Kourosh goudarzipour Jan-2014

 Altinel E, et al. Typhlitis in Acute Childhood Leukemia. Med Princ Pract 2012; 21:  H Abdul-Jabar, R Clough, A ChopadaManagement of Neutropenic ColitisThe Internet Journal of Surgery,vol15,n:1,2007.Management of Neutropenic ColitisThe Internet Journal of Surgery  M. Beth McCarville, M.D. Typhlitis in Childhood Cancer, American Cancer Society,2005.  Dhanya Mullassery a,, Abdulgader Bader b, Anna J. Battersby, Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients—experience in a tertiary pediatric surgical center in the United Kingdom, Journal of Pediatric Surgery (2009) 44, 381–385

Typhlitis Basics: Causes of Typhlitis Pathophysiology Typhlitis Presentation Typhlitis Increased Risk Factors Imaging for Typhlitis Therapy for Typhlitis

 Necrotizing inflammation of the colon, cecum, and / or terminal part of the ileum.  Also known as “Neutropenic colitis” (although the patient does not have to be strictly neutropenic).  Associated with:  Underlying Malignancy  Intensive Chemotherapy  Severe Neutropenia

 Incidence : 0.35% to 10% of children with malignancies (depending on the study).  In recent years, with the use of more intensive chemotherapy regimens, there has been an increase in incidence of typhlitis.

 Suspected culprits:  Drug-induced GI ulcerations  Neutropenia leading to invasive bacteria related mucosa damage  Sepsis-induced hypotension leading to bowel ischemia  Combination of all…

 Although the exact etiology and progression are clearly unknown, profound neutropenia appears to be the common dominator.  Granulocytopenia resulting from marrow infiltration, aplasia or myelosupression causes a major deficit in the key internal host defence mechanism against intestinal mucosal injury and bacterial invasion.

 The pathological process appears to have a predisposition for the terminal ileum, appendix and caecum, hence its alternative nomenclature. Many factors have been described that may potentially play a role in the development of this condition and include the following:

 Mucosal injury caused by chemo-therapeutic agents, which can alter the normal mucosa leading to local ulceration and ischaemia. Caecal distension, whether primary or secondary to cytotoxic drug therapy, may further compromise the blood supply and lead to local ulceration and ischaemia.

 The use of antibiotics and steroids may also contribute to an altered enteric bacterial flora and fungal overgrowth.  Bacterial invasion of the damaged bowel wall may result in transmural inflammation leading to perforation and generalised peritonitis.

 Cytosine Arabinoside which are used in combination therapy in the treatment of haematological malignancies appear to be the most potent and toxic combination in causing the spectrum of damage.

 bacteria and fungi: E. coli, Klebsiella, Pseudomonas, Enterococcus and Candida species.

 The sudden onset of abdominal pain (often right lower quadrant), fever (temperature >38ºC) and diarrhoea are often the hallmarks of presentation of a patient with neutropenic colitis ( usually 7-10 days after myelosuppressive chemotherapy).  If the initial symptoms are followed by peritonitis, haemodynamic instability and septic shock, the prognosis is poor

 mass palpable in the right iliac fossa or the lower abdomen;  Rapid progression to fulminant septicaemia may precede the development of any abdominal signs.  The diagnosis is difficult and a significant number of patients are only diagnosed at post mortem.  A high index of suspicion of the possibility of neutropenic colitis in immunosupressed patients is most important in timely diagnosis

 the diagnosis was confirmed using imaging when only 2 or more clinical features were present.  This is consistent with the reported 15% of patients with suspected typhlitis on imaging (bowel wall thickness ≥ 0.30 on US) who did not have one of more of the typical clinical features (abdominal pain, fever, and neutropenia).

 Appendicitis  cholecystitis  pancreatitis  C. difficile colitis  hepatic abscess  other bacterial viral/fungal/parasitic causes of colitis  GVHD:in patients with HSCT

 Ideal imaging modality is still debated… and likely dependent upon your institutional resources.  Abdominal X-Ray  May show small bowel obstruction  May show fluid-filled cecum  More useful to look for Free-air and Air-fluid levels.  Abdominal CT  +: can help differentiate other abdominal pathology.  _: Radiation, Bowel Wall thickness does not correlate with severity of typhlitis. less well tolerated by sick children  Abdominal U/S  +: no Radiation. Pt’s tolerate well. The degree of Bowel Wall Thickening has been correlated with severity of disease.  _: Operator dependent (so need good institutional experience). Need to evaluate the length of the colon… not just RLQ.

 Generally, conservative management is successful, when detected early in the course of the condition.  NPO  IVF  Broad Spectrum Antibiotics (ex:…) Ceftazidime Meropenem Pip/Tazo Metronidazole

 Surgical intervention should be used for bowel perforation, persistent GIB, or clinical deterioration despite optimal medical management.

 The diagnosis of typhlitis is essentially clinical and may be supported by evidence provided by imaging.  Medical treatment is usually successful, and therefore, surgical intervention should be reserved for clear evidence of peritonitis or to rule out other surgical pathologic condition.