Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.

Posttransplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent uncommon complications of transplantation and can lead to significant morbidity and mortality. PTLD is most prevalent during the first year following transplantation and occurs most frequently in multiorgan transplant recipients, followed by bowel, heart-lung, and lung recipients. It may involve any of the organ systems, with disease manifestation and the anatomic pattern of organ involvement being highly dependent on the type of transplantation. The current classification system includes four subtypes that have different prognoses requiring different treatment strategies. Tissue sampling is necessary for diagnosis and further subcategorization. The majority of cases are characterized by B-cell proliferation and are related to infection from Epstein-Barr virus. Knowledge of the distribution and radiologic features of PTLD allows the radiologist to play a pivotal role in making an early diagnosis and in guiding biopsy.

Understanding the characteristic appearances of primary gallbladder carcinoma at multiple imaging modalities can facilitate diagnosis and enable more accurate staging for triage to extended resection or an alternate therapy.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The macroscopic growth pattern of HCC is subdivided into three categories: nodular, massive, and infiltrative. Infiltrative HCC accounts for 7%-20% of HCC cases and is confirmed at pathologic analysis on the basis of the spread of minute tumor nodules throughout large regions of the liver. Infiltrative HCC may represent a diagnostic challenge because it is often difficult to distinguish from background changes in cirrhosis at imaging. Infiltrative HCC usually spreads over multiple hepatic segments, occupying an entire hepatic lobe or the entire liver, and it is frequently associated with portal vein tumor thrombosis. The tumor is usually ill defined at ultrasonography and shows minimal and inconsistent arterial enhancement and heterogeneous washout at contrast material-enhanced computed tomography and magnetic resonance (MR) imaging. The tumor may be more visible among the surrounding liver parenchyma at diffusion-, T1-, and T2-weighted MR imaging. Several liver diseases can mimic the infiltrative appearance of this malignancy, including focal confluent fibrosis, hepatic fat deposition, hepatic microabscesses, intrahepatic cholangiocarcinoma, and diffuse metastatic disease (pseudocirrhosis). The prognosis for patients with infiltrative HCC is poor because the tumor is often markedly advanced and associated with vascular invasion at presentation. Survival after surgical resection is decreased; thus, infiltrative HCC is a contraindication for resection and transplantation. Knowledge of the key tumor characteristics and imaging findings will help radiologists formulate a correct and timely diagnosis to improve patient management.

The number and morphology of the lesions and determination of whether there is a solid component are key imaging features that are helpful for approaching the diagnosis of cystic hepatic lesions. Familiarity with these features and knowledge of the clinical associations will help the radiologist to establish a definitive diagnosis or provide a reasonable differential diagnosis.

Purpose:The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC), and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients 'at-risk' for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm.Methods: This retrospective study combined a 10-year experience of pathologically-proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator. Results:The final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes (5 [2.8%] and 3 [1.7%] for reader 1 and reader 2, respectively) in overall lesion classification.

The widespread use of high-spatial-resolution cross-sectional imaging has led to an increase in detection of incidental pancreatic cystic lesions. These lesions are a diverse group, ranging from indolent and premalignant lesions to invasive cancers. The diagnosis of several of these lesions can be suggested on the basis of their imaging appearance, while many other lesions require follow-up imaging and/or aspiration. The smaller cystic lesions, often branch-duct intraductal papillary mucinous neoplasms, have overlapping imaging characteristics that make diagnostic assessment of the natural history and malignancy risk confusing. Expert panels have developed societal guidelines, based on a consensus, for surveillance of these lesions. However, these guidelines are often inconsistent and are constantly evolving as additional scientific data are accumulated. Identification of features associated with increased risk of malignancy is important for proper management. The concept of field defect, whereby pancreatic adenocarcinoma develops at a site different from the site of the pancreatic cyst, adds to the complexity of screening guidelines. As a result of the differences in guidelines, key stakeholders (eg, radiologists, gastroenterologists, and surgeons) must review and come to a consensus regarding which guideline, or combination of guidelines, to follow at their individual institutions. Standardized reporting and macros are helpful for ensuring the uniformity of interpretations. Radiologists play a critical role in the detection and characterization of pancreatic cystic lesions, in the follow-up recommendations for these lesions, and in the detection of associated cancer.

Purpose Objective responses are reported in 34% to 37% of patients with programmed death-1 (PD-1)–naïve advanced melanoma treated with PD-1 inhibitors. Pre-existing CD8+ T-cell infiltrate and interferon (IFN) gene signature correlate with response to PD-1 blockade. Here, we report a phase Ib/II study of pembrolizumab/pegylated (PEG)-IFN combination in PD-1–naïve advanced melanoma. Patients and Methods PEG-IFN (1, 2, and 3 μg/kg per week) was dose escalated using a modified toxicity probability interval design in three cohorts of four patients each, whereas pembrolizumab was dosed at 2 mg/kg every 3 weeks in the phase Ib portion. Thirty-one patients were enrolled in the phase II portion. Primary objectives were safety and incidence of dose-limiting toxicities. Secondary objectives included objective response rate, progression-free survival (PFS), and overall survival. Results Forty-three patients with stage IV melanoma were enrolled in the phase Ib and II portions of the study and included in the analysis. At the data cutoff date (December 31, 2017), median follow-up duration was 25 months (range, 1 to 38 months). All 43 patients experienced at least one adverse event; grade 3/4 treatment-related adverse events occurred in 21 of 43 patients (48.8%). Objective responses were seen at all three dose levels among 43 evaluable patients. The objective response rate was 60.5%, with 46.5% of patients exhibiting ongoing response. Median PFS was 11.0 months in all patients and unreached in responders, whereas median overall survival remained unreached in all patients. The 2-year PFS rate was 46%. Conclusion Pembrolizumab/PEG-IFN demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in PD-1–naïve metastatic melanoma. These results support the rationale to further investigate this pembrolizumab/PEG-IFN combination in this disease.