Belgian Recommendations for Analytical Verification and Validation of Immunohistochemical Tests in Laboratories of Anatomic Pathology.

Analytical verification and validation of immunohistochemical (IHC) tests and their equipment are common practices for today's anatomic pathology laboratories. Few references or guidelines are available on how this should be performed. The study of Sciensano (the Belgian national competent authority regarding licensing of medical laboratories) performed in 2016, demonstrated a significant interlaboratory variation in validation procedures of IHC tests among Belgian laboratories. These results suggest the unavailability of practical information on the approach to the verification and validation of these tests. The existing Belgian Practice Guideline for the implementation of a quality management system in anatomic pathology laboratories has been reviewed to meet this demand and, in addition, to prepare the laboratories for the EU-IVD revised regulations (IVDR). This paper describes Belgian recommendations for the verification and validation of IHC tests before implementation, for ongoing validation, and for revalidation. For each type of test (according to the IVDR classification and the origin) and its intended use (purpose), it addresses how to perform analytical verification/validation by recommending: (1) the number of cases in the validation set, (2) the performance characteristics to be evaluated, (3) the objective acceptance criteria, (4) the evaluation method for the obtained results, and (5) how and when to revalidate. A literature study and a risk analysis taking into account the majority of variables regarding verification/validation of methods have been performed, resulting in an expert consensus recommendation that is a compromise among achievability, affordability, and patient safety. This new consensus recommendation has been incorporated in the aforementioned ISO 15189:2012-based Practice Guideline.

Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea.

BACKGROUND: Diarrhea is the most frequently reported adverse event in mycophenolate mofetil (MMF)-treated transplant patients. The aim of this study was to explore the gastrointestinal tract in MMF-treated renal transplant recipients with persistent afebrile diarrhea to characterize its nature and etiology. METHODS: Renal transplant recipients with persistent afebrile diarrhea (daily fecal output >200 g) were prospectively investigated for infections, morphologic, and functional (gastrointestinal motility and intestinal absorptive capacity) integrity of the gastrointestinal tract; 26 patients met the inclusion criteria. RESULTS: All but one patient had an erosive enterocolitis. Seventy percent of the patients had malabsorption of nutrients, contributing to the diarrhea. In +/-60%, an infectious origin was demonstrated and successfully treated with antimicrobial agents without changes in immunosuppressive regimen. In +/-40%, no infection occurred, but a Crohn's disease-like pattern of inflammation was noted. These patients also had a less pronounced bile-acid malabsorption but a significant faster colonic transit time, correlating with the trough level of mycophenolic acid (MPA). Cessation of MMF, however, was associated with allograft rejection in one third of these patients. CONCLUSIONS: Persistent afebrile diarrhea in renal transplant recipients is characterized by erosive enterocolitis, which is of infectious origin in +/-60%. In +/-40%, a Crohn's disease-like (entero-)colitis was present. Because reduction or cessation of MMF was the only effective therapy, MPA or one of its metabolites may be suggested as a possible cause. However, reduction or cessation of MMF was associated with an increased risk for rejection.

A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis.

OBJECTIVES: Medical therapy of refractory ulcerative colitis (UC) is associated with long-term side effects of cyclosporine and steroids. Because cyclosporine acts by inhibiting interleukin-2 (IL-2) production, we studied the efficacy and safety of humanized anti-IL2 receptor (CD25) antibodies daclizumab for refractory UC in an open label pilot study. METHODS: Ten patients with chronically active UC received daclizumab, 1 mg/kg i.v. twice with a 4-wk interval. Clinical, endoscopic, and histological evaluation was scored at regular intervals. CD25 immunohistochemistry was followed in mucosal biopsies. The primary study endpoint was clinical improvement at wk 8. RESULTS: Nine of 10 patients completed the study. The median clinical activity score decreased from a median of 8 (95% CI = 7.2-9.2) at baseline to 3.5 (95% CI = 1.4-4.9) at wk 8 (p < 0.005). Endoscopic scores were significantly decreased at wk 8 (wk 0: 8, 95% CI = 6.3-8.5; wk 8: 5.0, 95% CI = 2.6-6.3; p < 0.01). Mucosal biopsies showed a significant decrease in CD25+ cells, and there was a trend toward lower histology scores at wk 8. Quality of life as assessed by the Inflammatory Bowel Disease Questionnaire increased after therapy (baseline: 131, 95% CI = 119-178; wk 8: 169; 95% CI = 124-216, p < 0.05). Nausea was most frequently reported as an adverse event, but always in patients that were concomitantly started on azathioprine. CONCLUSIONS: The anti-IL-2R antibody daclizumab was safe and well tolerated in acute UC. Patients experienced clinical benefit along with signs of endoscopic improvement, but further controlled trials are needed to determine the therapeutic benefit of this compound.