Pseudocirrhosis: A Case Series with Clinical and Radiographic Correlation and Review of the Literature.

BACKGROUND AND AIMS: Pseudocirrhosis is a poorly understood acquired morphologic change of the liver that occurs in the setting of metastatic malignancy and radiographically resembles cirrhosis. Pseudocirrhosis has been primarily described in metastatic breast carcinoma, with few case reports arising from other primary malignancies. We present 29 cases of pseudocirrhosis, including several cases from primary malignancies not previously described. METHODS: Radiologic, clinical, demographic, and biomedical data were collected retrospectively and analyzed. We compared clinical and radiologic characteristics and outcomes between patients with pseudocirrhosis arising in metastatic breast cancer and non-breast primary malignancies. RESULTS: Among the 29 patients, 14 had breast cancer and 15 had non-breast primaries including previously never reported primaries associated with pseudocirrhosis, melanoma, renal cell carcinoma, appendiceal carcinoid, and cholangiocarcinoma. Median time from cancer diagnosis to development of pseudocirrhosis was 80.8 months for patients with primary breast cancer and 29.8 months for non-breast primary (p = 0.02). Among all patients, 15 (52%) had radiographic features of portal hypertension. Radiographic evidence of portal hypertension was identified in 28.6% of breast cancer patients, compared to 73.3% of those with non-breast malignancies (p = 0.03). CONCLUSION: Pseudocirrhosis has most commonly been described in the setting of metastatic breast cancer but occurs in any metastatic disease to the liver. Our study suggests that portal hypertensive complications are more common in the setting of non-breast primary cancers than in metastatic breast cancer. Prior exposure to multiple chemotherapeutic agents, and agents known to cause sinusoidal injury, is a common feature but not essential for the development of pseudocirrhosis.

Management Impact of Metachronous Oligometastatic Disease Identified on 18F-Fluciclovine (Axumin™) PET/CT in Biochemically Recurrent Prostate Cancer.

PURPOSE: We assessed the incidence rate and management impact of oligometastatic disease detected on 18F-fluciclovine (Axumin™) PET/CT in men with first biochemical recurrence (BCR) of prostate cancer (PCA) after definitive primary therapy. METHODS AND MATERIALS: We retrospectively reviewed our clinical database for men with PCA who underwent 18F-fluciclovine PET/CT for imaging evaluation of BCR with negative or equivocal findings on conventional imaging. We included patients with up to and including 5 metastases (oligometastases) regardless of imaging evidence for local recurrence in the treated prostate bed. We examined the association between mean serum prostate specific antigen (PSA) levels with the number of oligometastases (non-parametric ANOVA) and between patients with or without local recurrence (Student t-test). The management impact of oligometastatic disease was tabulated. RESULTS: We identified 21 patients with oligometastases upon first BCR (PSA 0.2-56.8 ng/mL) out of 89 eligible patients. There was a significant difference (p = 0.04) in the mean PSA levels between patients with local recurrence (n = 12) and those without local recurrence (n = 9). In the subgroup of analysis of patients without local recurrence, there was no significant association between mean PSA level and number of oligometastases (p = 0.83). Distribution of oligometastases included 66.7% isolated nodal disease and 33.3% bone only. Twelve (57.1%) patients had change in management to include change in ADT, salvage therapy, or both. Treatment change was initiated in 62.5%, 28.6%, 66.7%, 100%, and 100% of patients with 1, 2, 3, 4, and 5 oligometastatic lesions, respectively. CONCLUSION: The incidence rate of oligometastatic disease in men with first BCR of PCA undergoing 18F-fluciclovine PET/CT for imaging evaluation of BCR was 23.6% in our eligible patient population. There was no significant association between serum PSA level and the number of oligometastases. Treatment management was affected in 57.1% of patients with oligometastases.

Imaging of the post-operative orbit and associated complications.

Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.

Management Impact of 68Ga-DOTATATE PET/CT in Neuroendocrine Tumors.

PURPOSE: The goal of our retrospective single tertiary academic medical center investigation was to examine the added diagnostic value and clinical impact of 68Ga-DOTATATE PET/CT in the therapeutic management of patients with neuroendocrine tumors (NETs). METHODS: Imaging database was queried for all "PET-DOTATATE" examinations performed at our tertiary care academic institution using MONTAGE™. The patient's clinical history and recent prior imaging were reviewed. The additional diagnostic value and clinical management impact of 68Ga-DOTATATE were assessed through retrospective chart review. RESULTS: A total of 81 68Ga-DOTATATE PET/CT scans in 74 patients were found, and 11 patients were excluded from analysis as they had no prior imaging available for comparison, with resultant analysis cohort of 63 patients. Six patients had 2 or more 68Ga-DOTATATE PET/CT examinations. The most common primary diagnosis was undifferentiated NET (63.5%), followed by carcinoid (27.0%), paraganglioma (4.8%), insulinoma (3.2%), and pheochromocytoma (1.6%). The primary sites of disease from the most to the least common were the pancreas (36.5%), small bowel (22.2%), unknown primary (15.9%), lung (6.3%), large bowel (6.3%), and mesentery (4.8%), and other locations accounted for 7.9%. In patients who had prior imaging available for comparison, there were new lesions identified on 68Ga-DOTATATE PET/CT in 21 patients (33.3%) that were not identified on other prior imaging modalities. Of these patients, 5 underwent subsequent MRI and 1 had a repeat 68Ga-DOTATATE PET/CT to further characterize new lesions seen. Moreover, 15 patients (23.8%) had a change in treatment plan, including altering medical therapy in 9 patients, change in planned extent of surgical management in 5 patients, and cancelation of a planned primary tumor resection in 1 patient with metastatic disease. CONCLUSION: Our retrospective cohort demonstrated that 68Ga-DOTATATE PET/CT improves lesion detection over conventional imaging in 33.3% and impacts the therapeutic management in 23.8% of patients with NET.

Posterior Reversible Encephalopathy Syndrome (PRES): Pathophysiology and Neuro-Imaging.

Posterior reversible encephalopathy syndrome (PRES) represents a unique clinical entity with non-specific clinical symptoms and unique neuroradiological findings. This syndrome may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury. In this article, we will review the clinical, typical, and atypical radiological features of PRES, as well as the most common theories behind the pathophysiology of PRES. Additionally, we will discuss some of the treatment strategies for PRES related to the underlying disease state.

Recent advances in the development of nanoparticles for multimodality imaging and therapy of cancer.

This review explores recent work directed toward the development of nanoparticles (NPs) for multimodality cancer imaging and targeted cancer therapy. In the growing era of precision medicine, theranostics, or the combined use of targeted molecular probes in diagnosing and treating diseases is playing a particularly powerful role. There is a growing interest, particularly over the past few decades, in the use of NPs as theranostic tools due to their excellent performance in receptor target specificity and reduction in off-target effects when used as therapeutic agents. This review discusses recent advances, as well as the advantages and challenges of the application of NPs in cancer imaging and therapy.

The 2017 Lush Prize Awards.

This year saw eighteen prizewinning projects from eleven countries, and a new award in recognition of the work of Andrew Tyler.

Iodinated benzimidazole PARP radiotracer for evaluating PARP1/2 expression in vitro and in vivo.

BACKGROUND: PARP inhibitors (PARPi) have the potential to impact cancer therapy in a selective patient population; however, despite current patient selection methods clinical trials have shown mixed response rates. It is therefore clinically useful to determine which patients will respond prior to receiving PARPi therapy. One essential biomarker is to measure the level of PARP enzyme expression in tumors. Small molecule radiotracers have been developed to accurately quantify PARP-1 expression in vitro and in vivo. [125I]KX-02-019 is the first report of a radioiodinated analogue of the benzimidazole class of PARPi. Herein, we studied the pharmacological properties of [125I]KX-02-019 as well as the in vivo biodistribution. METHODS: [125I]KX-02-019 was evaluated in both cancer and non-cancer cell lines. We evaluated the pharmacologic properties of [125I]KX-02-019 in live cells by measuring enzyme association and dissociation kinetics, saturation, and specificity. In addition, competitive inhibition experiments were carried out with commercially available PARPi. Protein expression was analyzed by Western blot to compare PARP-1 and PARP-2 expression across cell lines studied. The biodistribution was studied in a mouse EMT6 tumor model at time points of 0.5, 1, 2, 4 and 6h. RESULTS: [125I]KX-02-019 showed subtle differences in pharmacological properties in the absence of PARP-2. In addition, [125I]KX-02-019 was competitively displaced by clinical PARPi. In vivo biodistribution studies showed an increasing tumor to muscle ratio over 6h as well as fast clearance from healthy tissues. CONCLUSION: [125I]KX-02-019 has binding sites in both PARP1 KO cells as well as PARP2 KO cells showing higher affinity for PARP-2. This observation is supported by a decrease in binding affinity in PARP2 KO cells compared to PARP1 KO cells. The pharmacologic and biological properties of [125I]KX-02-019 studied in vitro and in vivo showed that this analogue may be useful in determining pharmacokinetic and pharmacodynamic properties of clinical PARPi.

A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy.

Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [(125)I] KX1: as a PARP-1-selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo The pharmacologic properties of the PARP radiotracer [(125)I] KX1: was characterized in multiple cell lines where single-agent sensitivity was correlated with [(125)I] KX1: binding to PARP-1. In vivo evaluation of [(125)I] KX1: verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [(125)I] KX1: correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516-24. ©2016 AACR.

The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. METHODS: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. RESULTS: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. CONCLUSION: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC.