Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation.

Immunotherapy with checkpoint inhibitors is well established as an effective treatment for non-small cell lung cancer and melanoma. The list of approved indications for treatment with PD-1/PD-L1 checkpoint inhibitors is growing rapidly as clinical trials continue to show their efficacy in patients with a wide range of solid tumours. Clinical trials have used a variety of PD-L1 immunohistochemical assays to evaluate PD-L1 expression on tumour cells, immune cells or both as a potential biomarker to predict response to immunotherapy. Requests to pathologists for PD-L1 testing to guide choice of therapy are rapidly becoming commonplace. Thus, pathologists need to be aware of the different PD-L1 assays, methods of evaluation in different tumour types and the impact of the results on therapeutic decisions. This review discusses the key practical issues relating to the implementation of PD-L1 testing for solid tumours in a pathology laboratory, including evidence for PD-L1 testing, different assay types, the potential interchangeability of PD-L1 antibody clones and staining platforms, scoring criteria for PD-L1, validation, quality assurance, and pitfalls in PD-L1 assessment. This review also explores PD-L1 IHC in solid tumours including non-small cell lung carcinoma, head and neck carcinoma, triple negative breast carcinoma, melanoma, renal cell carcinoma, urothelial carcinoma, gastric and gastroesophageal carcinoma, colorectal carcinoma, hepatocellular carcinoma, and endometrial carcinoma. The review aims to provide pathologists with a practical guide to the implementation and interpretation of PD-L1 testing by immunohistochemistry.

Risk of bacterial colonization of pancreatic stents used in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Pancreatic stents (PSs) are commonly inserted at the time of endoscopic retrograde cholangiopancreatography to reduce the risk of pancreatitis. If left in situ for more than 2 weeks, they have been associated with pancreatic duct injury. The mechanism of this injury is not clear, but it may be related to bacterial colonization. AIM: : To determine the incidence of PS colonization by microorganisms and the relationship between such colonization and the type, length, diameter, and duration of PSs in situ. METHODS: A series of endoscopic retrograde cholangiopancreatographies performed by a single operator in a tertiary referral centre during which a PS was placed was analysed. In each case, after removing the PS, the segment of the PS, which had been intraluminal, was sent for microbiological analysis. Microscopy and culture results were compared with stent length (cm), time in situ (d), demographic information, and clinical course. RESULTS: Of the 47 PSs sent for culture, 28 grew clinically significant bacteria. The majority of organisms cultured were of the Klebsiella, Escherichia, Enterobacter, and Enterococcus genera. Time in situ was found to correlate strongly with the growth of clinically significant organisms using a logarithmic regression analysis tool (coefficient=0.36, change of variance=6.43, P=0.01). In addition, 1 patient developed Enterobacter septicaemia almost certainly related to stent colonization, which necessitated urgent removal of the stent 10 days after insertion. CONCLUSION: Colonization of PSs by pathogenic organisms is common and related to duration in situ of the PS. Enteric organisms are frequently implicated. Although significant clinical sequelae are infrequent, we suggest that PSs should not be left in situ for >7 to 10 days due to the significant risk of bacterial colonization.