6.11, fecal calprotectin 179, Alb 3.4, Iron sat 8, folate 5.3 Therapy plan: Adalimumab monotherapy for moderate CD - Developed persistent abdominal pain after completing steroid taper - Azathioprine added with lab monitoring for safe uptitration Symptoms again initially improved and then worsened at which time labs drawn and EGD performed.

Ex-lap with right hemicolectomy, primary repair of colo-gastric fistula - Duodenopancreatic fistula found at the time of , repaired. JP drain placed in anticipation of pancreatic leak. - Fluid amylase initially 858, down to 385 with drainage. JP removed on POD#13. - Once cleared by surgery from post-op infectious risk, resumed dual biologic therapy. - Repeat dual endoscopy approximately 3 months later demonstrated deep remission. Case 2 53yo woman with 30 year history of penetrating CD complicated by chronic asymptomatic draining perianal fistula - Presented to OSH with acute onset abdominal pain with nausea and for approximately 3 days. - Off maintenance therapy for five years. Started Ustekinumab four weeks prior due to increased symptoms over preceding six months.

Medications were changed to: - Azathioprine 50 mg - Prednisone taper - Infliximab induction with 10 mg/kg

She continued Infliximab induction with second 10 mg/kg dose followed by right hemicolectomy with fistula takedown and primary repair. - Resumed Infliximab and Azathioprine once cleared from post-operative infectious risk - Resolution of symptoms and imaging resolution within two months. Fistula Management

- Defines phenotype as penetrating rather than just inflammatoryAntibiotics - Treatment of underlying disease - best data for IFX - Extensive disease - bowel rest and TPN vs surgical diversion - More common in perianal fistulizing disease - Although reflux of colonic contents into gastric mucosa can have deleterious effects on the tissue (bacterial overgrowth, ), repair is not emergent. Medical Management

- Antibiotics - Few cases have been reported with good outcomes of colo- gastric following medical-only therapy - 6-MP, sulfasalazine and systemic steroid (1985) - No consistent evidence for MTX or IV cyclosporine in studies Role of Biologic Therapy - Anti-TNF therapy: - Shown to be effective in induction and maintenance of perianal fistula closure with effects enhanced by concurrent thiopurine use - Infliximab alone has been used to successfully close two enterocutaneous fistulas and one duodenopancreatic fistula - Post-hoc data of UST trials support its use Surgical Intervention - Common procedures: - Diversion: definitive diverting ostomy or exclusion bypass - Staged: Temporary followed by primary closure and - Resection with fistula repair: ileocolonic resection with simple fistula closure or complex gastric reconstruction - Newer techniques include laparoscopic repair with stapling of fistula tract Outcomes

- The vast majority of patients do well following surgical and medical management of fistula without significant sequelae - Key to long-term management and prevention of recurrence is induction and maintenance of clinical and histologic remission of the underlying Crohn’s Disease. References - Spirit M, Sachar DB, Greenstein AJ. Symptomatic differentiation of duodenal from gastric fistulas in Crohn’s disease. American Journal of Gastroenterology. 1990;85(4):455-8. - Gidvani V, Mizell L. colo-gastric fistula in pediatric Crohn’s disease. Journal of Pediatric Gastroenterology, Hepatology and Nutrition. 1997;25(3):347-9. - Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis, and multidisciplinary treatment of perianal fistulising Crohn’s Disease. Gut. 2014;63:1381-1392. - Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s Disease. The Lancet. 2017; 389(10080):1741-1755. - Gisbert JP, Gomollon F. Timing of surgery in Crohn’s disease: A key issue in the management. World Journal of Gastroenterology. 2008;14(36):5532-5539. - Zuiki T, Meguro Y, Kumano H, et al. Successful Management of a Colo-Duodenal Fistula in a Patient with Crohn’s Disease Using a Double Lumen Gastro-Jejunostomy Tube.2014; 8(2); 162-8. - Khanna, M.P. and P.H. Gordon, colo-gastric fistulization in Crohn's disease: a case report and a review of the literature. Canadian Journal of Surgery. 2000; 43(1): 53- 6. - Perez-Tamayo A, Congreve DP, Bartolome JS, et al. Perforated Benign colo-gastric Fistula. JAMA Surgery. 1983;118(9):1105. - Pachiadakis I, Nakos A, Tatsi P, et al. Simultaneous occurrence of hyperthyroidism and fistulizing Crohn’s disease complicated with intra-abdominal fistulas and abscess: a case report and review of the literature. Cases Journal. 2009; 2:8541. - Jacobson IM, Schapiro RH, and Warshaw AL. Gastric and Duodenal Fistulas in Crohn’s Disease. Gastroenterology. 1985;89:1347-52. - Sheen E, Huang RJ, Triadafilopoulos G. Two Evils: colo-gastric Fistula and Heart Failure. Digestive Disease Science. 2014; 59:928-32. - Pichney LS, Fantry GT, Graham SM. colo-gastric and Duodenocolic Fistulas in Crohn’s Disease. Journal of Clinical Gastroenterology. 1992; 15(3):205-11. - Nagaj S, Nagayoshi K, Sadakari Y, et al. Application of a linear stapler to the laparoscopic treatment of colo-gastric fistula in patients with Crohn’s disease. Techniques in Coloproctology. 2018;22:981-984. - Greenstein AJ, Present DH, Sachar DB, et al. Gastric Fistulas in Crohn’s Disease: Report of Cases. Diseases of the Colon and Rectum. 1989; 32:888-92. - Adegbola SO, Sahnan K, Tozer PJ, et al. Review of local injection of anti-TNF for perianal fistulising Crohn’s disease. International Journal of Colorectal Disease. 2017; 32:1539-44. - Present DH, Rutgeerts P, Targan S, et al. Infliximab for the Treatment of Fistulas in Patients with Crohn’s Disease. New England Journal of Medicine. 1999;340:1398- 1405. - Pajares, JA, Hernandez L, Menchen P, and Menchen L. Duodenopancreatic fistula complicating upper gastrointestinal Crohn’s disease: successful treatment with infliximab. American Journal of Gastroenterology. 2009; 104(7):1863-4. Thank you!