ABSTRACT
OBJECTIVE: Rearranged ROS1, present in 1%-2% of non-small cell lung cancer (NSCLC) patients, usually young, never or light smokers, is assessed by fluorescence in situ hybridization (FISH) to determine eligibility for tyrosine kinase inhibitors (TKI). Immunohistochemistry (IHC) for the protein product of ROS1 rearrangement, a cost-effective alternative, is validated on cytology and small biopsy samples. METHODS: From 1 March to 31 December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion next generation sequencing (NGS) panel. RESULTS: In a prospective population of 95 cases, 91 were negative and two were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another two cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation, whilst that of FISH was 9 to 42 days at a cost of £51 and £159 respectively. CONCLUSION: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good negative predictive value, faster turnaround time and is cost effective, with proven technical and clinical validation.
Subject(s)
Biopsy/methods , Cytodiagnosis/methods , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/metabolism , Female , Hospitals, Teaching/methods , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing because of its antiangiogenic, anti-inflammatory, and antioxidant properties. We previously showed the role of EGCG in scarring in ex vivo human scar models. Here, we evaluate direct application of topical EGCG compared with zonal priming, a unique concept in the immediate treatment of the zone of injury at the time of wounding before scar formation. TRIAL DESIGN: Double-blind randomized controlled trial. METHODS: We assessed EGCG application compared with placebo over 1-6 weeks in scars created in 62 human volunteers using quantitative noninvasive devices, immunohistochemical analysis, mRNA sequencing, and quantitative real-time reverse transcriptase-PCR of tissue biopsy samples. RESULTS: EGCG reduced mast cells at weeks 1-3, as evidenced by gene and protein analyses (P ≤ 0.01). M2 macrophages were increased with EGCG compared with placebo. EGCG application by zonal priming significantly down-regulated VEGFA and CD31 at week 1 and at 1-2 weeks after direct application (P ≤ 0.01). Direct EGCG application also reduced scar thickness at weeks 1-3 (P = 0.001) and increased scar elasticity at week 4 (P = 0.01). Increased hydration was evident both noninvasively and by increased hyaluronic acid levels (P < 0.01) at week 3. CONCLUSIONS: We show the beneficial role of both zonal priming and direct EGCG application in scar therapy with positive effects on scar thickness, erythema, hydration, and elasticity. Trial register: International standard randomized controlled trial, registration number ISRCTN 18643079; July 16, 2018.
Subject(s)
Catechin/analogs & derivatives , Cicatrix/prevention & control , Skin/injuries , Wounds and Injuries/complications , Administration, Cutaneous , Adult , Catechin/administration & dosage , Cicatrix/etiology , Double-Blind Method , Female , Humans , Male , Skin/drug effects , Treatment Outcome , Young AdultABSTRACT
Lymphoepithelial cysts (LECs) of the pancreas are rare true pancreatic cysts. Their cause is not known. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. In this study, we report the largest LEC of the pancreas to have been resected laparoscopically. A 43-year-old man presented with upper abdominal pain, a 7.5 cm mutlioculated cystic mass in the pancreatic body and tail on imaging, and a raised serum cancer antigen-19-9. Laparoscopic distal pancreatectomy and splenectomy was performed. Histologic examination revealed a LEC. This study discusses the diagnostic difficulties and management decisions which face surgeons treating pancreatic cysts.
