Gender Differences in a Mouse Model of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular and physiological phenotypes that manifest during the transition to HCC suggest that molecular imaging could provide a non-invasive screening platform to identify the hallmarks of HCC initiation prior to the presentation of clinical disease. We have carried out longitudinal imaging studies on the liver-specific PTEN knockout mouse model using CT, MRI, and multi-tracer PET to interrogate liver size, steatosis, inflammation, and apoptosis. In male PTEN knockout mice, significant steatosis was observed as early as 3 months using both magnetic resonance spectroscopy (MRS) and computed tomography (CT). Enhanced uptake of the apoptosis tracer 18F-TBD was also observed in the livers of male PTEN homozygous knockout mice between 3 and 4 months of age relative to heterozygous knockout controls. Liver uptake of the inflammation tracer [18F]4FN remained relatively low and constant over 7 months in male PTEN homozygous knockout mice, suggesting the suppression of high-energy ROS/RNS with PTEN deletion relative to heterozygous males where the [18F]4FN liver uptake was elevated at early and late time points. All male PTEN homozygous mice developed HCC lesions by month 10. In contrast to the male cohort, only 20% (2 out of 10) of female PTEN homozygous knockout mice developed HCC lesions by month 10. Steatosis was significantly less pronounced in the female PTEN homozygous knockout mice relative to males and could not accurately predict the eventual occurrence of HCC. As with the males, the [18F]4FN uptake in female PTEN homozygous knockout mice was low and constant throughout the time course. The liver uptake of 18F-TBD at 3 and 4.5 months was higher in the two female PTEN knockout mice that would eventually develop HCC and was the most predictive imaging biomarker for HCC in the female cohort. These studies demonstrate the diagnostic and prognostic role of multi-modal imaging in HCC mouse models and provide compelling evidence that disease progression in the PTEN knockout model is highly dependent on gender

Neoadjuvant Relatlimab and Nivolumab in Resectable Melanoma

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen

A Rare Presentation of Lymphoma of the Cervix with Cross-Sectional Imaging Correlation

Non-Hodgkin’s lymphoma of the cervix is an extremely uncommon entity, with no standard established treatment protocol. A 43-year-old asymptomatic female with a history of dual hit blastic B-cell lymphoma/leukemia in complete remission presented with an incidental cervical mass, which was initially felt to represent a cervical fibroid on computed tomography (CT). It was further evaluated with ultrasound, biopsy, and positron emission tomography-computed tomography (PET-CT), which demonstrated a growing biopsy-proven lymphomatous mass and new humeral head lesion. The patient was started on chemotherapy to control the newly diagnosed humeral head lesion, which then regressed. She then underwent radiation to the cervix with significant improvement in the cervical lymphoma. A review of cross-sectional imaging findings of lymphoma of the cervix is provided, including how to differentiate it from other more common diseases of the cervix. Clinical awareness of rare cervical masses such as lymphoma is very important in order to achieve timely diagnosis and appropriate treatment

Massive pulmonary embolism: a comparison of radiological and clinical characteristics and outcomes.

STUDY OBJECTIVES: To describe the clinical features of radiographically massive pulmonary embolism (MPE). DESIGN: Retrospective analysis. SETTING: A 1,368-bed teaching hospital. PATIENTS OR PARTICIPANTS: Patients with pulmonary embolism between June 1997 and December 1999. INTERVENTIONS: Radiographic reports of patients with a radiographic diagnosis of pulmonary embolism were reviewed to determine whether MPE (\u3e50% vascular occlusion) was present. For patients with MPE, vital signs, respiratory and cardiac symptoms, medical history, arterial blood gases, electrocardiographic (ECG) and echocardiographic results, treatment, and hospital mortality were recorded. MEASUREMENTS AND RESULTS: Fifty-four patients with MPE were identified. Patient age range was 28-91 years (mean 71 years). Symptoms were: dyspnea in 38 (70%), chest pain in 21 (38%), syncope in 12 (22%), palpitations in 6 (11%), systolic blood pressure(22%), tachycardia (\u3e120 beats/min) in 15 (28%) and tachypnea (respiratory rate \u3e30) in 15 (28%). Pa O(2) (arterial partial pressure of oxygen) was less than 60 mmHg in 28 (71%) and the alveolar-arterial oxygen gradient was always greater than 20. ECG had an S1Q3T3 pattern in 6 (12%). Echocardiography revealed right ventricular dilatation in 12/31 (38%). Forty-nine patients received anticoagulation treatment, 4 (7%) received thrombolytic therapy with anticoagulation, 5 had inferior vena cava filters (IVC) alone, 6 received IVC filters with anticoagulation, and 2 received thrombolytic therapy, anticoagulation, and IVC filters. Eighteen (33%) patients were treated in the intensive care unit, 3 (5.5%) with mechanical ventilation. Fifty (93%) patients were eventually discharged and 4 (7%) died. Two of the deaths were not attributable to MPE. CONCLUSIONS: Patients with MPE usually present with dyspnea and hypoxemia, and most survive without thrombolytic therapy

Abdominal and pelvic complications of nonoperative oncologic therapy.

Oncologic patients are treated with a combination of chemotherapy, radiation therapy, and surgery. Advances in therapeutic options have greatly improved the survival of patients with cancer. Examples of these advances are newer chemotherapeutic agents that target the cell receptors and advanced radiation therapy delivery systems. It is imperative that radiologists be aware of the variety of imaging findings seen after therapy in patients with cancer. Complications may occur with classic cytotoxic therapies (eg, 5-fluorouracil), usually at higher or prolonged doses or when administered to radiosensitive areas. Newer targeted systemic agents, such as bevacizumab and imatinib, have associated characteristic toxicities because their effects on cells do not depend on dose. Radiation may induce early and late effects in local normal tissues that may be seen at imaging. Imaging findings after chemotherapy include fatty liver, pseudocirrhosis, hepatic veno-occlusive disease, and splenic rupture. Complications of radiation therapy include large and small bowel strictures and radiation-induced hepatitis and tumors. Awareness of the various therapeutic options and knowledge of the spectrum of posttherapeutic complications allows radiologists to provide a comprehensive report that may impact patient management