Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis.

BACKGROUND AND AIMS: There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. APPROACH AND RESULTS: We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT < 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89-627) and median SGR was 0.3% per day (IQR, 0.1%-0.8%). Over one-third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03-1.30) and alpha-fetoprotein < 20 ng/mL (OR, 1.90; 95% CI, 1.12-3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08-10.80). Median TDT (169 days; IQR 74-408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers). CONCLUSIONS: In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one-fourth exhibiting rapid growth and over one-third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment.

Addition of [18 F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma.

In this work, we characterize the value of positron emission tomography (PET) with computed tomography (CT) in combination with cross-sectional imaging for staging and prognostication of hepatocellular carcinoma (HCC) patients. In this retrospective cohort study, HCC patients underwent PET-CT after initial staging with contrast-enhanced CT or magnetic resonance imaging (MRI). The benefit of PET-CT was measured by the identification of new HCC lesions, and potential harm was quantified by the number of false positives and subsequent diagnostic evaluation. We used multivariate Cox regression analysis to evaluate the association between the highest grade on PET-CT with the risk of extrahepatic metastasis, progression-free, and overall survival. Among 148 patients, PET-CT detected additional extrahepatic metastasis in 11.9% of treatment-naïve and 13.8% of treatment-experienced patients. PET-CT changed the Barcelona Clinic Liver Cancer (BCLC) staging in 5.9% of treatment-naïve and 18.8% of treatment-experienced patients compared with CT/MRI alone, changing HCC management in 9.9% and 21.3% of patients, respectively. Of the patients, 5% (n = 8) experienced severe physical harm requiring additional procedures to evaluate extrahepatic findings. High tumor grade on PET-CT was independently associated with a higher likelihood of extrahepatic metastasis (hazard ratio [HR], 17.1; 95% confidence interval [CI], 3.6-81.5) and worse overall survival (HR, 2.4; 95% CI, 1.4-4.3). Treatment-experienced patients (versus treatment-naïve patients; HR, 9.7; 95% CI, 1.9-49.4) and BCLC stage A (HR, 8.2; 95% CI, 1.5-45.9; P < 0.01) and BCLC stage B (HR, 20.6; 95% CI, 1.5-282.2; P < 0.05) were more likely to have an upstaging with PET-CT compared with BCLC stage C (reference). PET-CT provides prognostic information and improves tumor staging beyond CT/MRI alone, with subsequent changes in management for patients with HCC.

Comparison of 40% trichloroacetic acid and cryotherapy for the treatment of plantar warts: A single-blind, randomized clinical trial.

Plantar warts can cause pain near the toes and the sole of the foot and may result in referral for treatment. This study was aimed at comparing 40% trichloroacetic acid (TCA) and cryotherapy (Cryo) for the treatment of plantar warts. This single-blind, randomized clinical trial was performed on 60 subjects presenting with plantar wart in Sabzevar, Iran in 2018. The first intervention group was treated with 40% TCA in four sessions within 4 weeks. The second intervention group was treated with Cryo using liquid nitrogen in four sessions within 8 weeks. The mean (SD) age of subjects was 20.16 ± 5.96 years and 68.33% (n = 41) were male. Although the resolution rate of warts in the TCA 40% group was greater than the Cryo group, there was no statistical association found between the two groups by adjusting age, sex, and basal time (P = .648). Findings suggest that although 40% TCA was almost as effective as Cryo in the treatment of plantar warts, considering the lower adverse effects of TCA 40% group as compared to the Cryo group, it could be a proper alternative.

Effect of Structured Teaching Programme on Knowledge, Anxiety and Behavioural Response of Patients Undergoing Endoscopy at a Tertiary Care Hospital.

Upper gastrointestinal endoscopy is a common OPD procedure carried out for diagnostic as well as therapeutic purpose. Limited time for interaction between patients and health workers leads to increased anxiety among patients. This study was carried among 50 patients undergoing planned, diagnostic upper GI endoscopy for the first time at a tertiary care hospital. A pre-experimental study was conducted using single group pre-test post-test design. On the day of appointment, their socio-demographic data, baseline knowledge and anxiety levels were assessed using the structured questionnaire and the State and Trait Anxiety Inventory. The patients were then imparted structured teaching programme on the various aspects of upper GI endoscopy using video, flash cards and flip charts and a pamphlet for later reference. On the day of the procedure, their knowledge and anxiety levels were reassessed using the same tool. The patients were provided another session of structured teaching programme using the same AV aids. The behavioural responses of the patients were then observed during the procedure using an observation checklist. Statistical analysis revealed that the knowledge score of the patients increased significantly following the structured teaching (p <0.0001). The mean pre-test anxiety score decreased significantly following the intervention (p<0.0001), only 4 percent had extreme responses like grabbing the endoscope and not maintaining the position.

Clinical evaluation of CAIPIRINHA: comparison against a GRAPPA standard.

PURPOSE: To evaluate image quality when using a CAIPIRINHA sampling pattern in comparison to a standard GRAPPA sampling pattern in patients undergoing a routine three-dimensional (3D) breathheld liver exam. CAIPIRINHA uses an optimized phase encoding sampling strategy to alter aliasing artifacts in 3D acquisitions to improve parallel imaging reconstruction. MATERIALS AND METHODS: Twenty patient volunteers were scanned using a 3D VIBE acquisition with an acceleration factor of four using a CAIPIRINHA and standard GRAPPA sampling pattern. CAIPIRINHA and GRAPPA images were evaluated by three radiologists in a two alternative forced choice test, and the Wilcoxon signed rank test was performed. RESULTS: The CAIPIRINHA sampling pattern was preferred in an average of 68% of the comparisons, and the Wilcoxon signed rank test showed a significant improvement in CAIPIRINHA images (P = 0.014). This analysis indicates that in the given sample set, CAIPIRINHA preference over the GRAPPA standard was statistically significant. CONCLUSION: This work shows that for an acceleration factor of four, a CAIPIRINHA accelerated VIBE acquisition provides significantly improved image quality in comparison to the current GRAPPA standard. This allows a further reduction in imaging time for similar spatial resolutions, which can reduce long breathhold requirements in abdominal imaging, and may be particularly helpful in patients who cannot provide requisite breathholds with current protocols.

Multiple sclerosis normal-appearing white matter: pathology-imaging correlations.

OBJECTIVE: The study was undertaken to determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis brains. METHODS: Brain tissues were obtained through a rapid postmortem protocol that included in situ magnetic resonance imaging (MRI). Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins, and blood vessels. RESULTS: Forty-eight ROIs from 4 secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged major histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area, and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in nonlesional white matter (WM) were correlated with activated microglia, but not with axonal or myelin integrity. INTERPRETATION: The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities.

Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure.

To determine whether clinical parameters alone can differentiate normal versus decreased systolic left ventricular function in patients with heart failure. Detailed clinical data were collected prospectively from 225 consecutive patients who were hospitalized with heart failure. Findings in patients with normal (ejection fraction > or =45%) or decreased (ejection fraction <45%) left ventricular function were compared. Systolic function was normal in 104 patients (46%) and decreased in 121 patients (54%). Patients with normal function were older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50% vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02) hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007), angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs. 32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52% vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P = 0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were associated with ventricular function in multivariable analysis. However, the sensitivity, specificity, and predictive values for all clinical variables were low. Differences in clinical parameters in heart failure patients with decreased versus normal systolic function cannot predict systolic function in these patients, supporting recommendations that heart failure patients should undergo specialized testing to measure ventricular function.