Palliative care and imaging utilisation for patients with cancer.

OBJECTIVE: This observational study explores the association between palliative care (PC) involvement and high-cost imaging utilisation for patients with cancer patients during the last 3 months of life. METHODS: Adult patients with cancer who died between 1 January 2012 and 31 May 2015 were identified. Referral to PC, intensity of PC service use, and non-emergent oncological imaging utilisation were determined. Associations between PC utilisation and proportion of patients imaged and mean number of studies per patient (mean imaging intensity (MII)) were assessed for the last 3 months and the last month of life. Similar analyses were performed for randomly matched case-control pairs (n = 197). Finally, the association between intensity of PC involvement and imaging utilisation was assessed. RESULTS: 3784 patients were included, with 3523 (93%) never referred to PC and 261 (7%) seen by PC, largely before the last month of life (61%). Similar proportions of patients with and without PC referral were imaged during the last 3 months, while a greater proportion of patients with PC referral were imaged in the last month of life. PC involvement was not associated with significantly different MII during either time frame. In the matched-pairs analysis, a greater proportion of patients previously referred to PC received imaging in the period between the first PC encounter and death, and in the last month of life. MII remained similar between PC and non-PC groups. Finally, intensity of PC services was similar for imaged and non-imaged patients in the final 3 months and 1 month of life. During these time periods, increased PC intensity was not associated with decreased MII. CONCLUSIONS: PC involvement in end-of-life oncological care was not associated with decreased use of non-emergent, high-cost imaging. The role of advanced imaging in the PC setting requires further investigation.

Gastrointestinal Stromal Tumor Incidentally Detected on 18F-Fluciclovine PET/CT.

ABSTRACT: We present a case of metastatic gastrointestinal stromal tumor incidentally detected on 18F-fluciclovine PET/CT. A 68-year-old man with history of intermediate-risk prostate cancer (Gleason score 4 + 3 = 7; pT2cN0M0) previously treated with retropubic radical prostatectomy, adjuvant whole pelvis radiation, and androgen deprivation therapy (leuprolide) presented with slowly rising serum prostate-specific antigen over 3 years, concerning for recurrent prostate cancer. To identify potential sites of recurrent disease, an 18F-fluciclovine PET/CT was obtained. Multiple tracer-avid mesenteric masses and enlarged lymph nodes were found throughout the abdomen and pelvis, later biopsy-proven to reflect metastatic gastrointestinal stromal tumor.

Incidentally Detected Oropharyngeal Squamous Cell Carcinoma on 18F-Fluciclovine PET/CT.

We present a case of oropharyngeal squamous cell carcinoma (SCC) of the tongue base incidentally detected on F-fluciclovine PET/CT. A 79-year-old man with history of locally advanced prostate cancer (Gleason score 4 + 5 = 9; cT2cN1M0) previously treated with androgen deprivation therapy (luprolide + bicalutamide) presented with a slowly rising serum prostate-specific antigen over 3 years, concerning for recurrent disease. F-fluciclovine PET/CT, obtained to identify potential sites of recurrence, demonstrated prostate bed uptake with possible left seminal vesicle involvement. Additionally, an exophytic, tracer-avid right tongue base mass was incidentally noted and later confirmed to be p16+ SCC on biopsy.

Developing Quality Measures for Diagnostic Radiologists: Part 2.

The ACR convened a cross-specialty, multidisciplinary technical expert panel to identify and define new measures for quality improvement. These measures can be included in the ACR's National Radiology Data Registry and potentially used in the CMS quality reporting programs. The technical expert panel was tasked with developing measures that reflect the most rigorous clinical evidence and address areas most in need of performance improvement. The measures described in these articles represent a new phase in the ACR's efforts to develop meaningful measures for radiologists that promote population health through diagnostic accuracy, clinical effectiveness, and care coordination.

Developing Quality Measures for Diagnostic Radiologists: Part 1.

The ACR convened a cross-specialty, multidisciplinary technical expert panel to identify and define new measures for quality improvement. These measures can be included in the ACR's National Radiology Data Registry and potentially used in the CMS quality reporting programs. The technical expert panel was tasked with developing measures that reflect the most rigorous clinical evidence and address areas most in need of performance improvement. The measures described in these articles represent a new phase in the ACR's efforts to develop meaningful measures for radiologists that promote population health through diagnostic accuracy, clinical effectiveness, and care coordination.

Imaging of Cerebrovascular Disease in Pregnancy and the Puerperium.

OBJECTIVE: The purpose of this article is to review the unique physiologic changes that characterize pregnancy and the puerperium, some that substantially affect the cerebrovascular system. Conditions that can cause neurologic deterioration and share features with preeclampsia-eclampsia include postpartum angiopathy, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, and amniotic fluid embolism. Other conditions not specific to this patient group include cerebral venous thrombosis, cervicocephalic arterial dissection, ischemic stroke, and hemorrhagic stroke, which can pose specific diagnostic and therapeutic challenges. CONCLUSION: Radiologists must be familiar with the imaging findings of cerebrovascular complications and pathologic entities encountered during pregnancy and the puerperium. Ongoing improvements in understanding of molecular changes during pregnancy and the puerperium and advances in diagnostic tests should allow radiologists to continue to make important contributions to the care of this patient population.

MDCT Diagnosis of Perineural Invasion Involving the Celiac Plexus in Intrahepatic Cholangiocarcinoma: Preliminary Observations and Clinical Implications.

OBJECTIVE: The purpose of this study was to test the hypothesis that soft-tissue infiltration along the celiac plexus and delayed enhancement exceeding two-thirds of the tumor area on preoperative MDCT correlate with histologic evidence of perineural invasion in resected intrahepatic cholangiocarcinomas. MATERIALS AND METHODS: Two experienced abdominal radiologists retrospectively reviewed preoperative multiphasic MDCT scans of 20 patients who underwent resection of intrahepatic cholangiocarcinoma, identifying soft-tissue infiltration along the celiac plexus, delayed enhancement exceeding two-thirds of the tumor area, and maximum tumor diameter. Consensus findings were compared with intratumoral perineural invasion in resected intrahepatic cholangiocarcinomas using the Fisher exact test. RESULTS: Six patients had histologic intratumoral perineural invasion, five of whom had soft-tissue infiltration along the celiac plexus on preoperative MDCT, with corresponding 83.3% sensitivity and 92.9% specificity for perineural invasion and significant association between these MDCT and histologic findings (p = 0.002). No patients with histologic perineural invasion had enhancement exceeding two-thirds of the tumor area on MDCT; sensitivity was 0.0% for this finding. Tumor diameter on MDCT was not significantly associated with perineural invasion at histopathology (p = 0.530). CONCLUSION: Soft-tissue infiltration along the celiac plexus on MDCT is an indicator of perineural invasion in patients with intrahepatic cholangiocarcinoma. The data did not confirm an association between delayed enhancement exceeding two-thirds of the tumor area and perineural invasion. Because perineural invasion from intrahepatic cholangiocarcinoma is associated with a very poor prognosis and is generally a contraindication to surgery, the MDCT diagnosis of celiac plexus perineural invasion in patients with intrahepatic cholangiocarcinoma may have important implications for prognosis and treatment planning.

Progression rates and sample size estimates for PPMS based on the CLIMB study population.

BACKGROUND: The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts. OBJECTIVE: The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression. METHODS: We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n = 1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women's Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression. RESULTS: The PP group had a 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4±9.6; RO: 32.7±9.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS (p < 0.001). Median time from onset to EDSS 6.0 was faster in PPMS (p < 0.001). PPMS patients progressed faster to EDSS 3 (p < 0.001) and from EDSS 3 to 6 (p < 0.001). Median time to sustained progression in the PP group was 4.85 years (95% CI 2.83-8.35), significantly faster than the RO group (p < 0.001). CONCLUSIONS: Our modern PPMS cohort is demographically similar to previously studied cohorts. PPMS is associated with faster disability accrual than ROMS. Current real-world observations of time to sustained progression will inform design of new clinical trials for PPMS.

MRI of the knee and shoulder performed before radiography.

PURPOSE: Available data are limited on the level of adherence to established guidelines for appropriate utilization of MR in musculoskeletal imaging. This study estimates the percentage of MRI examinations for knee and shoulder pain or tendonitis performed without prior radiography, which thus may fall outside the ACR Appropriateness Criteria for the Medicare and commercially insured populations. METHODS: The percentage of MRI examinations for knee and shoulder pain or tendonitis performed without prior radiography was estimated among patients in the Medicare 5% carrier claims limited data set and among commercially insured patients in the Truven Marketscan Treatment Pathways database in 2010. RESULTS: Approximately 28% of all knee MRIs, and 35%-37% of all shoulder MRIs were performed without recent prior radiographs. The extrapolated expense of these potentially unwarranted MRIs in the entire fee-for-service Medicare population was between $20 and $35 million. Between 20% and 23% of patients undergoing knee MRI, and 27%-32% undergoing shoulder MRI, did not have radiographic examination at any point before the MRI in the same calendar year. CONCLUSIONS: MRI performed without prior radiography represents a potential gap in care and should be considered as an area for establishment of performance measures.

MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are prevalent causes of late-onset Parkinson's disease. Here, we show that LRRK2 binds to MAPK kinases (MKK) 3, 6, and 7, and that LRRK2 is able to phosphorylate MKK3, 6 and 7. Over-expression of LRRK2 and MKK6 increased the steady state levels of each protein beyond that observed with over-expression of either protein alone. Co-expression increased levels of MKK6 in the membrane more than in the cytoplasm. The increased expression of LRRK2 and MKK6 requires MKK6 activity. The disease-linked LRRK2 mutations, G2019S, R1441C and I2020T, enhance binding of LRRK2 to MKK6. This interaction was further supported by in vivo studies in C. elegans. RNAi knockdown in C. elegans of the endogenous orthologs for MKK6 or p38, sek-1 and pmk-1, abolishes LRRK2-mediated protection against mitochondrial stress. These results were confirmed by deletion of sek-1 in C. elegans. These data demonstrate that MKKs and LRRK2 function in similar biological pathways, and support a role for LRRK2 in modulating the cellular stress response.

LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans.

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease. We generated lines of Caenorhabditis elegans expressing neuronally directed human LRRK2. Expressing human LRRK2 increased nematode survival in response to rotenone or paraquat, which are agents that cause mitochondrial dysfunction. Protection by G2019S, R1441C, or kinase-dead LRRK2 was less than protection by wild-type LRRK2. Knockdown of lrk-1, the endogenous ortholog of LRRK2 in C. elegans, reduced survival associated with mitochondrial dysfunction. C. elegans expressing LRRK2 showed rapid loss of dopaminergic markers (DAT::GFP fluorescence and dopamine levels) beginning in early adulthood. Loss of dopaminergic markers was greater for the G2019S LRRK2 line than for the wild-type line. Rotenone treatment induced a larger loss of dopamine markers in C. elegans expressing G2019S LRRK2 than in C. elegans expressing wild-type LRRK2; however, loss of dopaminergic markers in the G2019S LRRK2 nematode lines was not statistically different from that in the control line. These data suggest that LRRK2 plays an important role in modulating the response to mitochondrial inhibition and raises the possibility that mutations in LRRK2 selectively enhance the vulnerability of dopaminergic neurons to a stressor associated with Parkinson's disease.