High Pretreatment DHEA Is Associated with Inferior Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer.

Background: Sex difference in the immune response may influence patients' response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Method: Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 ß-estradiol, 5-androstenediol, 3ß-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Result: Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7-43); p < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89-23.35); p < 0.0001]. Conclusions: High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.

Early Adverse Event Derived Biomarkers in Predicting Clinical Outcomes in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy.

RATIONALE: Adverse events (AEs) have been shown to have clinical associations, in addition to patient safety assessments of drugs of interest. However, due to their complex content and associated data structure, AE evaluation has been restricted to descriptive statistics and small AE subset for efficacy analysis, limiting the opportunity for global discovery. This study takes a unique approach to utilize AE-associated parameters to derive a set of innovative AE metrics. Comprehensive analysis of the AE-derived biomarkers enhances the chance of discovering new predictive AE biomarkers of clinical outcomes. METHODS: We utilized a set of AE-associated parameters (grade, treatment relatedness, occurrence, frequency, and duration) to derive 24 AE biomarkers. We further innovatively defined early AE biomarkers by landmark analysis at an early time point to assess the predictive value. Statistical methods included the Cox proportional hazards model for progression-free survival (PFS) and overall survival (OS), two-sample t-test for mean difference of AE frequency and duration between disease control (DC: complete response (CR) + partial response (PR) + stable disease (SD)) versus progressive disease (PD), and Pearson correlation analysis for relationship of AE frequency and duration versus treatment duration. Two study cohorts (Cohort A: vorinostat + pembrolizumab, and B: Taminadenant) from two immunotherapy trials in late-stage non-small cell lung cancer were used to test the potential predictiveness of AE-derived biomarkers. Data from over 800 AEs were collected per standard operating procedure in a clinical trial using the Common Terminology Criteria for Adverse Events v5 (CTCAE). Clinical outcomes for statistical analysis included PFS, OS, and DC. RESULTS: An early AE was defined as event occurrence at or prior to day 30 from initial treatment date. The early AEs were then used to calculate the 24 early AE biomarkers to assess overall AE, each toxicity category, and each individual AE. These early AE-derived biomarkers were evaluated for global discovery of clinical association. Both cohorts showed that early AE biomarkers were associated with clinical outcomes. Patients previously experienced with low-grade AEs (including treatment related AEs (TrAE)) had improved PFS, OS, and were associated with DC. The significant early AEs included low-grade TrAE in overall AE, endocrine disorders, hypothyroidism (pembrolizumab's immune-related adverse event (irAE)), and platelet count decreased (vorinostat related TrAE) for Cohort A and low-grade AE in overall AE, gastrointestinal disorders, and nausea for Cohort B. In contrast, patients with early development of high-grade AEs tended to have poorer PFS, OS, and correlated with PD. The associated early AEs included high-grade TrAE in overall AE, gastrointestinal disorders with two members, diarrhea and vomiting, for Cohort A and high-grade AE in overall AE, three toxicity categories, and five related individual AEs for Cohort B. One low-grade TrAE, alanine aminotransferase increased (vorinostat + pembrolizumab related), was an irAE and correlated with worse OS in Cohort A. CONCLUSIONS: The study demonstrated the potential clinical utility of early AE-derived biomarkers in predicting positive and negative clinical outcomes. It could be TrAEs or combination of TrAEs and nonTrAEs from overall AEs, toxicity category AEs, to individual AEs with low-grade event leaning to encouraging effect and high-grade event to undesirable impact. Moreover, the methodology of the AE-derived biomarkers could change current AE analysis practice from a descriptive summary into modern informative statistics. It modernizes AE data analysis by helping clinicians discover novel AE biomarkers to predict clinical outcomes and facilitate the generation of vast clinically meaningful research hypotheses in a new AE content to fulfill the demands of precision medicine.

Pancreatic colloid adenocarcinoma arising from intraductal papillary mucinous neoplasm: Radiologic-pathologic correlation with cinematic rendering.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas have the potential for malignant progression into adenocarcinoma. Colloid or mucinous non-cystic carcinoma of the pancreas is an uncommon variant neoplasm that can arise within an intestinal type IPMN and have a relatively improved prognosis but may mimic the more lethal tubular or ductal adenocarcinoma. Colloid carcinoma is an infiltrating ductal epithelial neoplasm containing primarily extracellular stromal mucin pools and scant amount of centrally floating neoplastic cells. While several reports have evaluated the unique pathologic and immunohistochemical profile of colloid carcinomas, there has been limited radiologic-pathologic correlation in the literature. We report a case of an 83-year-old female who presented for evaluation of slowly progressive abdominal pain and was found to have colloid carcinoma arising from an IPMN. This is one of the first reports to correlate the multimodality radiology including cinematic rendering (CR) and histopathology features associated with this tumor. An enhanced understanding of the correlation between imaging appearance and specific histopathologic findings may aid in the early recognition and treatment of this rare neoplasm. Emphasis is placed on CR as this may help guide surgical management.

Dose-Limiting Pulmonary Toxicity in a Phase 1/2 Study of Radiation and Chemotherapy with Ipilimumab Followed by Nivolumab for Patients With Stage 3 Unresectable Non-Small Cell Lung Cancer.

PURPOSE: We hypothesized that concurrent ipilimumab with chemoradiationtherapy (chemoRT) followed by maintenance nivolumab would be safe for patients with unresectable stage III non-small cell lung cancer (NSCLC). We aimed to assess the safety (phase 1) and the 12-month progression-free survival (PFS) (phase 2) in a multi-institution prospective trial. METHODS AND MATERIALS: Eligible patients had unresectable stage III NSCLC. The treatment included platinum doublet chemotherapy with concurrent thoracic radiation therapy to 60 Gy in 30 fractions and ipilimumab (1 mg/kg) delivered during weeks 1 and 4. After chemoRT, maintenance nivolumab (480 mg) was given every 4 weeks for up to 12 cycles. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 5.0. Survival analyses were performed with Kaplan Meier (KM) methods and log-rank tests. RESULTS: The trial was discontinued early after enrolling 19 patients without proceeding to the phase 2 component because of unacceptable toxicity. Sixteen patients (84%) had grade ≥3 (G3+) possible treatment-related toxicity, most commonly pulmonary AEs (n = 8, 42%). Fourteen patients (74%) discontinued study therapy early because of AEs (n = 12, 63%) or patient choice (n = 2, 11%). Eleven patients (58%) experienced G2+ pulmonary toxicity with median time to onset 4.1 months (95% CI 2.6-not reached [NR]), and 12-month freedom from G2+ pulmonary toxicity 37% (95% CI, 16-59). Five patients had G5 AEs, including 3 with G5 pulmonary AEs (1 respiratory failure with pneumonitis and pulmonary embolism, 1 pneumonia/chronic obstructive pulmonary disease exacerbation, 1 pulmonary fibrosis). Despite toxicities, the median PFS was 19.2 months (95% CI 6.1-NR) and the median overall survival was NR (95% CI 6.1-NR) with median follow-up of 30.1 months by the reverse KM method. CONCLUSIONS: Concurrent ipilimumab with chemoRT for unresectable stage III NSCLC is associated with pulmonary toxicity that may limit opportunities for improved outcomes. Future studies aiming to incorporate ipilimumab or other anti-CTLA4 therapies into management of unresectable stage III NSCLC should consider careful measures to minimize toxicity risk.

Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial.

BACKGROUND: Merkel cell carcinoma is among the most aggressive and lethal of primary skin cancers, with a high rate of distant metastasis. Anti-programmed death receptor 1 (anti-PD-1) and programmed death ligand 1 (PD-L1) monotherapy is currently standard of care for unresectable, recurrent, or metastatic Merkel cell carcinoma. We assessed treatment with combined nivolumab plus ipilimumab, with or without stereotactic body radiotherapy (SBRT) in patients with advanced Merkel cell carcinoma as a first-line therapy or following previous treatment with anti-PD-1 and PD-L1 monotherapy. METHODS: In this randomised, open label, phase 2 trial, we randomly assigned adults from two cancer sites in the USA (one in Florida and one in Ohio) to group A (combined nivolumab and ipilimumab) or group B (combined nivolumab and ipilimumab plus SBRT) in a 1:1 ratio. Eligible patients were aged at least 18 years with histologically proven advanced stage (unresectable, recurrent, or stage IV) Merkel cell carcinoma, a minimum of two tumour lesions measureable by CT, MRI or clinical exam, and tumour tissue available for exploratory biomarker analysis. Patients were stratified by previous immune-checkpoint inhibitor (ICI) status to receive nivolumab 240 mg intravenously every 2 weeks plus ipilimumab 1 mg/kg intravenously every 6 weeks (group A) or the same schedule of combined nivolumab and ipilimumab with the addition of SBRT to at least one tumour site (24 Gy in three fractions at week 2; group B). Patients had to have at least two measurable sites of disease so one non-irradiated site could be followed for response. The primary endpoint was objective response rate (ORR) in all randomly assigned patients who received at least one dose of combined nivolumab and ipilimumab. ORR was defined as the proportion of patients with a complete response or partial response per immune-related Response Evaluation Criteria in Solid Tumours. Response was assessed every 12 weeks. Safety was assessed in all patients. This trial is registered with ClinicalTrials.gov, NCT03071406. FINDINGS: 50 patients (25 in both group A and group B) were enrolled between March 14, 2017, and Dec 21, 2021, including 24 ICI-naive patients (13 [52%] of 25 group A patients and 11 [44%] of 25 group B patients]) and 26 patients with previous ICI (12 [48%] of 25 group A patients and 14 [56%] of 25 group B patients]). One patient in group B did not receive SBRT due to concerns about excess toxicity. Median follow-up was 14·6 months (IQR 9·1-26·5). Two patients in group B were excluded from the analysis of the primary endpoint because the target lesions were irradiated and so the patients were deemed non-evaluable. Of the ICI-naive patients, 22 (100%) of 22 (95% CI 82-100) had an objective response, including nine (41% [95% CI 21-63]) with complete response. Of the patients who had previously had ICI exposure, eight (31%) of 26 patients (95% CI 15-52) had an objective response and four (15% [5-36]) had a complete response. No significant differences in ORR were observed between groups A (18 [72%] of 25 patients) and B (12 [52%] of 23 patients; p=0·26). Grade 3 or 4 treatment-related adverse events were observed in 10 (40%) of 25 patients in group A and 8 (32%) of 25 patients in group B. INTERPRETATION: First-line combined nivolumab and ipilimumab in patients with advanced Merkel cell carcinoma showed a high ORR with durable responses and an expected safety profile. Combined nivolumab and ipilimumab also showed clinical benefit in patients with previous anti-PD-1 and PD-L1 treatment. Addition of SBRT did not improve efficacy of combined nivolumab and ipilimumab. The combination of nivolumab and ipilimumab represents a new first-line and salvage therapeutic option for advanced Merkel cell carcinoma. FUNDING: Bristol Myers Squibb Rare Population Malignancy Program.

Utilization of target lesion heterogeneity for treatment efficacy assessment in late stage lung cancer.

RATIONALE: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve RECIST response classification. METHOD: An approach for Lesion Heterogeneity Classification (LeHeC) was developed using a contemporary statistical approach to assess target lesion variation, characterize patient treatment response, and translate informative evidence to improving treatment strategy. A mixed effect linear model was used to determine lesion heterogeneity. Further analysis was conducted to classify various types of lesion variation and incorporate with RECIST to enhance response classification. A study cohort of 110 target lesions from 36 lung cancer patients was used for evaluation. RESULTS: Due to small sample size issue, the result was exploratory in nature. By analyzing RECIST target lesion data, the LeHeC approach detected a high prevalence (n = 21; 58%) of lesion heterogeneity. Subgroup classification revealed several informative distinct subsets in a descending order of lesion heterogeneity: mix of progression and regression (n = 7), mix of progression and stability (n = 9), mix of regression and stability (n = 5), and non-heterogeneity (n = 15). Evaluation for association of lesion heterogeneity and RECIST best response classification showed lesion heterogeneity commonly occurred in each response group (stable disease: 16/27; 59%; partial response: 3/5; 60%; progression disease: 2/4; 50%). Survival analysis showed a differential trend of overall survival between heterogeneity and non-heterogeneity in RECIST response groups. CONCLUSION: This is the first study to evaluate lesion heterogeneity, an underappreciated metric, for RECIST application in oncology clinical trials. Results indicated lesion heterogeneity is not an uncommon event. The LeHeC approach could enhance RECIST response classification by utilizing granular lesion level discovery of heterogeneity.

Diffuse intrasinusoidal hepatic metastasis from breast cancer: Multimodality imaging with pathology correlation.

Metastatic disease to the liver is a known and common site of breast cancer spread, classically presenting as either hypovascular or hypervascular masses. Rarely, hepatic metastatic disease may have an atypical diffuse and intrasinusoidal pattern of involvement, which may be radiographically occult or extremely challenging to diagnose even with multiphase contrast enhanced techniques. We report a case of a 28-year-old female with stage III invasive ductal carcinoma of the breast, who recently discontinued treatment due to pregnancy, presenting with progressive signs and symptoms of rapidly decompensating liver failure due to sinusoidal obstruction. Multimodality imaging was performed without evidence for focal hepatic metastatic disease; however, intrahepatic vein (IVC) compression was noted. Hepatic sinusoidal tumor infiltration was confirmed by liver biopsy. After palliative chemotherapy the disease became less infiltrative and more conspicuous on imaging, revealing itself as hepatic metastases, with decreased compression of the intrahepatic IVC and resolution of signs and symptoms of sinusoidal obstruction syndrome.

Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer.

PURPOSE: Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer. METHODS AND MATERIALS: Eligibility required stable disease or better after platinum doublet chemotherapy. Study therapy included consolidative TRT to 30 Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks for 4 doses followed by NIVO monotherapy (480 mg) every 4 weeks until progression or up to 1 year. RESULTS: The study enrolled 21 patients, with 6-month progression-free survival (PFS) of 24% (90% confidence interval [CI], 11%-40%) and a median PFS of 4.5 months (95% CI, 2.7%-4.6%). The 12-month overall survival (OS) was 48% (95% CI, 29%-64%) with a median OS of 11.7 months (95% CI, 4.7%-16.0%). Fifty-two percent of patients had ≥1 possibly related grade 3 to 4 immune-related adverse event. Grade 3 pulmonary and gastrointestinal immune-related adverse events were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P = .01) and OS (P = .02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P = .02) and OS (P = .02). CONCLUSIONS: Consolidative IPI and NIVO after platinum-based chemotherapy and TRT demonstrated a toxicity profile consistent with the known adverse events attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in small cell lung cancer.

Multi-Omics and Informatics Analysis of FFPE Tissues Derived from Melanoma Patients with Long/Short Responses to Anti-PD1 Therapy Reveals Pathways of Response.

Anti-PD-1 based immune therapies are thought to be dependent on antigen processing and presentation mechanisms. To characterize the immune-dependent mechanisms that predispose stage III/IV melanoma patients to respond to anti-PD-1 therapies, we performed a multi-omics study consisting of expression proteomics and targeted immune-oncology-based mRNA sequencing. Formalin-fixed paraffin-embedded tissue samples were obtained from stage III/IV patients with melanoma prior to anti-PD-1 therapy. The patients were first stratified into poor and good responders based on whether their tumors had or had not progressed while on anti-PD-1 therapy for 1 year. We identified 263 protein/gene candidates that displayed differential expression, of which 223 were identified via proteomics and 40 via targeted-mRNA analyses. The downstream analyses of expression profiles using MetaCore software demonstrated an enrichment of immune system pathways involved in antigen processing/presentation and cytokine production/signaling. Pathway analyses showed interferon (IFN)-γ-mediated signaling via NF-κB and JAK/STAT pathways to affect immune processes in a cell-specific manner and to interact with the inducible nitric oxide synthase. We review these findings within the context of available literature on the efficacy of anti-PD-1 therapy. The comparison of good and poor responders, using efficacy of PD-1-based therapy at 1 year, elucidated the role of antigen presentation in mediating response or resistance to anti-PD-1 blockade.

Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal adenocarcinoma. Currently, the International Consensus Guidelines (ICG) for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography (CT) imaging. Despite using the ICG, it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection. A supplementary quantitative radiological tool, radiomics, may improve diagnostic accuracy of radiological evaluation of IPMNs. We hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN histology. AIM: To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus Guidelines. METHODS: Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective cohort. Whole lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software (Healthmyne, Madison, WI). Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast phase. Univariate analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic regression. Conventional quantitative and qualitative CT measurements were also compared between groups, via χ 2 (categorical) and Mann Whitney U (continuous) variables. RESULTS: Twenty-nine subjects (15 males, age 71 ± 9 years) with high grade or invasive tumor histology comprised the "malignant" cohort, while 22 subjects (11 males, age 70 ± 7 years) with low grade tumor histology were included in the "benign" cohort. Radiomic analysis showed 18/39 precontrast, 19/39 arterial phase, and 21/39 venous phase features differentiated malignant from benign IPMNs (P < 0.05). Multivariate analysis including only ICG criteria yielded two significant variables: thickened and enhancing cyst wall and enhancing mural nodule < 5 mm with an AUC (95%CI) of 0.817 (0.709-0.926). Multivariable post contrast radiomics achieved an AUC (95%CI) of 0.87 (0.767-0.974) for a model including arterial phase radiomics features and 0.834 (0.716-0.953) for a model including venous phase radiomics features. Combined multivariable model including conventional variables and arterial phase radiomics features achieved an AUC (95%CI) of 0.93 (0.85-1.0) with a 5-fold cross validation AUC of 0.90. CONCLUSION: Multi-phase CT radiomics evaluation could play a role in improving predictive capability in diagnosing malignancy in IPMNs. Future larger studies may help determine the clinical significance of our findings.

A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection.

Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC.

Chronic Anthracycline-related Myocarditis Presenting as Diffuse Myocardial Calcification.

In the setting of cardio-oncology, evaluation for myocarditis is a growing indication for cardiovascular magnetic resonance (CMR). Treatment-related side effects of cancer therapies comprise the majority of myocarditis cases in cardio-oncology, and these are often secondary to anthracyclines and even the newer class of immune checkpoint inhibitors. Cardiotoxicity from cancer therapy represents an increasingly recognized etiology of myocarditis and when detected, warrants prompt management changes. The conventional CMR evaluation for myocarditis includes modules for the left ventricular structure and function, early gadolinium enhancement, and late gadolinium enhancement. Newer CMR sequences including native T1 mapping and extracellular volume fraction offer improvement in diagnostic accuracy from conventional CMR methods. We present a case of subacute/ chronic myocarditis related to anthracycline therapy 4 months prior that was diagnosed only after incidental diffuse myocardial calcifications on pre-treatment computed tomography raised suspicion.

A Pictorial Essay of Immunotherapy: Complications that Internists Will See, Whether They Like it or Not.

Immunotherapy agents for treatment of cancer have been investigated for decades, but effective agents have only recently been identified and are increasingly being used in multiple cancer types. There is growing recognition of adverse side effects in multiple organ systems mediated by dysregulation of the immune system, which can be exacerbated by comorbidities often found in cancer patients such as chronic lung disease, diabetes, and hypertension. As a result, internists and other nononcology clinicians are routinely encountering immunotherapy patients who present with a remarkably wide range of symptoms. Here, we present the radiographic manifestations of common side effects from immunotherapy agents. An accurate diagnosis is critical in these often-complex clinical settings in which the consequences of the underlying cancer and other comorbidities must be distinguished from the variable manifestations of treatment toxicity.

Identification of nonalcoholic fatty liver disease following pancreatectomy for noninvasive intraductal papillary mucinous neoplasm.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) following pancreatectomy is a potential cause of long term morbidity in patients undergoing pancreatic resection with curative intent. Prior studies have reported an incidence of NAFLD up to 30% following pancreatectomy but the investigated cohorts were typically a mix of benign and malignant disease. Here we examined the incidence of NAFLD in a homogenous cohort of patients following pancreatectomy for benign intraductal papillary mucinous neoplasm (IPMN). METHODS: A retrospective review of patients who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post pancreatectomy CT/MRI scans were obtained as standard surveillance. We investigated changes in the liver parenchymal density on post surgical imaging to estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were performed. RESULTS: Our study cohort included 109 patients who underwent pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up was 52 months (range 8-130/months). The incidence of postoperative NAFLD was 17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and development of atrophy of the pancreas remnant were significant risk factors for development of hepatic steatosis (p < 0.05). CONCLUSION: Patients undergoing pancreatectomy for benign disease have a significant risk of developing NAFLD but the frequency is lower than previously reported in cohorts that included individuals with malignant disease. Highest risk was observed in individuals who underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further investigations to define the mechanisms that promote steatosis and interventions to prevent subsequent morbidity from NAFLD are warranted.

Progressive hypoventilation due to mixed CD8+ and CD4+ lymphocytic polymyositis following tremelimumab - durvalumab treatment.

BACKGROUND: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur. CASE PRESENTATION: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature. Serologic testing revealed a low level of de novo circulating antibodies against striated muscle fiber. Immunohistochemistry revealed type II muscle fiber atrophy with a mixed CD8+ and CD4+ lymphocyte infiltrate, indicative of inflammatory myopathy. CONCLUSIONS: This case supports the hypothesis that muscle tissue is a target for lymphocytic infiltration in immune checkpoint inhibitor-associated polymyositis. Further insights into the autoimmune mechanism of PM will hopefully contribute to the prevention and treatment of this phenomenon.

Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know.

Intravenous contrast is commonly used in noninvasive imaging procedures such as magnetic resonance imaging and computed tomography and can evaluate blood vessels and better characterize soft-tissue lesions. Although the incidence of adverse events after administration of contrast is low, it is important that clinicians and radiologists minimize risks and respond quickly and effectively when reactions occur. We will discuss a range of adverse events to iodinated and gadolinium-based contrast agents, including allergic-like reactions, nephrotoxicity, extravasation, and nephrogenic systemic fibrosis. We will review risk stratification for patients, as well as premedication and treatment of adverse events.

Cancer survivorship, a unique and growing cohort in medical practice: radiology perspective.

The unique medical and psychologic burdens of cancer survivorship have only recently been recognized. This rapidly expanding cohort of patients will be seen increasingly by non-oncology physicians who must consider medical issues related to their cancer or its therapy for any presenting symptoms. Appropriate use of clinical imaging is essential for diagnosing treatment-related complications, recurrent tumor, or emergence of second primaries. This article will review clinical imaging in common medical problems uniquely found in cancer survivors.