Adipose Triglyceride Lipase Is a Therapeutic Target in Advanced Prostate Cancer That Promotes Metabolic Plasticity.

Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. A better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate cancer (CRPC). Molecular, genetic, or pharmacologic inhibition of ATGL impaired human and murine prostate cancer growth in vivo and in cell culture or organoids under conditions mimicking the tumor microenvironment. Mass spectrometry imaging demonstrated that ATGL profoundly regulates lipid metabolism in vivo, remodeling membrane composition. ATGL inhibition induced metabolic plasticity, causing a glycolytic shift that could be exploited therapeutically by cotargeting both metabolic pathways. Patient-derived phosphoproteomics identified ATGL serine 404 as a target of CAMKK2-AMPK signaling in CRPC cells. Mutation of serine 404 did not alter the lipolytic activity of ATGL but did decrease CRPC growth, migration, and invasion, indicating that noncanonical ATGL activity also contributes to disease progression. Unbiased immunoprecipitation/mass spectrometry suggested that mutation of serine 404 not only disrupts existing ATGL protein interactions but also leads to new protein-protein interactions. Together, these data nominate ATGL as a therapeutic target for CRPC and provide insights for future drug development and combination therapies. SIGNIFICANCE: ATGL promotes prostate cancer metabolic plasticity and progression through both lipase-dependent and lipase-independent activity, informing strategies to target ATGL and lipid metabolism for cancer treatment.

Recent Imaging Updates and Advances in Gynecologic Malignancies.

Gynecologic malignancies are among the most common cancers in women worldwide and account for significant morbidity and mortality. Management and consequently overall patient survival is reliant upon early detection, accurate staging and early detection of any recurrence. Ultrasound, Computed Tomography (CT), Magnetic resonance imaging (MRI) and Positron Emission Tomography-Computed Tomography (PET-CT) play an essential role in the detection, characterization, staging and restaging of the most common gynecologic malignancies, namely the cervical, endometrial and ovarian malignancies. Recent advances in imaging including functional MRI, hybrid imaging with Positron Emission Tomography (PET/MRI) contribute even more to lesion specification and overall role of imaging in gynecologic malignancies. Radiomics is a neoteric approach which aspires to enhance decision support by extracting quantitative information from radiological imaging.

Engaging nurse practitioners and physician assistants to improve patient care and drive productivity in a radiology consult practice at a comprehensive cancer center.

BACKGROUND: The demand for health care in the United States is increasing because of an aging population and an increase in the number of individuals insured. This has led to requests to revamp the primary care infrastructure fundamentally. LOCAL PROBLEM: The optimal use of nurse practitioners (NPs) and physician assistants (PAs) is still a subject of debate, but recently, it was reported that for many medical conditions, NP and PA-managed care outcomes are consistent with physician-managed care outcomes. METHODS: Radiologists' productivity was measured according to relative value units (RVUs)/shift and professional billing changes. Patient care metrics measured were prescribed protocol to patient appointment lead time and number of same-day prescribed imaging protocol changes. INTERVENTIONS: The focus was on radiologists' productivity and patient care for three months before and three months after integrating NP and PA into our abdominal radiology consult service. RESULTS: We observed significant increases in the mean RVUs/shift (15.2 ± 0.9 vs. 6.2 ± 1.8; p = .02), studies read per shift (10.1 ± 0.5 vs. 4.4 ± 1.5; p = .003), revenue per shift hour ($756.20 ± 55.40 vs. $335.40 ± 32.60; p = .007), and protocol prescription to patient appointment lead time (39.3 ± 6.7 days vs. 16.3 ± 2.9 days; p = .005) and saw significant decreases in the mean prescribed CT (19.3 ± 0.6 vs. 3.3 ± 0.6; p = .001) and MRI (11.7 ± 0.6 vs. 8.30 ± 0.12; p = .011) same day protocol changes in NP and PA integrated workflow. CONCLUSIONS: These findings suggest that NP and PA can be effectively integrated into the abdominal radiology consult service, increasing radiologists' productivity and enhancing clinical care.

PAs and NPs improve patient care and productivity in a radiology consult practice.

OBJECTIVE: To evaluate the effects on efficiency and patient care of the addition of physician assistants (PAs) and NPs to the abdominal radiology consult service. METHODS: We obtained radiologist productivity and patient care metrics for 3 months before and 3 months after the integration of PAs and NPs into our consult service. RESULTS: Integrating PAs and NPs into the workflow led to a significant increase in mean RVUs/shift (15.2 ± 0.9 versus 6.2 ± 1.8; P = .02), number of studies read per shift (10.1 ± 0.5 versus 4.4 ± 1.5; P = .003), revenue per shift hour ($756.20 ± $55.40 versus $335.40 ± $132.60; P = .007), protocol prescription to patient appointment lead time (39.3 ± 6.7 versus 16.3 ± 2.9 days; P = .005), and significant decreases in mean CT (19.3% ± 0.6 versus 3.3% ± 0.6; P = .001) and MRI (11.7% ± 0.6 versus 8.3% ± 0.12; P = .011) same-day protocol changes as patient appointments. CONCLUSIONS: PAs and NPs can be effectively integrated into abdominal radiology consult service, increasing the productivity of radiologists, and enhancing clinical care.

Peutz-Jeghers Syndrome and the Role of Imaging: Pathophysiology, Diagnosis, and Associated Cancers.

The Peutz-Jeghers Syndrome (PJS) is an autosomal dominant neoplastic syndrome defined by hamartomatous polyps through the gastrointestinal tract, development of characteristic mucocutaneous pigmentations, and an elevated lifetime cancer risk. The majority of cases are due to a mutation in the STK11 gene located at 19p13.3. The estimated incidence of PJS ranges from 1:50,000 to 1:200,000. PJS carries an elevated risk of malignancies including gastrointestinal, breast, lung, and genitourinary (GU) neoplasms. Patients with PJS are at a 15- to 18-fold increased malignancy risk relative to the general population. Radiologists have an integral role in the diagnosis of these patients. Various imaging modalities are used to screen for malignancies and complications associated with PJS. Awareness of various PJS imaging patterns, associated malignancies, and their complications is crucial for accurate imaging interpretation and patient management. In this manuscript, we provide a comprehensive overview of PJS, associated malignancies, and surveillance protocols.