Identification and detection of microRNA kidney disease biomarkers in liquid biopsies.

PURPOSE OF REVIEW: MicroRNAs (miRNAs) are emerging rapidly as a novel class of biomarkers of major organ disorders, including kidney diseases. However, current PCR-based detection methods are not amenable to development for high-throughput, cost-effective miRNA biomarker quantification. RECENT FINDINGS: MiRNA biomarkers show significant promise for diagnosis and prognosis of kidney diseases, including diabetic kidney disease, acute kidney injury, IgA nephropathy and delayed graft function following kidney transplantation. A variety of novel methods to detect miRNAs in liquid biopsies including urine, plasma and serum are being developed. As miRNAs are functional transcripts that regulate the expression of many protein coding genes, differences in miRNA profiles in disease also offer clues to underlying disease mechanisms. SUMMARY: Recent findings highlight the potential of miRNAs as biomarkers to detect and predict progression of kidney diseases. Developing in parallel, novel methods for miRNA detection will facilitate the integration of these biomarkers into rapid routine clinical testing and existing care pathways. Validated kidney disease biomarkers also hold promise to identify novel therapeutic tools and targets. VIDEO ABSTRACT: http://links.lww.com/CONH/A43.

Myeloid Sarcoma: A Primer for Radiologists.

ABSTRACT: Myeloid sarcoma (MS) is a rare extramedullary neoplasm that can present in association with acute myeloid leukemia, most commonly in children younger than 15 years. This unique extramedullary malignancy may involve a variety of different organ systems and can present following, preceding, simultaneous with, or in insolation to acute myeloid leukemia. Common areas of extramedullary involvement include soft tissues, bones, lymph nodes, and the peritoneum. Imaging plays a critical role in the diagnosis and management of MS, with commonly used modalities including positron emission tomography-computed tomography, magnetic resonance imaging, computerized tomography, and ultrasound. The purpose of this review article is to provide radiologists with a comprehensive guide summarizing the relevant imaging and clinical features of MS, with emphasis on the role of imaging in the diagnosis, treatment, and follow-up of patients with MS. The relevant pathophysiology, epidemiology, clinical presentations, and differential diagnosis of MS will be reviewed. The relevance of different imaging modalities in diagnosis, monitoring of treatment response, and assessment of treatment-related complications will also be outlined. Through summarizing these topics, this review article aims to provide radiologists with a guide for understanding the existing knowledge of MS in the literature and the current role of imaging in the management of this unique malignancy.

Role of Radiologists in Contract Research Organizations (CROs).

Clinical trials play a vital role in advancing technology and novel therapies in the healthcare world. However, the increasing scale of trials and the complexity of the regulatory approval process is often a barrier for those interested in conducting research. Contract research organizations (CROs) aim to address this problem by offering their infrastructure and expertise to bring a therapy from conception to approval without the need for in-house staff. Clinical trial imaging often plays an essential role in this process, creating a need for radiologists and a unique opportunity to provide irreplaceable value in their ability to interpret and analyze the imaging outcomes of therapies in question. This paper explores the concept of CROs, the crucial role played by radiologists in their operation, and the nature of the CRO - radiologist relationship.

Abdominopelvic CT Imaging Findings in the Emergency Department in Patients With HIV Positive Status: Single Institute Experience.

OBJECTIVE: To assess emergency department (ED) abdominopelvic computed tomography (CT) imaging utilization and findings in patients with known human immunodeficiency virus (HIV) positive status. MATERIALS AND METHODS: A retrospective chart review of imaging, clinical, and laboratory data was performed for HIV positive patients who demonstrated HIV-related findings on abdominopelvic CT imaging performed within the ED. RESULTS: One hundred and eighty-eight patients with 522 CT scans of the abdomen and/or pelvis were reviewed. 47 patients with HIV presenting to the ED on 82 separate occasions were included in this study (mean age 43.3 years). Patients presented to the ED with infectious/inflammatory disease (n = 54) or history of HIV-related malignancy or new/worsening HIV-related malignancy (n = 28). The most common findings on abdominopelvic CT were anorectal pathology including anorectal abscess or proctitis (n = 22), followed by colitis (n = 19). Findings of HIV-associated malignancy were less common, including anal/rectal cancer (n = 7), Kaposi's sarcoma (n = 4), and lymphoma (n = 2). At the time of ED visit, 25.6% (n = 21) of patients had acquired immunodeficiency syndrome (AIDS). Higher WBC counts were found in the infectious/inflammatory group (P = 0.021) and patients without AIDS (P = 0.0159), while lower WBC counts were associated with new or worsening malignancy (P = 0.007) and AIDS (P = 0.0000). Patients with AIDS were more likely to be deceased at the time of our study. CONCLUSIONS: The majority of ED visits within our population were attributed to infectious/inflammatory etiologies. CT findings demonstrated predominantly infectious/inflammatory processes, with anorectal pathology being the most common. Findings of malignancy on CT were less common, while opportunistic infections and AIDS-defining malignancies were uncommon.

Chest CT Findings in Patients with HIV Presenting to the Emergency Department: A Single Institute Experience.

PURPOSE: The aim of this study was to analyze chest CT imaging findings and relevant clinical factors in patients with HIV presenting to the emergency department (ED). MATERIALS AND METHODS: A retrospective review was performed to identify patients with HIV who received chest CT imaging evaluation in the acute ED setting. Analyzed patients included adults with a known diagnosis of HIV who presented to the ED at a single tertiary care center between 2004 and 2020 and received chest CT imaging. Chest CT findings were assessed by 2 radiologist readers, and relevant clinical data were gathered. Statistical analysis was performed to determine if imaging and clinical factors demonstrate significant associations with CD4 count, viral load, and antiretroviral therapy status. RESULTS: A total of 113 patients with HIV were identified who presented to the ED and underwent chest CT imaging evaluation (mean age 47 ± 11 years). Frequently detected chest CT findings included infectious pneumonia (24%), malignancy (11%), pleural effusion (17%), pericardial effusion (13%), and pulmonary embolism (4%). CD4 count, viral load, and active retroviral therapy demonstrated statistically significant associations with a number of key imaging and clinical factors, including presence of pneumonia, malignancy, average length of hospital admission, and survival. CONCLUSION: Patients with HIV present with a wide range of imaging findings when presenting in the acute ED setting. CD4 count, viral load, and active retroviral therapy status demonstrate statistically significant associations with multiple key imaging findings and clinical factors. Chest CT plays an integral role in the clinical management of this unique patient population.

Evaluating the Downstream Revenues of a Self-Pay Bi-Parametric Prostate MRI Program.

OBJECTIVE: To quantify downstream healthcare utilization and revenue associated with a self-pay bi-parametric prostate MRI (bpMRI) program. METHODS: Medical records of 592 patients who underwent bpMRI between August 2017 and March 2020 were examined for follow-up clinical activities. These include prostate biopsy, radical prostatectomy, external beam radiation therapy, brachytherapy, androgen deprivation therapy, CT Chest, Abdomen and Pelvis, PET/CT, MRI Pelvis, and Nuclear Medicine Bone Scans. The charges for each clinical activity were derived from the Medicare Physician Fee Schedule to conservatively estimate revenues. This patient population was further divided into four groups: Group A, patients who demonstrated an MRI lesion and underwent prostatectomy; Group B, patients who did not demonstrate lesion but underwent prostatectomy; Group C, patients who demonstrated lesion but did not undergo prostatectomy; and Group D, patients who neither demonstrated lesion nor underwent prostatectomy. Revenues for each group were categorized by Urology, Radiation Oncology and Radiology subspecialties. RESULTS: Conservative estimates yielded $520 of downstream revenue per patient who underwent bpMRI. Group A patients yielded 47% of total revenue ($1974 per patient). Group B patients, the smallest group, yielded $1828 per patient. Group C patients made up the largest group and grossed $398 per patient. Group D demonstrated the lowest per patient revenue of $179. Groups A and B yielded most relative revenue for Urology. Group C yielded most relative revenue for Radiation Oncology, and Group D yielded most relative revenue for Radiology. CONCLUSION: A self-pay bpMRI program has the potential to improve patient access to prostate cancer screening while remaining financial sustainable.

A Decade of Success in Melanoma Immunotherapy and Targeted Therapy: What Every Radiologist Should Know.

ABSTRACT: Treatment strategies for malignant melanoma have rapidly evolved over the past decade. Because of its propensity to develop advanced stage and metastatic disease, melanoma has contributed to the majority of mortalities among patients with skin cancer. The development of novel therapeutics such as immunotherapy and targeted molecular therapies has revolutionized the treatment of patients with advanced stage and metastatic malignant melanoma. Immune checkpoint inhibitors, BRAF/MEK inhibitors, and other revolutionary therapies have demonstrated remarkable success in the treatment of this common malignancy. Along with these advancements in systemic therapies, imaging has continued to play a critical role in the diagnosis and follow-up of patients with malignant melanoma. As the use of these novel therapies continues to expand, knowledge of the evolving therapeutic landscape of melanoma is becoming critical for radiologists. In this review, we provide a primer for radiologists outlining the evolution of immunotherapy and targeted therapy in the treatment of melanoma. We discuss the critical role of imaging in evaluation of treatment response, including a summary of current imaging response guidelines. Last, we summarize the essential role of imaging in the evaluation of potential adverse events seen in patients with malignant melanoma undergoing treatment with immune checkpoint inhibitors.

Anorectal pathology in the HIV population: a guide for radiologists.

Patients with human immunodeficiency virus (HIV) can present with a wide range of different acute and chronic pathologies. Anorectal conditions are particularly common in this unique patient population, including pathologies, such as proctitis, anorectal abscess, anorectal fistula, and anal squamous cell carcinoma. The radiologist plays a critical role in the assessment of these common forms of anorectal disease, as these conditions can present with various findings on imaging assessment. Pelvic CT, MRI, and FDG-PET/CT are among the most common modalities used for assessment of anorectal disease in the HIV patient population. Knowledge of the fundamental clinical and imaging findings associated with these pathologies in HIV patients is critical for radiologists.

Primary peritoneal serous carcinoma: a primer for radiologists.

Primary peritoneal serous carcinoma (PPSC) is a rare primary peritoneal tumor characterized by a unique range of clinical features and imaging findings. Though it shares many clinical, histologic, and imaging features with serous ovarian carcinoma, it remains a distinct clinical entity. Although less common than its primary ovarian counterpart, PPSC is characterized by a prognosis that is often equally poor with presentations common in late stages of disease. Key imaging modalities used in the evaluation of PPSC include ultrasound, CT, MRI, and PET/CT. For radiologists, an understanding of the pertinent imaging findings, pathologic correlations, and clinical features of PPSC is essential for arriving at the correct diagnosis and guiding the subsequent appropriate management of this complex malignancy.

Imaging-based Toxicity and Response Pattern Assessment Following CAR T-Cell Therapy.

Background Chimeric antigen receptor (CAR) T-cell immunotherapy is increasingly used for refractory lymphoma but may lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Imaging may assist in clinical management. Associations between CRS or ICANS grade and imaging findings remain not fully established. Purpose To determine associations between imaging findings and clinical grade of CRS or ICANS, evaluate response patterns, and assess imaging use following CAR T-cell treatment. Materials and Methods Patients with refractory B-cell lymphoma who received CAR T-cell infusion between 2018 and 2020 at a single center were analyzed retrospectively. Clinical CRS or ICANS toxicity grade was assessed using American Society for Transplantation and Cellular Therapy, or ASTCT, consensus grading. Thoracic and head images (radiographs, CT scans, MRI scans) were evaluated. Associations between imaging findings and clinical CRS or ICANS grade were analyzed. Wilcoxon signed-rank and χ2 tests were used to assess associations between thoracic imaging findings, clinical CRS toxicity grade, and imaging-based response. Response to therapy was evaluated according to Deauville five-point scale criteria. Results A total of 38 patients (mean age ± standard deviation, 59 years ± 10; 23 men) who received CAR T-cell infusion were included. Of these, 24 (63% [95% CI: 48, 79]) and 11 (29% [95% CI: 14, 44]) experienced clinical grade 1 or higher CRS and ICANS, respectively. Patients with grade 2 or higher CRS were more likely to have thoracic images with abnormal findings (10 of 14 patients [71%; 95% CI: 47, 96] vs five of 24 patients [21%; 95% CI: 4, 37]; P = .002) and more likely to have imaging evidence of pleural effusions (five of 14 [36%; 95% CI: 10, 62] vs two of 24 [8.3%; 95% CI: 0, 20]; P = .04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; P = .048). Positive imaging findings were identified in three of seven patients (43%) with grade 2 or higher ICANS who underwent neuroimaging. The best treatment response included 20 of 36 patients (56% [95% CI: 39, 72]) with complete response, seven of 36 (19% [95% CI: 6, 33]) with partial response, one of 36 (2.8% [95% CI: 0, 8]) with stable disease, and eight of 36 (22% [95% CI: 8, 36]) with progressive disease. Conclusion Thoracic imaging findings, including pleural effusions and atelectasis, correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. CAR T-cell therapy yielded high response rates. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Langer in this issue.

The modern therapeutic & imaging landscape of metastatic prostate cancer: a primer for radiologists.

Prostate cancer represents one of the leading causes of cancer-related mortality in the United States and the most common cancer among men. Treatment paradigms for the management of advanced stages of prostate cancer have continued to evolve in recent years. These advancements in the therapeutic landscape of metastatic prostate cancer and diagnostic imaging modalities have fundamentally changed the treatment of patients with prostate cancer. In this review article we provide a primer for radiologists highlighting the most recent developments in treatment options and imaging techniques utilized in the modern oncologic management of metastatic prostate cancer. We will examine current therapy options and associated toxicities with an emphasis on relevant imaging findings commonly encountered by radiologists. We also summarize the role of modalities including CT, MRI, PET, bone scintigraphy, and PET in the diagnosis and follow-up of patients with metastatic prostate cancer.

Clinically Significant Prostate Cancer Detection After a Negative Prebiopsy MRI Examination: Comparison of Biparametric Versus Multiparametric MRI.

BACKGROUND. The frequency of clinically significant prostate cancer (csPCa) following negative biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) has not been well investigated in direct comparative studies. OBJECTIVE. The purposes of this study were to compare the frequency of csPCa after negative prebiopsy bpMRI and mpMRI and to evaluate factors predictive of csPCa in the two cohorts. METHODS. This retrospective study included 232 men (mean age, 64.5 years) with negative bpMRI from August 2017 to March 2020 and 193 men (mean age, 69.0 years) with negative mpMRI from January 2018 to December 2018. PI-RADS category 1 or 2 was defined as negative. The study institution offered bpMRI as a low-cost self-pay option for patients without insurer coverage of prebiospy mpMRI. Patient characteristics and subsequent biopsy results were recorded. CsPCa was defined as Gleason score of 3 + 4 or greater. Multivariable regression analyses were performed to identify independent predictors of csPCa. The AUC of PSA density (PSAD) for csPCA was computed, and the diagnostic performance of PSAD was assessed at a clinically established threshold of 0.15 ng/mL2. RESULTS. Systematic biopsy was performed after negative bpMRI for 41.4% (96/232) of patients and after negative mpMRI for 30.5% (59/193) (p = .02). Among those undergoing biopsy, csPCa was present in 15.6% (15/96) in the bpMRI cohort versus 13.6% (8/59) in the mpMRI cohort (p = .69). The NPV for csPCa was 84% (81/96) for bpMRI and 86% (51/59) for mpMRI. In multivariable analyses, independent predictors of csPCa included smaller prostate volume (OR, 0.27; p < .001) and greater PSAD (OR, 3.09; p < .001). In multivariable models, bpMRI (compared with mpMRI) was not independently predictive of csPCa (p > .05). PSAD had an AUC for csPCa of 0.71 (95% CI, 0.56-0.87) in the bpMRI cohort versus 0.68 (95% CI, 0.42-0.93) in the mpMRI cohort. For detecting csPCa, a PSAD threshold of 0.15 ng/mL2 had NPV of 90% and PPV of 28%, in the bpMRI cohort versus NPV of 92% and PPV of 44% in the mpMRI cohort. CONCLUSION. The frequencies of csPCa were not significantly different at systematic biopsy performed after negative bpMRI and mpMRI examinations. PSAD had similar diagnostic utility for csPCa in the two cohorts. CLINICAL IMPACT. Either bpMRI or mpMRI, in combination with PSAD measurement, can help avoid negative prostate biopsies.

Past, Present, and Future of Serum Tumor Markers in Management of Ovarian Cancer: A Guide for the Radiologist.

The ability to accurately detect early ovarian cancer and subsequently monitor treatment response is essential to improving survival for patients with ovarian malignancies. Several serum tumor markers (STMs)-including cancer antigen 125 (CA-125), human epididymis protein 4 (HE4), cancer antigen 19-9 (CA 19-9), and carcinoembryonic antigen (CEA)-have been used as a noninvasive method of identifying ovarian cancer in conjunction with imaging. Although current guidelines do not recommend use of STMs as screening tools for ovarian cancer, these markers have clinical utility in both diagnosis and surveillance for women with ovarian cancer. CA-125 is the most commonly used STM; its level may be elevated in several types of ovarian cancer, including epithelial cell tumors, carcinosarcoma, teratomas, and secondary ovarian malignancies. An elevated level of CA 19-9 is associated with clear cell tumors, teratomas, and secondary malignancies. CEA is most commonly associated with mucinous ovarian cancers. Finally, HE4 is being increasingly used to identify certain subtypes of epithelial ovarian cancers, particularly serous and endometrioid tumors. Diagnosis of ovarian cancers relies on a combination of CA-125 levels and US findings, which include a large adnexal mass or high-risk features, including septa and increased vascularity. CT is preferred for staging and is used along with PET and STM monitoring for surveillance. Increasingly, MRI is being used to characterize ovarian lesions that are indeterminate at US or CT. The future of STM testing involves development of "liquid biopsies," in which plasma samples are analyzed for evidence of tumors, including circulating tumor DNA or tumor cells and tumor micro-RNA. When combined with traditional imaging techniques, liquid biopsies may lead to earlier diagnosis and improved survival. An invited commentary by Shinagare is available online. ©RSNA, 2021.

COVID-19 infection in the cancer population: a study of emergency department imaging utilization and findings.

PURPOSE: To analyze emergency department (ED) computerized tomography (CT) utilization in cancer patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective chart review was performed to identify cancer patients who received COVID-19 diagnosis within the single healthcare system and presented to the ED within 30 days of COVID-19 positive date between May 1 and December 31, 2020. RESULTS: In our 61 patients, the mean age was 72.5 years old, with 34% of patients (n = 21) on active cancer therapy and 66% (n = 40) on surveillance only. Most patients (n = 53) received their COVID-19 diagnosis within the ED, with 8 patients diagnosed prior to initial ED visit. The most common CT studies ordered within the ED were CT chest (n = 25), CT abdomen/pelvis (A/P) (n = 20), CT head (n = 8), and CT chest/abdomen/pelvis (C/A/P) (n = 7). COVID-19 findings were present on 33 scans, findings of worsening malignancy on 12 scans, and non-COVID non-cancer findings on 9 scans. Significant differences in CT severity score (p = 0.0001), indication for hospitalization (p = 0.026), length of hospitalization (p = 0.004), interventions (remdesivir, mechanical ventilation, and vasopressor support) while hospitalized (p < 0.05), and mortality (p = 0.042) were found between the prior diagnosis and ED diagnosis groups. No such differences were found between the active treatment and surveillance groups. CONCLUSION: ED CT imaging findings in patients with cancer and COVID-19 are predominantly related to COVID-19 infection, rather than cancer history or anti-cancer therapy status.

Overview of serum and tissue markers in colorectal cancer: a primer for radiologists.

Serum and tissue tumor markers provide crucial information in the diagnosis, treatment, and follow-up of colorectal cancers. Tissue tumor markers are increasingly used for determination of targeted chemotherapy planning based on genotyping of tumor cells. Recently, plasma-based technique of liquid biopsy is being evaluated for providing tumor biomarkers in the management of colorectal cancer. Tumor markers are commonly used in conjunction with imaging during initial staging, treatment determination, response assessment, and determination of recurrence or metastatic disease. Knowledge of tumor markers and their association with radiological findings is thus crucial for radiologists. Additionally, various novel imaging techniques are being evaluated as potential noninvasive imaging biomarkers to predict tumor genotypes, features, and tumor response. We review and discuss the potential role of these newer imaging techniques.

The Past, Present, and Future (Liquid Biopsy) of Serum Tumor Markers in Lung Cancer: A Primer for the Radiologist.

ABSTRACT: Lung cancer continues to be a major cause of death throughout the world. The ability to both accurately diagnose lung cancer in its early stages and monitor response to treatment is essential to reducing the morbidity and mortality associated with the disease. Serum tumor markers have been identified as potential biomarkers that may aid in lung cancer diagnosis and surveillance. These markers, when combined with cross-sectional imaging, may result in more robust screening and surveillance protocols. The future role of serum tumor markers in lung cancer includes the advancement of "liquid biopsies," in which peripheral blood samples are analyzed for tumor components without the need for a tissue biopsy.

Posttransplant Lymphoproliferative Disorder Status Post-Solid Organ Transplant Presenting to the Emergency Department: Single Institute Experience.

OBJECTIVE: The objective of this study was to evaluate the clinical, laboratory, imaging, and pathology findings associated with emergency department presentations of posttransplant lymphoproliferative disorder (PTLD) after solid organ transplant (SOT). METHODS: Fifteen patients presenting to a single tertiary care center between 2004 and 2019 with PTLD after SOT were identified from a pathology database. Twelve patients presenting through the emergency department were included in the study. Demographic, clinical, imaging, pathology, treatment, and outcome data were reviewed. RESULTS: Among this 12 patient cohort (7 men; mean age, 44.2 years), transplant history included 4 combined kidney/pancreas, 4 kidney, 2 liver, 1 cardiac, and 1 lung. Mean time from transplant to diagnosis was 7.6 years. Posttransplant lymphoproliferative disorder was identified on initial computed tomography scans in 10 of 12 patients. The most common sites for PTLD development were the gastrointestinal tract (4/12) and liver (3/12). Outcomes included resolution of PTLD in 9 of 12 patients, with 3 patients dying within 6 months of diagnosis. CONCLUSIONS: Posttransplant lymphoproliferative disorder is a serious consequence of solid organ transplantation that can present in various locations and with varied symptomatology in the emergency setting. Other posttransplant complications may present similarly including chronic rejection and infection. Posttransplant lymphoproliferative disorder should be considered in SOT patients presenting with worsening abdominal pain or constitutional symptoms, even with normal laboratory workup.

Imaging features of hypercalcemia: A primer for emergency radiologists.

Hypercalcemia is a marker for a wide variety of underlying etiologies, and its presentation in the emergency setting may be asymptomatic, incidental, or a primary complaint with associated symptoms and physical exam findings. While the workup is initially driven through serum laboratory testing, imaging plays an important role in diagnosis and post-treatment follow up. This review covers multiple common and uncommon etiologies of hypercalcemia, details their underlying mechanisms, and identifies the most important associated imaging findings. It is important for radiologists to be familiar with these etiologies and imaging findings, particularly in the emergency setting since hypercalcemia may represent the only significant laboratory abnormality associated with the presenting condition. Furthermore, the radiologist's interpretation of a study may be directly influenced by knowing about a patient's hypercalcemia.

CAR T-Cell Therapy: An Update for Radiologists.

Chimeric antigen receptor-engineered (CAR) T-cell therapy is a promising novel immunotherapy that has the potential to revolutionize cancer treatment. Four CAR T-cell therapies have received FDA approval within the last 5 years, and the role of CAR T cells is anticipated to continue to evolve and expand. However, various aspects of CAR T-cell therapies remain poorly understood, and the therapies are associated with severe side effects, including cytokine release syndrome and immune effector cell-associated neurotoxicity, which require prompt diagnosis and intervention. The purposes of this review are to describe the role of imaging in diagnosing and monitoring toxicities from CAR T-cell therapies and explore the use of various imaging techniques, including PET/CT with novel radiotracers, to predict and assess treatment response and adverse effects. It is important for radiologists to recognize the imaging findings associated with each syndrome and to recognize the typical and atypical treatment response patterns associated with CAR T-cell therapy. Given the expected increase in use of CAR T cells in the near future, radiologists should familiarize themselves with the imaging findings encountered in these novel therapies so that they can provide comprehensive and up-to-date guidance for clinical management.