MRI features of treated hepatocellular carcinoma following locoregional therapy: a pictorial review.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide and within the United States. Liver transplant or partial liver resection is the definitive treatment of choice for HCC; however, the majority of cases are detected in advanced stages due to its early-stage asymptomatic nature, often precluding surgical treatment. Locoregional therapy plays an essential role in HCC management, including curative intent, as a bridge to transplant, or in some cases palliative therapy. Radiologists play a critical role in assessing tumor response following treatment to guide further management that may potentially impact transplantation eligibility; therefore, it is important for radiologists to have an understanding of different locoregional therapies and the variations of imaging response to different therapies. In this review article, we outline the imaging response to ablative therapy (AT), transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), and stereotactic body radiation therapy (SBRT). We will also briefly discuss the basic concepts of these locoregional therapies. This review focuses on the imaging features following locoregional treatment for hepatocellular carcinoma following AT, TACE, SIRT, and SBRT.

A radiologist's guide to novel anticancer therapies in the era of precision medicine.

Novel anticancer agents have replaced conventional chemotherapy as first line agents for many cancers, with continued new and expanding indications. Small molecule inhibitors act on cell surface or intracellular targets and prevent the downstream signaling that would otherwise permit tumor growth and spread. Anticancer antibodies can be directed against growth factors or may be immunotherapeutic agents. The latter act by inhibiting mechanisms that cancer cells use to evade the immune system. Hormonal agents act by decreasing levels of hormones that are necessary for the growth of certain cancer cells. Cancer therapy protocols often include novel anticancer agents and conventional chemotherapy used successively or in combination, in order to maximize survival and minimize morbidity. A working knowledge of anti-cancer drug classification will aid the radiologist in assessing response on imaging.

Outcomes of Positive and Suspicious Findings in Clinical Computed Tomography Lung Cancer Screening and the Road Ahead.

Rationale: Future optimization of computed tomography (CT) lung cancer screening (CTLS) algorithms will depend on clinical outcomes data. Objectives: To report the outcomes of positive and suspicious findings in a clinical CTLS program. Methods: We retrospectively reviewed results for patients from our institution undergoing lung cancer screening from January 2012 through December 2018, with follow-up through December 2019. All exams were retrospectively rescored using Lung-RADS v1.1 (LR). Metrics assessed included positive, probably benign, and suspicious exam rates, frequency/nature of care escalation, and lung cancer detection rates after a positive, probably benign, and suspicious exam result and overall. We calculated time required to resolve suspicious exams as malignant or benign. Results were broken down by subcategories, reason for positive/suspicious designation, and screening round. Results: During the study period 4,301 individuals underwent a total of 10,897 exams. The number of positive (13.9%), suspicious (5.5%), and significant incidental (6.4%) findings was significantly higher at baseline screening. Cancer detection and false-positive rates were 2.0% and 12.3% at baseline versus 1.3% and 5.1% across subsequent screening rounds, respectively. Baseline solid nodule(s) 6 to <8 mm were the only probably benign findings resulting in lung cancer detection within 12 months. New solid nodules 6 to <8 mm were the only LR category 4A (LR4A) findings falling within the LR predicted cancer detection range of 5-15% (12.8%). 38.5% of LR4A cancers were detected within 3 months. Conclusions: Modification of the definition and suggested workup of positive and suspicious lung cancer screening findings appears warranted.

Intracranial, intradural aneurysmal bone cyst.

Aneurysmal bone cysts (ABCs) are benign, expansile, blood-filled, osteolytic lesions with internal septations that may be intraosseous or extraosseous. The cysts may cause local mass effect, and changes in the regional vascular supply necessitating intervention. A case of an intracranial, intradural ABC in a young male patient with progressively severe headaches is presented. This is only the third recorded intradural case, the majority of these rare lesions being extracranial and only a minute fraction intracranial.

CT findings in adult celiac disease.

Celiac disease is now recognized as a common disease, occurring in about one in every 200 Americans. However, less than 10% of cases are currently diagnosed, with a diagnostic delay of more than 10 years from onset of symptoms. In the past, barium examination of the small bowel demonstrated a pattern of abnormal findings caused by the pathophysiologic changes induced by malabsorption, thus leading to diagnosis of celiac disease and other diseases of malabsorption. Although not specific, that pattern prompted further patient evaluation. The number of barium examinations performed and the skill necessary to interpret their results are both in decline. Abdominal pain in celiac disease is a common early complaint that often leads to computed tomography (CT). Improved CT resolution now permits better depiction of the small bowel, colon, and mesenteric lymph nodes, all of which are affected by celiac disease. Detection of celiac disease with CT will allow treatment to be initiated to prevent the significant morbidity and increased mortality associated with a delay in diagnosis. The abnormal CT findings seen over the past decade during review of more than 200 cases of celiac disease demonstrate that CT depicts more features of celiac disease than did barium examination. Pattern recognition for the diagnosis of small bowel diseases that create structural changes in the bowel wall is well accepted. Because it demonstrates features of celiac disease not detected with barium examination, CT may be more sensitive than barium examination for diagnosis of this disease.

Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.

Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section. (125)I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.

Update on prostate imaging.

Successful and accurate imaging of prostate cancer is integral to its clinical management from detection and staging to subsequent monitoring. Various modalities are used including ultrasound, computed tomography, and magnetic resonance imaging, with the greatest advances seen in the field of magnetic resonance.

Restoration of skeletal muscle ischemia-reperfusion injury in humanized immunodeficient mice.

BACKGROUND: Ischemia and reperfusion (I/R) of tissue provokes an inflammatory process that is highly dependent on circulating natural immunoglobulin M (IgM) and the complement cascade. In mice, a single IgM specificity produced by peritoneal B cells can initiate reperfusion injury. It is unknown whether humans express natural IgM with a similar specificity. It is also unknown whether pathogenic IgM is produced solely from peritoneal B cells or can also be made by circulating B cells. METHODS: Immunodeficient mice lacking endogenous immunoglobulin were used. Mice were reconstituted with 0.9% normal saline, human serum, or xenografted human peripheral blood lymphocytes (PBLs) and then subjected to tourniquet-induced hindlimb I/R. Serum human IgM and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent (ELISA) assay. Skeletal muscle was harvested for injury assessment by histology and for immunohistochemistry. RESULTS: Immunodeficient mice were protected from skeletal muscle injury after hindlimb I/R. Transfer of human serum restored skeletal muscle damage. Rag2/gammaR-/- mice that were engrafted with human PBL (huPBL-SCID) had high levels of human IgM. huPBL-SCID mice developed significantly more skeletal muscle injury than control saline-treated mice (P < or = .01) and human serum-reconstituted Rag2/gammaR-/- mice (P < or = 0.01). Sham-treated huPBL-SCID mice had no muscle injury, demonstrating that human lymphocyte engraftment did not cause injury in the absence of ischemia. Deposition of human IgM was observed on injured but not sham-injured muscle. CONCLUSION: Human serum can initiate murine skeletal muscle I/R injury. Circulating human PBL may be a source of pathogenic IgM. The huPBL-SCID mouse may be a useful model to define the specificity of pathogenic human IgM and to test therapeutics for I/R injury.

Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM.

BACKGROUND: The injury sustained by reperfused skeletal muscle is inflammatory and is initiated by binding of pre-formed IgM to involved tissue, followed by local complement activation and further inflammation. A clone of natural IgM has been described that initiates this injury, suggesting that specific antigens are exposed on ischemic tissues that act as ligands for this pathogenic antibody. In these experiments, we examine the properties of short peptide sequences, and their homologues, that bind to the antigen-combining site of this pathogenic IgM clone. METHODS: A 12-mer phage display library was biopanned with the pathogenic IgM clone and then negatively selected against an inactive natural IgM clone. All 8 clones that bound specifically to the pathogenic IgM had closely related amino acid sequences. P8 is the clone that bound most avidly. Tissue lysates from ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non-muscle myosin as the protein reacting with pathogenic antibody in ischemic gut and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers homologues that are contained within non-muscle myosin and glycogen phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups receiving saline, P8, N2, GP1, or a random peptide at the start of the experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia and 3 hours of reperfusion. Muscle was assessed for injury with histology and for immune activation with histochemistry. RESULTS: Intravenous administration of P8, N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a random peptide (22 +/- 2.3), P less than .05. This level of protection from injury is comparable to that seen in the absence of antibody altogether. As well, P8-treated animals exhibited a marked decrease in deposition of IgM (as well as C3) in comparison to saline treated controls. CONCLUSIONS: Specific peptide blockade of an injury-inducing IgM clone decreased the local consequences of skeletal muscle ischemia/reperfusion injury in wild-type animals that have the full repertoire of IgM specificities. This indicates that the antibodies that initiate reperfusion injury have specificity only for P8-related antigens. This could also indicate that the variety of relevant ischemic antigens is quite restricted.

Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle.

Ischemia with subsequent reperfusion (IR) injury is a significant clinical problem that occurs after physical and surgical trauma, myocardial infarction, and organ transplantation. IR injury of mouse skeletal muscle depends on the presence of both natural IgM and an intact C pathway. Disruption of the skeletal muscle architecture and permeability also requires mast cell (MC) participation, as revealed by the fact that IR injury is markedly reduced in c-kit defective, MC-deficient mouse strains. In this study, we sought to identify the pathobiologic MC products expressed in IR injury using transgenic mouse strains with normal MC development, except for the lack of a particular MC-derived mediator. Histologic analysis of skeletal muscle from BALB/c and C57BL/6 mice revealed a strong positive correlation (R(2) = 0.85) between the extent of IR injury and the level of MC degranulation. Linkage between C activation and MC degranulation was demonstrated in mice lacking C4, in which only limited MC degranulation and muscle injury were apparent. No reduction in injury was observed in transgenic mice lacking leukotriene C(4) synthase, hemopoietic PGD(2) synthase, N-deacetylase/N-sulfotransferase-2 (enzyme involved in heparin biosynthesis), or mouse MC protease (mMCP) 1. In contrast, muscle injury was significantly attenuated in mMCP-5-null mice. The MCs that reside in skeletal muscle contain abundant amounts of mMCP-5 which is the serine protease that is most similar in sequence to human MC chymase. We now report a cytotoxic activity associated with a MC-specific protease and demonstrate that mMCP-5 is critical for irreversible IR injury of skeletal muscle.