Context.— Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery. Objective.— To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics. Data Sources.— The review and analysis of the latest literature describing pancreatic cystic lesions. Conclusions.— Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing.

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Purpose: This phase 1b/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0)received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response (pCR [ypT0N0]). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met (7/31 [22.6%] achieved pCR). Patients with high (ie, combined positive score [CPS] {greater than or equal to}10) baseline expression of PD-L1 in the TME had a significantly higher pCR rate than those with low expression (50.0% [4/8] vs 13.6% [3/22]; P=.046). Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS <10, unprespecified analysis explored whether extracellular vesicles (EVs) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR. Conclusions:Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.

Since its inception in 1988 the Cochlear Implant Programme in Manchester has successfully implanted 69 adults and 23 children. Of these 92 procedures, three patients have undergone revision surgery with the insertion of either a new implant or re-positioning of the existing device. We examine the circumstances that lead to the need for reimplantation in these patients, discuss the technical aspects of revision surgery together with the functional results of such procedures.

FNA specimens are a more optimal source of DNA, and represent an important resource in the preresection and postresection molecular analysis of pancreatic ductal adenocarcinoma. Cancer Cytopathol 2017;125:838-47. © 2017 American Cancer Society.

Context.— Fatty liver disease is now one of the most commonly encountered entities in the practice of liver pathology. Distinguishing simple steatosis from steatohepatitis is critical because the latter requires follow-up because of long-term risks that include cirrhosis and hepatocellular carcinoma. An organized approach for evaluating liver biopsies with steatosis is recommended to capture all of the relevant features: (1) degree of steatosis, (2) presence or absence of ballooning degeneration, (3) lobular inflammation, and (4) fibrosis. Herein, we provide a stepwise approach that readers can use to evaluate liver biopsies with steatosis, including examples, pitfalls, differential diagnostic considerations, and suggested diagnostic phrasing. Objective.— To provide a stepwise approach for the evaluation of liver biopsies showing significant steatosis (involving ≥5% of liver parenchyma). Data Sources.— Biopsies demonstrating fatty liver disease encountered in our daily practice were examined as well as recent literature. Conclusions.— Effective evaluation of liver biopsies with steatosis requires careful histologic examination and correlation with clinical history, particularly regarding medications, nutrition status, and alcohol use. Examples of uniform reporting, including appropriate use of the nonalcoholic steatohepatitis Clinical Research Network Activity Score, are provided.

These findings suggest a pathophysiologic link between CD30 activity and Tregs and may indicate differential expression of CD30 in B-cell lymphomas arising in the setting of immune dysregulation.

BACKGROUND Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non–small cell lung cancer (NSCLC). The current diagnostic test for ALK rearrangement is breakapart fluorescence in situ hybridization (FISH), but FISH has low throughput and is not always reflective of protein concentrations. The emergence of multiple clinically relevant biomarkers in NSCLC necessitates efficient testing of scarce tissue samples. We developed an anaplastic lymphoma kinase (ALK) protein assay that uses multiplexed selected reaction monitoring (SRM) to quantify absolute amounts of ALK in formalin-fixed paraffin-embedded (FFPE) tumor tissue. METHODS After validation in formalin-fixed cell lines, the SRM assay was used to quantify concentrations of ALK in 18 FFPE NSCLC samples that had been tested for ALK by FISH and immunohistochemistry. Results were correlated with patient response to crizotinib. RESULTS We detected ALK in 11 of 14 NSCLC samples with known ALK rearrangements by FISH. Absolute ALK concentrations correlated with clinical response in 5 of 8 patients treated with crizotinib. The SRM assay did not detect ALK in 3 FISH-positive patients who had not responded to crizotinib. In 1 of these cases, DNA sequencing revealed a point mutation that predicts a nonfunctional ALK fusion protein. The SRM assay did not detect ALK in any tumor tissue with a negative ALK status by FISH or immunohistochemistry. CONCLUSIONS ALK concentrations measured by SRM correlate with crizotinib response in NSCLC patients. The ALK SRM proteomic assay, which may be multiplexed with other clinically relevant proteins, allows for rapid identification of patients potentially eligible for targeted therapies.