Automated Quality Evaluation Index for Arterial Spin Labeling Derived Cerebral Blood Flow Maps.

BACKGROUND: Arterial spin labeling (ASL) derived cerebral blood flow (CBF) maps are prone to artifacts and noise that can degrade image quality. PURPOSE: To develop an automated and objective quality evaluation index (QEI) for ASL CBF maps. STUDY TYPE: Retrospective. POPULATION: Data from N = 221 adults, including patients with Alzheimer's disease (AD), Parkinson's disease, and traumatic brain injury. FIELD STRENGTH/SEQUENCE: Pulsed or pseudocontinuous ASL acquired at 3 T using non-background suppressed 2D gradient-echo echoplanar imaging or background suppressed 3D spiral spin-echo readouts. ASSESSMENT: The QEI was developed using N = 101 2D CBF maps rated as unacceptable, poor, average, or excellent by two neuroradiologists and validated by 1) leave-one-out cross validation, 2) assessing if CBF reproducibility in N = 53 cognitively normal adults correlates inversely with QEI, 3) if iterative discarding of low QEI data improves the Cohen's d effect size for CBF differences between preclinical AD (N = 27) and controls (N = 53), 4) comparing the QEI with manual ratings for N = 50 3D CBF maps, and 5) comparing the QEI with another automated quality metric. STATISTICAL TESTS: Inter-rater reliability and manual vs. automated QEI were quantified using Pearson's correlation. P < 0.05 was considered significant. RESULTS: The correlation between QEI and manual ratings (R = 0.83, CI: 0.76-0.88) was similar (P = 0.56) to inter-rater correlation (R = 0.81, CI: 0.73-0.87) for the 2D data. CBF reproducibility correlated negatively (R = -0.74, CI: -0.84 to -0.59) with QEI. The effect size comparing patients and controls improved (R = 0.72, CI: 0.59-0.82) as low QEI data was discarded iteratively. The correlation between QEI and manual ratings (R = 0.86, CI: 0.77-0.92) of 3D ASL was similar (P = 0.09) to inter-rater correlation (R = 0.78, CI: 0.64-0.87). The QEI correlated (R = 0.87, CI: 0.77-0.92) significantly better with manual ratings than did an existing approach (R = 0.54, CI: 0.30-0.72). DATA CONCLUSION: Automated QEI performed similarly to manual ratings and can provide scalable ASL quality control. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Primary sarcoma of the liver: A nationwide analysis of a rare mesenchymal tumor.

BACKGROUND AND OBJECTIVES: Primary liver sarcomas are rare malignancies. Prognostic factors associated with long-term survival remain poorly understood. The objective of this study is to determine factors associated with long-term survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with visceral sarcoma arising from the liver. Demographic factors, tumor characteristics, resection status, and survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival. RESULTS: A total of 743 patients with primary hepatic sarcoma were identified. The median tumor size was 10 cm. Only 30% (n = 221) of patients in the cohort underwent surgery. The 5-year overall survival rates were 47.9% for localized disease, 29.5% for regional disease, and 16.5% for distant disease, p < 0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5-year survival compared with angiosarcoma and other histologic subtypes. On multivariate analysis, surgery was associated with improved survival, while older age, higher stage, and angiosarcoma histology were the strongest independent predictors of poor survival. CONCLUSIONS: Surgery remains the mainstay of treatment for this rare malignancy but is performed in less than one-third of patients. Angiosarcoma histology is associated with worse overall survival, while surgical resection remains the strongest predictor of improved overall survival.

Identifying Indications for Neoadjuvant Therapy in Cholangiocarcinoma.

The recent Hot Topics section focuses on survival rates for patients with cholangiocarcinoma.

Validating biologic age in selecting elderly patients with pancreatic cancer for surgical resection.

BACKGROUND AND OBJECTIVES: Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes. METHODS: The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health-related quality-of-life data. The characteristics of frail and nonfrail patients were compared. RESULTS: Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65-10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47-34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3-79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3-52.4, p = 0.10). In the no-surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85-16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34-7.03, p = 0.02). CONCLUSIONS: The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.

Coronavirus Disease (COVID-19)-Related Disseminated Leukoencephalopathy: A Retrospective Study of Findings on Brain MRI.

Among 2820 inpatients with coronavirus disease (COVID-19), 59 (2.1%) underwent brain MRI. Of them, six (10.2%) had MRI findings suspicious for COVID-19-related disseminated leukoencephalopathy (CRDL), which is characterized by extensive confluent or multifocal white matter lesions (with characteristics and locations atypical for other causes), microhemorrhages, diffusion restriction, and enhancement. CRDL is an uncommon but important differential consideration in patients with neurologic manifestations of COVID-19.

Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.

Skin squamous cell carcinomas (SCCs) are the second most prevalent skin cancers. Chronic skin inflammation has been associated with the development of SCCs, but the contribution of skin inflammation to SCC development remains largely unknown. In this study, we demonstrate that inducible expression of c-fos in the epidermis of adult mice is sufficient to promote inflammation-mediated epidermal hyperplasia, leading to the development of preneoplastic lesions. Interestingly, c-Fos transcriptionally controls mmp10 and s100a7a15 expression in keratinocytes, subsequently leading to CD4 T-cell recruitment to the skin, thereby promoting epidermal hyperplasia that is likely induced by CD4 T-cell-derived IL-22. Combining inducible c-fos expression in the epidermis with a single dose of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) leads to the development of highly invasive SCCs, which are prevented by using the anti-inflammatory drug sulindac. Moreover, human SCCs display a correlation between c-FOS expression and elevated levels of MMP10 and S100A15 proteins as well as CD4 T-cell infiltration. Our studies demonstrate a bidirectional cross-talk between premalignant keratinocytes and infiltrating CD4 T cells in SCC development. Therefore, targeting inflammation along with the newly identified targets, such as MMP10 and S100A15, represents promising therapeutic strategies to treat SCCs.

Evaluation of Indocyanine Green Fluorescence Imaging for Intraoperative Identification of Liver Malignancy.

INTRODUCTION: There is early evidence that indocyanine green (ICG) fluorescence imaging has the ability to detect metastatic and primary malignancies in the liver that are too small to be identified by other methods. However, the rate of false positives and false negatives remains unknown. MATERIALS AND METHODS: This is a single institution prospective single-arm study. Patients with suspected hepatic or pancreatic malignancies were intravenously injected with ICG one to three days prior to their scheduled surgical therapy. At the beginning of the procedure, the liver was assessed with fluorescence imaging and all identified lesions were biopsied and evaluated. RESULTS: Twenty-three patients were enrolled from April 2015 through February 2016. Fifteen patients with confirmed malignancy had adequate fluorescence imaging evaluation of the liver; 10 with pancreatic primary malignancies and five with hepatic primaries. Fluorescence imaging was the only modality that identified nine concerning hepatic lesions, all of which were benign on pathology examination. Out of 11 malignant hepatic masses, six were visible on fluorescence imaging. Out of nine benign hepatic lesions, five were visible. No side effects or complications of the fluorescence imaging were encountered. The sensitivity for ICG fluorescence was 45.5%, the specificity 21.2%, the positive predictive value 25%, and the negative predictive value 40%. CONCLUSION: Intraoperative hepatic assessment with ICG fluorescence imaging to identify malignancy in the liver is feasible and safe. However, in this study the significant number of false positives limit the utility of the technique. Our preliminary data do not support its routine use for detection of malignancies in the liver.

Histopathology-validated machine learning radiographic biomarker for noninvasive discrimination between true progression and pseudo-progression in glioblastoma.

BACKGROUND: Imaging of glioblastoma patients after maximal safe resection and chemoradiation commonly demonstrates new enhancements that raise concerns about tumor progression. However, in 30% to 50% of patients, these enhancements primarily represent the effects of treatment, or pseudo-progression (PsP). We hypothesize that quantitative machine learning analysis of clinically acquired multiparametric magnetic resonance imaging (mpMRI) can identify subvisual imaging characteristics to provide robust, noninvasive imaging signatures that can distinguish true progression (TP) from PsP. METHODS: We evaluated independent discovery (n = 40) and replication (n = 23) cohorts of glioblastoma patients who underwent second resection due to progressive radiographic changes suspicious for recurrence. Deep learning and conventional feature extraction methods were used to extract quantitative characteristics from the mpMRI scans. Multivariate analysis of these features revealed radiophenotypic signatures distinguishing among TP, PsP, and mixed response that compared with similar categories blindly defined by board-certified neuropathologists. Additionally, interinstitutional validation was performed on 20 new patients. RESULTS: Patients who demonstrate TP on neuropathology are significantly different (P < .0001) from those with PsP, showing imaging features reflecting higher angiogenesis, higher cellularity, and lower water concentration. The accuracy of the proposed signature in leave-one-out cross-validation was 87% for predicting PsP (area under the curve [AUC], 0.92) and 84% for predicting TP (AUC, 0.83), whereas in the discovery/replication cohort, the accuracy was 87% for predicting PsP (AUC, 0.84) and 78% for TP (AUC, 0.80). The accuracy in the interinstitutional cohort was 75% (AUC, 0.80). CONCLUSION: Quantitative mpMRI analysis via machine learning reveals distinctive noninvasive signatures of TP versus PsP after treatment of glioblastoma. Integration of the proposed method into clinical studies can be performed using the freely available Cancer Imaging Phenomics Toolkit.

Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers.

Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.

Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma.

EGFRvIII targeted chimeric antigen receptor T (CAR-T) cell therapy has recently been reported for treating glioblastomas (GBMs); however, physiology-based MRI parameters have not been evaluated in this setting. Ten patients underwent multiparametric MRI at baseline, 1, 2 and 3 months after CAR-T therapy. Logistic regression model derived progression probabilities (PP) using imaging parameters were used to assess treatment response. Four lesions from "early surgery" group demonstrated high PP at baseline suggestive of progression, which was confirmed histologically. Out of eight lesions from remaining six patients, three lesions with low PP at baseline remained stable. Two lesions with high PP at baseline were associated with large decreases in PP reflecting treatment response, whereas other two lesions with high PP at baseline continued to demonstrate progression. One patient didn't have baseline data but demonstrated progression on follow-up. Our findings indicate that multiparametric MRI may be helpful in monitoring CAR-T related early therapeutic changes in GBM patients.

Three-dimensional echo planar spectroscopic imaging for differentiation of true progression from pseudoprogression in patients with glioblastoma.

Accurate differentiation of true progression (TP) from pseudoprogression (PsP) in patients with glioblastomas (GBMs) is essential for planning adequate treatment and for estimating clinical outcome measures and future prognosis. The purpose of this study was to investigate the utility of three-dimensional echo planar spectroscopic imaging (3D-EPSI) in distinguishing TP from PsP in GBM patients. For this institutional review board approved and HIPAA compliant retrospective study, 27 patients with GBM demonstrating enhancing lesions within six months of completion of concurrent chemo-radiation therapy were included. Of these, 18 were subsequently classified as TP and 9 as PsP based on histological features or follow-up MRI studies. Parametric maps of choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) were computed and co-registered with post-contrast T1 -weighted and FLAIR images. All lesions were segmented into contrast enhancing (CER), immediate peritumoral (IPR), and distal peritumoral (DPR) regions. For each region, Cho/Cr and Cho/NAA ratios were normalized to corresponding metabolite ratios from contralateral normal parenchyma and compared between TP and PsP groups. Logistic regression analyses were performed to obtain the best model to distinguish TP from PsP. Significantly higher Cho/NAA was observed from CER (2.69 ± 1.00 versus 1.56 ± 0.51, p = 0.003), IPR (2.31 ± 0.92 versus 1.53 ± 0.56, p = 0.030), and DPR (1.80 ± 0.68 versus 1.19 ± 0.28, p = 0.035) regions in TP patients compared with those with PsP. Additionally, significantly elevated Cho/Cr (1.74 ± 0.44 versus 1.34 ± 0.26, p = 0.023) from CER was observed in TP compared with PsP. When these parameters were incorporated in multivariate regression analyses, a discriminatory model with a sensitivity of 94% and a specificity of 87% was observed in distinguishing TP from PsP. These results indicate the utility of 3D-EPSI in differentiating TP from PsP with high sensitivity and specificity.

Differentiation of brain infection from necrotic glioblastoma using combined analysis of diffusion and perfusion MRI.

BACKGROUND: Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently. PURPOSE: To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs. STUDY TYPE: Retrospective. POPULATION: Fourteen patients with brain infections and 21 patients with necrotic GBMs. FIELD STRENGTH/SEQUENCE: 3T MRI, DTI, and DSC-PWI. ASSESSMENT: Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast T1 -weighted and FLAIR images. All lesions were segmented into the central core and enhancing region. For each region, median values of MD, FA, CL, CP, relative CBV (rCBV), and top 90th percentile of rCBV (rCBVmax ) were measured. STATISTICAL TESTS: All parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions. RESULTS: From the central core, significantly lower MD (0.90 × 10-3 ± 0.44 × 10-3 mm2 /s vs. 1.66 × 10-3 ± 0.62 × 10-3 mm2 /s, P = 0.001), significantly higher FA (0.15 ± 0.06 vs. 0.09 ± 0.03, P < 0.001), and CP (0.07 ± 0.03 vs. 0.04 ± 0.02, P = 0.009) were observed in brain infections compared to those in necrotic GBMs. Additionally, from the contrast-enhancing region, significantly lower rCBV (1.91 ± 0.95 vs. 2.76 ± 1.24, P = 0.031) and rCBVmax (3.46 ± 1.41 vs. 5.89 ± 2.06, P = 0.001) were observed from infective lesions compared to necrotic GBMs. FA from the central core and rCBVmax from enhancing region provided the best classification model in distinguishing brain infections from necrotic GBMs, with a sensitivity of 91% and a specificity of 93%. DATA CONCLUSION: Combined analysis of DTI and DSC-PWI may provide better performance in differentiating brain infections from necrotic GBMs. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:184-194.

Neuroimaging Findings in US Government Personnel With Possible Exposure to Directional Phenomena in Havana, Cuba.

IMPORTANCE: United States government personnel experienced potential exposures to uncharacterized directional phenomena while serving in Havana, Cuba, from late 2016 through May 2018. The underlying neuroanatomical findings have not been described. OBJECTIVE: To examine potential differences in brain tissue volume, microstructure, and functional connectivity in government personnel compared with individuals not exposed to directional phenomena. DESIGN, SETTING, AND PARTICIPANTS: Forty government personnel (patients) who were potentially exposed and experienced neurological symptoms underwent evaluation at a US academic medical center from August 21, 2017, to June 8, 2018, including advanced structural and functional magnetic resonance imaging analytics. Findings were compared with imaging findings of 48 demographically similar healthy controls. EXPOSURES: Potential exposure to uncharacterized directional phenomena of unknown etiology, manifesting as pressure, vibration, or sound. MAIN OUTCOMES AND MEASURES: Potential imaging-based differences between patients and controls with regard to (1) white matter and gray matter total and regional brain volumes, (2) cerebellar tissue microstructure metrics (eg, mean diffusivity), and (3) functional connectivity in the visuospatial, auditory, and executive control subnetworks. RESULTS: Imaging studies were completed for 40 patients (mean age, 40.4 years; 23 [57.5%] men; imaging performed a median of 188 [range, 4-403] days after initial exposure) and 48 controls (mean age, 37.6 years; 33 [68.8%] men). Mean whole brain white matter volume was significantly smaller in patients compared with controls (patients: 542.22 cm3; controls: 569.61 cm3; difference, -27.39 [95% CI, -37.93 to -16.84] cm3; P < .001), with no significant difference in the whole brain gray matter volume (patients: 698.55 cm3; controls: 691.83 cm3; difference, 6.72 [95% CI, -4.83 to 18.27] cm3; P = .25). Among patients compared with controls, there were significantly greater ventral diencephalon and cerebellar gray matter volumes and significantly smaller frontal, occipital, and parietal lobe white matter volumes; significantly lower mean diffusivity in the inferior vermis of the cerebellum (patients: 7.71 × 10-4 mm2/s; controls: 8.98 × 10-4 mm2/s; difference, -1.27 × 10-4 [95% CI, -1.93 × 10-4 to -6.17 × 10-5] mm2/s; P < .001); and significantly lower mean functional connectivity in the auditory subnetwork (patients: 0.45; controls: 0.61; difference, -0.16 [95% CI, -0.26 to -0.05]; P = .003) and visuospatial subnetwork (patients: 0.30; controls: 0.40; difference, -0.10 [95% CI, -0.16 to -0.04]; P = .002) but not in the executive control subnetwork (patients: 0.24; controls: 0.25; difference: -0.016 [95% CI, -0.04 to 0.01]; P = .23). CONCLUSIONS AND RELEVANCE: Among US government personnel in Havana, Cuba, with potential exposure to directional phenomena, compared with healthy controls, advanced brain magnetic resonance imaging revealed significant differences in whole brain white matter volume, regional gray and white matter volumes, cerebellar tissue microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks but not in the executive control subnetwork. The clinical importance of these differences is uncertain and may require further study.

Perioperative blood transfusion is associated with an increased risk for post-surgical infection following pancreaticoduodenectomy.

BACKGROUND/PURPOSE: Perioperative blood transfusion is common after pancreaticoduodenectomy (PD) and may predispose patients to infectious complications. The purpose of this study is to examine the association between perioperative blood transfusion and the development of post-surgical infection after PD. METHODS: Patients who underwent PD from 2014 to 2015 were identified in the NSQIP pancreas-specific database. Logistic regression analysis was used to compute adjusted odds ratios (aOR) to identify an independent association between perioperative red blood cell transfusion (within 72 h of surgery) and the development of post-operative infection after 72 h. RESULTS: A total of 6869 patients underwent PD during this time period. Of these, 1372 (20.0%) patients received a perioperative blood transfusion. Patients receiving transfusion had a higher rate of post-operative infection (34.7% vs 26.5%, p < 0.001). After adjusting for significant covariates, perioperative transfusion was independently associated the subsequent development of any post-operative infection (aOR 1.41 [1.23-1.62], p < 0.001), including pneumonia (aOR 2.01 [1.48-2.74], p < 0.001), sepsis (aOR 1.62 [1.29-2.04], p < 0.001), and septic shock (aOR 1.92 [1.38-2.68], p < 0.001). CONCLUSION: There is a strong independent association between perioperative blood transfusion and the development of subsequent post-operative infection following PD.

Neurological Manifestations Among US Government Personnel Reporting Directional Audible and Sensory Phenomena in Havana, Cuba.

Importance: From late 2016 through August 2017, US government personnel serving on diplomatic assignment in Havana, Cuba, reported neurological symptoms associated with exposure to auditory and sensory phenomena. Objective: To describe the neurological manifestations that followed exposure to an unknown energy source associated with auditory and sensory phenomena. Design, Setting, and Participants: Preliminary results from a retrospective case series of US government personnel in Havana, Cuba. Following reported exposure to auditory and sensory phenomena in their homes or hotel rooms, the individuals reported a similar constellation of neurological symptoms resembling brain injury. These individuals were referred to an academic brain injury center for multidisciplinary evaluation and treatment. Exposures: Report of experiencing audible and sensory phenomena emanating from a distinct direction (directional phenomena) associated with an undetermined source, while serving on US government assignments in Havana, Cuba, since 2016. Main Outcomes and Measures: Descriptions of the exposures and symptoms were obtained from medical record review of multidisciplinary clinical interviews and examinations. Additional objective assessments included clinical tests of vestibular (dynamic and static balance, vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of convergence, saccadic, and smooth pursuit eye movements), cognitive (comprehensive neuropsychological battery), and audiometric (pure tone and speech audiometry) functioning. Neuroimaging was also obtained. Results: Of 24 individuals with suspected exposure identified by the US Department of State, 21 completed multidisciplinary evaluation an average of 203 days after exposure. Persistent symptoms (>3 months after exposure) were reported by these individuals including cognitive (n = 17, 81%), balance (n = 15, 71%), visual (n = 18, 86%), and auditory (n = 15, 68%) dysfunction, sleep impairment (n = 18, 86%), and headaches (n = 16, 76%). Objective findings included cognitive (n = 16, 76%), vestibular (n = 17, 81%), and oculomotor (n = 15, 71%) abnormalities. Moderate to severe sensorineural hearing loss was identified in 3 individuals. Pharmacologic intervention was required for persistent sleep dysfunction (n = 15, 71%) and headache (n = 12, 57%). Fourteen individuals (67%) were held from work at the time of multidisciplinary evaluation. Of those, 7 began graduated return to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation. Conclusions and Relevance: In this preliminary report of a retrospective case series, persistent cognitive, vestibular, and oculomotor dysfunction, as well as sleep impairment and headaches, were observed among US government personnel in Havana, Cuba, associated with reports of directional audible and/or sensory phenomena of unclear origin. These individuals appeared to have sustained injury to widespread brain networks without an associated history of head trauma.

Psoriasin has divergent effects on the innate immune responses of murine glial cells.

Antimicrobial peptides are an important part of the innate immune defense in the central nervous system (CNS). The expression of the antimicrobial peptides psoriasin (S100A7) is up-regulated during bacterial meningitis. However, the exact mechanisms induced by psoriasin to modulate glial cell activity are not yet fully understood. Our hypothesis is that psoriasin induced pro- and anti-inflammatory signaling pathways as well as regenerative factors to contribute in total to a balanced immune response. Therefore, we used psoriasin-stimulated glial cells and analyzed the translocation of the pro-inflammatory transcription factor nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) in murine glial cells and the expression of pro- and anti-inflammatory mediators by real time RT-PCR, ELISA technique, and western blotting. Furthermore, the relationship between psoriasin and the antioxidative stress transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) was investigated. Stimulation with psoriasin not only enhanced NFκB translocation and increased the expression of the pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) but also neurotrophin expression. Evidence for functional interactions between psoriasin and Nrf2 were detected in the form of increased antioxidant response element (ARE) activity and induction of Nrf2/ARE-dependent heme oxygenase 1 (HO-1) expression in psoriasin-treated microglia and astrocytes. The results illustrate the ability of psoriasin to induce immunological functions in glia cells where psoriasin exerts divergent effects on the innate immune response.

Analysis of 340 Patients with Solid Pseudopapillary Tumors of the Pancreas: A Closer Look at Patients with Metastatic Disease.

INTRODUCTION: Current literature addressing the treatment of solid pseudopapillary neoplasms (SPNs) of the pancreas is limited, particularly for patients with distant metastases. We aimed to define predictive indicators of survival in a large series of patients and assess the outcome of patients with distant metastases. METHODS: The National Cancer Database was queried for patients diagnosed with SPNs of the pancreas between 1998 and 2011. Single predictor univariate analyses were performed on variables including demographics, tumor characteristics, and surgery outcomes, and multivariate Cox proportional hazards survival analysis was then completed with backward elimination. RESULTS: Overall, 340 patients were identified: 82% were female, median age was 39 years, and 84% had no comorbidities. Patients undergoing any type of surgical resection experienced long-term survival (85% 8-year survival). Patients undergoing surgical resection (n = 296) had superior survival (hazard ratio [HR] 21 for no surgery, p < 0.0001), as did patients treated at academic centers and those with private insurance (HR 3.9, p = 0.009; HR 4.9, p = 0.007). Sex, age, tumor size, presence of lymph node metastases, positive surgical margins, and presence of distant metastases were not significant predictors of survival in multivariate analysis. Of 24 patients with distant metastases, seven were treated surgically and experienced long-term survival similar to that of patients without metastases treated surgically (HR 2, p = 0.48). CONCLUSION: SPNs of the pancreas are rare neoplasms with excellent overall survival; however, in a low number of patients they metastasize. Of the few patients with metastatic disease selected for resection, most experienced long-term survival.

Novel Simulation Device for Targeting Tumors in Laparoscopic Ablation: A Learning Curve Study.

INTRODUCTION: A novel 3-dimensional (3D) guidance system was developed to aid accurate needle placement during ablation. METHODS: Five novices and 5 experienced hepatobiliary surgeons were recruited. Using an agar block with analog tumor, participants targeted under 4 conditions: in-line with the ultrasound plane using ultrasound, in-line using 3D guidance, 45° off-axis using ultrasound, and off-axis using 3D guidance. Time to target the tumor, number of withdrawals, and the National Aeronautics and Space Administration Task Load Index were collected. Initial and final parameters for each of the conditions were compared using a within-subjects paired t test. RESULTS: A significant reduction was seen in the number of required withdrawals in all situations when using the 3D guidance (0.75 vs 3.65 in-line and 0.25 vs 3.6 for off-axis). Mental workload was significantly lower when using 3D guidance compared with ultrasound both for novices (29.85 vs 41.03) and experts (31.98 vs 44.57), P < .001 for both. The only difference in targeting time between first and last attempt was in the novice group during off-axis targeting using 3D guidance (115 vs 32.6 seconds, P = .03). CONCLUSION: Though 3D guidance appeared to decrease time to target, this was not statistically significant likely as a result of lack of power in our trial. Three-dimensional guidance did reduce the number of required withdrawals, potentially decreasing complications, as well as mental workload after proficiency was achieved. Furthermore, novices without experience in ultrasound were able to learn targeting with the 3D guidance system at a faster pace than targeting with ultrasound alone.

Validation of Fistula Risk Score calculator in diverse North American HPB practices.

BACKGROUND: Fistula Risk Score (FRS) is a previously developed tool to assess the risk of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD). METHODS: Prospectively collected databases from 4 university affiliated and non-affiliated HPB centers in United States and Canada were used. The influence of individual baseline characteristics, FRS and FRS group on CR-POPF was assessed in univariate and multivariate analyses. FRS calculator performance was assessed using a C-statistic. RESULTS: 444 patients were identified. Pathology, soft pancreas texture and pancreatic duct size were associated with CR-POPF rates (p < 0.001 for each); EBL was not (p = 0.067). The negligible risk group consisted of 50 (11.3%) patients, low risk of 118 (26.6%), moderate 234 (52.7%) and high risk group of 42 (9.5%) patients. The overall rate of CR-POPF was 20%. Of the patients in the negligible risk group, 2% developed CR-POPF, 13.6% of the low risk, 23.1% moderate and 42.9% in the high risk group (p < 0.001). Overall C-statistic was 0.719. CONCLUSION: FRS is robust and able to stratify the risk of developing CR-POPF following PD in diverse North American academic and non-academic institutions. The FRS should be used in research and to guide clinical management of patients post PD in these institutions.