Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

CONTEXT: - Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. OBJECTIVES: - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. DESIGN: - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical records from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. RESULTS: - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. CONCLUSIONS: - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

Management of adverse events associated with idelalisib treatment: expert panel opinion.

Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel's recommendations for identification and management of idelalisib treatment-emergent diarrhea or colitis as well as a discussion of transaminitis and pneumonitis. For idelalisib-related diarrhea or colitis (including unresolved grade 2 and grade ≥ 3), after exclusion of infectious causes, the panel recommends individualized treatment with budesonide or oral or intravenous steroid therapy.

Inflammatory bowel disease following solid organ transplantation.

Inflammatory bowel disease (IBD) is a T cell driven inflammatory condition of the gut. Following solid organ transplantation (SOT), de novo IBD has been reported despite anti-T cell therapy for the prevention of organ rejection. This paradox is illustrated with a case report, highlighting the difficult diagnostic criteria, the potential role of Damage or Pathogen Associated Molecular Pattern Molecules [DAMPs and PAMPs] that drives aspects of ongoing inflammation within the transplanted organ as well as the intestine, and the therapeutic strategies applied. Recurrent IBD is more common than de novo IBD following transplantation, with cumulative risks ten years after orthotopic liver transplantation of 70% and 30%, respectively. Furthermore, the annual incidence of de novo IBD following solid organ transplantation has been estimated to be 206 cases/100,000 or ten times the expected incidence of IBD in the general population (approximately 20 cases/100,000). The association of IBD with other autoimmune conditions such as primary sclerosing cholangitis and autoimmune hepatitis, both common indications for liver transplantation, may play a contributory role, particularly in view of the observation that IBD is more common following liver transplant than other solid organ transplants. Recurrent IBD following transplant appears to run a more aggressive course than de novo IBD, with a higher proportion requiring colectomy for medically refractory disease. Risk factors that have been associated with development of post-transplant IBD include acute CMV infection and the use of tacrolimus.

Using capsule endoscopy to identify GI tract lesions in cirrhotic patients with portal hypertension and chronic anemia.

GOALS: We aimed to evaluate the ability of capsule endoscopy (CE) to detect small intestine (SI) lesions, especially SI varices, in patients with intrahepatic cirrhosis, portal hypertension (PHTN), and chronic anemia. BACKGROUND: Gastroesophageal variceal bleeding is a well-recognized complication of cirrhosis and PHTN, yet methods of identifying lesions in the SI that may contribute to covert bleeding and anemia, such as small bowel enteroscopy and angiography, are invasive and may be inadequate. STUDY: In this observational pilot study, 19 consecutive patients presenting to a tertiary care, liver transplantation referral center with cirrhosis, PHTN, and chronic anemia after obliterative esophageal variceal therapy were evaluated with wireless CE using the GIVEN Pillcam SB M2A capsule. Two independent and blinded examiners reviewed the CE examinations. RESULTS: SI varices were identified in 15.8% (3/19) of patients. Other PHTN-related findings included portal hypertensive gastropathy (13/19, 68.4%), portal hypertensive enteropathy (12/19, 63.1%), and portal hypertensive colopathy (3/19, 15.8%). Two patients had nonbleeding esophageal varices (2/19, 10.5%). A potential source of gastrointestinal blood loss was identified in 89.5% (17/19) of patients. Active bleeding sites were identified in 15.8% (3/19). CONCLUSIONS: CE can identify potential bleeding sources and could have diagnostic utility in patients with end-stage liver disease and chronic anemia after obliterative esophageal variceal therapy.