This copy is for personal use only. To order printed copies, contact reprints@rsna.org I n P r e s s Abbreviations: ICU = intensive care unit; ACE2 = angiotensin converting enzyme 2; COVID-19 = Coronavirus disease 2019; RUQ = right upper quadrant; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2.Key Results: -33% of inpatients with COVID-19 had abdominal imaging and 17% had cross-sectional imaging. Imaging was associated with age (OR 1.03 per year increase) and intensive care unit (ICU) admission (OR 17.3). -54% of right upper quadrant ultrasounds demonstrated findings of cholestasis. -31% of CTs showed bowel wall abnormalities. Signs of late ischemia were seen on 20% of CTs in ICU patients (2.7% of ICU patients), with pathologic correlation suggesting small vessel thrombosis. Summary Statement: Bowel abnormalities, including ischemia, and cholestasis were common findings on abdominal imaging of inpatients with COVID-19. I n P r e s s Abstract:Background: Angiotensin converting enzyme 2 (ACE2), a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury.Purpose: To report abdominal imaging findings in patients with coronavirus disease 2019 . Materials and Methods:In this retrospective cross-sectional study, patients consecutively admitted to a single quaternary care center from 3/27/2020 to 4/10/2020 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included. Abdominal imaging studies performed in these patients were reviewed and salient findings recorded.Medical records were reviewed for clinical data. Univariable analysis and logistic regression were performed. Results: 412 patients (average age 57 years; range 18->90 years; 241 men, 171 women) were evaluated. 224 abdominal imaging studies were performed (radiographs, n=137; ultrasound, n=44; CT, n=42; MRI, n=1) in 134 patients (33%). Abdominal imaging was associated with age (odds ratio [OR] 1.03 per year increase, p=0.001) and ICU admission (OR 17.3, p<0.001). Bowel wall abnormalities were seen on 31% of CT scans (13 of 42) and were associated with ICU admission (OR 15.5, p=0.01). Bowel findings included pneumatosis or portal venous gas, seen on 20% of CT scans in ICU patients (4 of 20). Surgical correlation (n=4) revealed unusual yellow discoloration of bowel (n=3) and bowel infarction (n=2). Pathology demonstrated ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles (n=2). Of right upper quadrant ultrasounds, 87% (32 of 37) were performed for liver laboratory findings, and 54% (20 of 37) demonstrated a dilated sludge-filled gallbladder suggestive of cholestasis. Patients with a cholecystostomy tube placed (n=4) had negative bacterial cultures. Conclusion: Bowel abnormalities and cholestasis were common findings on abdominal imaging of inpatients with COVID-19. Patients who went to laparotomy often had ischemia, possibly due to sma...
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases. Serial analysis of cfDNA demonstrated multiple recurrent point mutations in the FGFR2 kinase domain at progression. Accordingly, biopsy of post-progression lesions and rapid autopsy revealed marked inter- and intra-lesional heterogeneity, with different FGFR2 mutations in individual resistant clones. Molecular modeling and in vitro studies indicated that each mutation lead to BGJ398 resistance and was surmountable by structurally distinct FGFR inhibitors. Thus, polyclonal secondary FGFR2 mutations represent an important clinical resistance mechanism that may guide development of future therapeutic strategies.
Cancer cachexia and sarcopenia can occur frequently in patients with advanced cancer, and may negatively affect treatment outcomes. This article highlights the importance of assessing sarcopenia and describes the relationship between sarcopenia and patients' quality of life in patients with newly diagnosed, incurable cancer.
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