Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Formalin-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer.

Before initiating treatment of advanced non-small-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15-center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from non-small-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.

Topographic mapping of a specimen after endoscopic submucosal dissection.

Background and study aims Mapping of pathologic specimens after endoscopic submucosal dissection (ESD) is common practice in Asian countries, especially in Japan. However, there is a lack of awareness for this technique in Europe. In this report, we demonstrate the feasibility and benefits of topographic mapping in a Western setting.

Engraftment and reversal of diabetes after intramuscular transplantation of neonatal porcine islet-like clusters.

BACKGROUND: Intraportal infusion is currently the method of choice for clinical islet cell transplantation but suffers from poor efficacy. As the liver may not represent an optimal transplantation site for Langerhans islets, we examined the potential of neonatal porcine islet-like clusters (NPICCs) to engraft in skeletal muscle as an alternative transplantation site. METHODS: Neonatal porcine islet-like clusters were isolated from 2- to 5-day-old piglets and either transplanted under the kidney capsule (s.k.) or injected into the lower hindlimb muscle (i.m.) of streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice. Survival, vascularization, maturation, and functional activity were analyzed by intraperitoneal glucose tolerance testing and immunohistochemical analyses. RESULTS: Intramuscular transplantation of NPICCs resulted in development of normoglycemia and restored glucose homeostasis. Time to reversal of diabetes and glucose tolerance (AUC glucose and AUC insulin) did not significantly differ as compared to s.k. transplantation. Intramuscular grafts exhibited rapid neovascularization and graft composition with cytokeratin-positive ductal cells and beta cells at post-transplant weeks 2 and 8 and after establishment of normoglycemia was comparable in both groups. CONCLUSIONS: Intramuscular injection represents a minimally invasive but efficient alternative for transplantation of NPICCs and, thus, offers an attractive alternative site for xenotransplantation approaches. These findings may have important implications for improving the outcome and the monitoring of pig islet xenotransplantation.

Refractory idiopathic non-insulinoma pancreatogenous hypoglycemia in an adult: case report and review of the literature.

CONTEXT: Non-insulinoma pancreatogenous hypoglycemia is a rare cause of spontaneous hypoglycemia in adults. The ideal diagnostic and therapeutic approach is still controversial, not least because most reported cases lack long-term follow-up. CASE REPORT: We describe the case of a 58-year-old woman, who was diagnosed with idiopathic non-insulinoma pancreatogenous hypoglycemia in 2001. After resection of 75% of the distal pancreas, she initially experienced no additional hypoglycemic episodes and did not suffer from diabetes mellitus. However, after one month, recurrent hypoglycemia occurred. After resection of the larger part of the remaining pancreatic tissue, the patient suffered from hypoglycemic as well as hyperglycemic episodes. Octreotide and diazoxide were not successful in preventing the hypoglycemic attacks, whereas continuous insulin therapy with an insulin pump helped to stabilize the blood glucose level temporarily. Finally, all remaining pancreatic tissue had to be removed. CONCLUSION: This long-term follow-up of non-insulinoma pancreatogenous hypoglycemia treatment in an adult patient indicates that lateral pancreatectomy may not be sufficient for permanent blood glucose control and emphasizes the need of follow-up data after subtotal pancreatectomy.