Pancreatic fibrosis assessment and association with pancreatic cancer: comparison with the extracellular volume fraction.

AIMS: To compare the iodine washout rate (IWR) from multiphasic contrast-enhanced computed tomography (CT) with the extracellular volume fraction (fECV) for assessing pancreatic fibrosis and its association with pancreatic cancer. MATERIALS AND METHODS: The study included 51 individuals (33 men; median age: 69 years; 21 with pancreatic cancer, 30 with other diseases) who underwent multiphasic contrast-enhanced CT and histological evaluation for fibrotic changes in pancreas. The histological pancreatic fibrosis fraction (HPFF) was assessed on Azan-stained sections. Pancreatic parenchymal enhancement values were measured to calculate IWR and fECV. Statistical methods, such as Spearman's rho and Mann-Whitney U-test, were used. Linear regression models using IWR and fECV were constructed to predict HPFF, with the performance expressed as root mean squared error (RMSE) and Akaike information criterion (AIC). RESULTS: HPFF correlated with all CT parameters at the estimated transection line, strongest for IWRPPP-EP (r=-0.69, P<0.01). HPFF and fECV values were higher in the pancreatic cancer group than in controls (30% vs. 12.5%, P<0.01; 40.3% vs. 33.0%, P<0.01), whereas IWR values were lower (IWRPPP-EP: 43.3% vs. 55.0%, P<0.01; IWRPVP-EP: 25.0% vs. 33.5%, P<0.01). Linear regression models combining IWRPPP-EP + fECV and IWRPVP-EP + fECV were superior for predicting HPFF, with lower RMSE (9.23-9.35) and AIC (379.38-380.72) values than models with IWR or fECV alone. CONCLUSION: IWRPPP-EP, IWRPVP-EP, and fECV were reliable biomarkers for noninvasively assessing pancreatic fibrosis and were associated with pancreatic cancer risk. Linear regression combining these variables showed enhanced predictive accuracy for pancreatic fibrosis.

Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning-based filter using convolutional neural network.

OBJECTIVES: To reveal the utility of motion artifact reduction with convolutional neural network (MARC) in gadoxetate disodium-enhanced multi-arterial phase MRI of the liver. METHODS: This retrospective study included 192 patients (131 men, 68.7 ± 10.3 years) receiving gadoxetate disodium-enhanced liver MRI in 2017. Datasets were submitted to a newly developed filter (MARC), consisting of 7 convolutional layers, and trained on 14,190 cropped images generated from abdominal MR images. Motion artifact for training was simulated by adding periodic k-space domain noise to the images. Original and filtered images of pre-contrast and 6 arterial phases (7 image sets per patient resulting in 1344 sets in total) were evaluated regarding motion artifacts on a 4-point scale. Lesion conspicuity in original and filtered images was ranked by side-by-side comparison. RESULTS: Of the 1344 original image sets, motion artifact score was 2 in 597, 3 in 165, and 4 in 54 sets. MARC significantly improved image quality over all phases showing an average motion artifact score of 1.97 ± 0.72 compared to 2.53 ± 0.71 in original MR images (p < 0.001). MARC improved motion scores from 2 to 1 in 177/596 (29.65%), from 3 to 2 in 119/165 (72.12%), and from 4 to 3 in 34/54 sets (62.96%). Lesion conspicuity was significantly improved (p < 0.001) without removing anatomical details. CONCLUSIONS: Motion artifacts and lesion conspicuity of gadoxetate disodium-enhanced arterial phase liver MRI were significantly improved by the MARC filter, especially in cases with substantial artifacts. This method can be of high clinical value in subjects with failing breath-hold in the scan. KEY POINTS: • This study presents a newly developed deep learning-based filter for artifact reduction using convolutional neural network (motion artifact reduction with convolutional neural network, MARC). • MARC significantly improved MR image quality after gadoxetate disodium administration by reducing motion artifacts, especially in cases with severely degraded images. • Postprocessing with MARC led to better lesion conspicuity without removing anatomical details.

In-vitro fertilisation-embryo-transfer complicates the antenatal diagnosis of placenta accreta spectrum using MRI: a retrospective analysis.

AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.

Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

Hepatobiliary phase hypointense nodule without arterial phase hyperenhancement as a risk factor for late recurrence (>1 year) of hepatocellular carcinoma after surgery.

AIM: To evaluate the value of magnetic resonance imaging (MRI) features, including liver stiffness measured by magnetic resonance elastography (MRE) and the presence of hepatobiliary phase (HBP) hypointense nodule without arterial phase hyperenhancement (APHE), for predicting late recurrence (>1 year) after surgery for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 124 consecutive patients who had undergone surgery for HCC and preoperative MRI. After excluding patients with early recurrence within 1 year after surgery, 89 patients were analysed. Preoperative MRI images were reviewed by a radiologist to record imaging findings, including (1) liver stiffness by MRE, (2) size of the HCCs, (3) number of HCCs, and (4) presence of HBP hypointense nodule without APHE. Pathological findings included tumour grade, vascular/biliary/capsule invasion, and fibrosis stage of the liver. Considering imaging/pathological findings and patients' characteristics as dependent variables, Cox proportional hazards model analysis was performed to identify independent factors associated with late recurrence after surgery. RESULTS: The median follow-up period was 37.3 months. During follow-up, 29 patients (32.5%) developed late recurrence after surgery. In multivariate analysis, underlying liver disease (viral hepatitis) and presence of HBP hypointense nodules without APHE (p=0.010 and 0.033, respectively) were independently associated with disease-free survival (DFS). Kaplan-Meier analysis revealed that patients with HBP hypointense nodules without APHE had a significantly lower DFS rate than those without the nodule (39.2% versus 74.1% at 3 years after surgery, p=0.008). CONCLUSION: The presence of HBP hypointense nodules without APHE was an indicator of late recurrence after surgery for HCC.

Cancer survivors exhibit a different relationship between muscle strength and health-related quality of life/fatigue compared to healthy subjects.

We investigated the difference in relationship between muscle strength and quality of life (QOL)/fatigue in long-term cancer survivors and healthy subjects. Thirty-six cancer survivors and 29 healthy subjects were assessed for body composition and bone status at the calcaneus using the Osteo Sono Assessment Index. Muscle strength was evaluated via handgrip and knee extensor strength. Health-related QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. Fatigue was measured using the brief fatigue inventory. Cancer survivors exhibited lower QOL scores in the physical functioning, physical role function, bodily pain and general health domains (p < .05). Grip and knee extension muscle strength in cancer survivors was positively correlated with the physical function and bodily pain of QOL (p < .05). The usual fatigue subscale score was only significantly higher in cancer survivors than in healthy subjects (p < .05). However, there were no correlations between muscle strength and fatigue in cancer survivors. Our results showed that muscle strength was an important factor for improving QOL in cancer survivors. We believe that the findings of this study will be relevant in the context of planning rehabilitation for cancer survivors.

Anatomical study of the inferior patellar pole and patellar tendon.

In this study, detailed investigations into the shape of the inferior patellar pole, the site of the patellar tendon attachment, and the length and course of the patellar tendon were performed with the aim of examining the anatomical factors involved in the developmental mechanism of patellar tendinitis. The investigation examined 100 legs from 50 cadavers. The inferior patellar pole was classified into three types: pointed, intermediate, and blunt. The attachment of the patellar tendon to the inferior patellar pole was classified into two types: an anterior and a posterior. The length of the patellar tendon was measured from the tibial tuberosity to the inferior patellar pole. The pointed type was seen in 57% of legs, the intermediate type in 21%, and the blunt type in 22%. Twenty-one legs were the pointed type, as well as the anterior type. The patellar tendon was significantly shorter with the posterior type than with the anterior type. The blunt type also had a significantly shorter patellar tendon than the pointed type. In legs that were both the pointed type and the anterior type, the inferior patellar pole and the proximal posterior surface of the patellar tendon impinged during knee flexion due to the posterior tilt of the patella, suggesting the possibility that this may induce damage. With the posterior type and blunt type, on the other hand, the possibility of strong tensile stress on the tendon fibers of the posterior facet of the inferior patellar pole was suggested.

Gender differences of muscle and crural fascia origins in relation to the occurrence of medial tibial stress syndrome.

Although women reportedly have a higher prevalence of medial tibial stress syndrome (MTSS) than men, the possible role of gender-based anatomical differences has not been investigated. The aim of the present study was to investigate the presence of gender-based differences in the range of muscle attachments along the entire medial tibia, the proportion of muscle attachment at the middle and distal thirds of the medial margin of the tibia, the structure of the crural fascia, and chiasm position. The specimens were 100 legs of 55 Japanese cadavers. Statistical analysis was carried out using a chi-square test to compare anatomical features between the sexes. The flexor digitorum longus (FDL) had a higher proportion of attachment to the middle and distal thirds of the medial margin of the tibia than the soleus (SOL; P < 0.001). The proportion of the SOL attachment to the middle and distal thirds of the medial margin of the tibia was 33.3% in men and 72.5% in women (P < 0.001). The soleal aponeurosis was not observed in any specimen. In all specimens the FDL formed the top layer of both chiasms. These results suggest that the higher prevalence of MTSS reported among women may be the result of gender-based anatomical differences.

Site Specificity of Changes in Cortical Oxyhaemoglobin Concentration Induced by Water Immersion.

Our previous studies have shown that water immersion (WI) changes sensorimotor processing and cortical excitability in the sensorimotor regions of the brain. The present study examined the site specificity of the brain activation during WI using functional near infrared spectroscopy (fNIRS). Cortical oxyhaemoglobin (O2Hb) levels in the anterior and posterior parts of the supplementary motor area (pre-SMA and SMA), primary motor cortex (M1), primary somatosensory cortex (S1), and posterior parietal cortex (PPC) were recorded using fNIRS (OMM-3000; Shimadzu Co.) before, during, and after WI in nine healthy participants. The cortical O2Hb levels in SMA, M1, S1, and PPC significantly increased during the WI and increased gradually along with the filling of the WI tank. These changes were not seen in the pre-SMA. The results show that WI-induced increases in cortical O2Hb levels are at least somewhat site specific: there was little brain activation in response to somatosensory input in the pre-SMA, but robust activation in other areas.

Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy.

OBJECTIVES: The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats. METHODS: Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed. RESULTS: Direct ES significantly reduced the disuse-induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups. CONCLUSIONS: These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone.

Effective and selective stretching of the medial head of the gastrocnemius.

Muscle injury frequently occurs in the medial head of the gastrocnemius (MG), and stretching is used for treatment. However, there are no studies based on anatomical considerations and biomechanics. This study therefore examined the macroscopic anatomical structure of the triceps surae muscle to design an effective and selective MG stretching method, before quantitatively verifying that method by ultrasonography. The macroscopic anatomy was analyzed in 16 Japanese cadavers (25 legs). Based on the anatomical findings and the arrangement of fascicles in the MG, we concluded that ankle inversion might be advantageous for selective stretching of the tendon fiber bundles into which the MG inserts. We devised a method in which the limb was initially positioned with the knee joint in extension and the ankle joint in plantar flexion. Then, the ankle was dorsiflexed and inverted. The proposed method was compared with standard stretching and verified by ultrasonography in eight healthy adult males. This method effectively and selectively stretched the MG, producing a significantly decreased pennation angle and increased muscle fiber length. This method may be beneficial for preventing future injuries and may enhance the effect of therapy on the MG.

The twisted structure of the human Achilles tendon.

The Achilles tendon (AT) consists of fascicles that originate from the medial head of the gastrocnemius (MG), lateral head of the gastrocnemius (LG), and soleus muscle (Sol). These fascicles are reported to have a twisted structure. However, there is no consensus as to the degree of torsion. The purpose of this study was to investigate the twisted structure of the AT at the level of fascicles that originate from the MG, LG, and Sol, and elucidate the morphological characteristics. Gross anatomical study of 60 Japanese cadavers (111 legs) was used. The AT fascicles originated from the MG, LG, and Sol were fused while twisting among themselves. There were three classification types depending on the degree of torsion. Further fine separation of each fascicle revealed MG ran fairly parallel in all types, whereas LG and Sol, particularly of the extreme type, were inserted onto the calcaneal tuberosity with strong torsion. In addition, the sites of Sol torsion were 3-5 cm proximal to the calcaneal insertion of the AT. These findings provide promising basic data to elucidate the functional role of the twisted structure and mechanisms for the occurrence of AT injury and other conditions.

Electrical stimulation of denervated rat skeletal muscle retards trabecular bone loss in early stages of disuse musculoskeletal atrophy.

OBJECTIVES: We aimed to determine the intensity of muscle stimulation required to prevent structural failure as well as bone and skeletal muscle loss after denervation-induced disuse. METHODS: Seven-week-old rats (weight, 198-225 g) were randomly assigned to age-matched groups comprising control (CON), sciatic nerve denervation (DN) or direct electrical stimulation (ES) one day later [after denervation] with 4, 8 and 16 mA at 10 Hz for 30 min/day, six days/week, for one or three weeks. Bone architecture and mean osteoid thickness in histologically stained tibial sections and tension in tibialis anterior muscles were assessed at one and three weeks after denervation. RESULTS: Direct ES with 16 mA generated 23-30% maximal contraction force. Denervation significantly decreased trabecular bone volume fraction, thickness and number, connectivity density and increased trabecular separation in the DN group at weeks one and three. Osteoid thickness was significantly greater in the ES16 group at week one than in the DN and other ES groups. Trabecular bone volume significantly correlated with muscle weight. CONCLUSIONS: Relatively low-level muscle contraction induced by low-frequency, high-intensity electrical muscle stimulation delayed trabecular bone loss during the early stages (one week after DN) of musculoskeletal atrophy due to disuse.

Modulation of pain perception through transcranial alternating current stimulation and its nonlinear relationship with the simulated electric field magnitude.

BACKGROUND: Oscillatory activities observed in multiple regions are closely associated with the experience of pain. Specifically, oscillatory activities within the theta- and beta-frequency bands, observed in the left dorsolateral prefrontal cortex (DLPFC), have been implicated in pain perception among healthy individuals and those with chronic pain. However, their physiological significance remains unclear. METHODS: We explored the modulation of pain perception in healthy individuals by theta- and beta-band transcranial alternating current stimulation (tACS) over the left DLPFC and examined the relationship between the modulation effect and magnitude of the electric field elicited by tACS in the left DLPFC using computational simulation. RESULTS: Our findings revealed that both theta- and beta-tACS increased the heat pain threshold during and after stimulation. Notably, the simulated electric field magnitude in the left DLPFC exhibited an inverted U-shaped relationship with the pain modulation effect for theta-tACS. CONCLUSIONS: Our study findings suggested that there would be an optimal electric field strength to produce a high analgesic effect for theta-tACS. SIGNIFICANCE: The application of theta- and beta-tACS interventions targeting the left DLPFC might facilitate the treatment of chronic pain. Furthermore, the attainment of effective pain modulation via theta-tACS over the DLPFC warrants the use of optimal stimulus intensity.

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma.

BACKGROUND: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort. METHODS: In the current retrospective cohort study, we measured serum levels of the eight cytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS). RESULTS: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis. CONCLUSION: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

Changes over time in structural plasticity of trabecular bone in rat tibiae immobilized by reversible sciatic denervation.

OBJECTIVE: The present study aimed to clarify the structural recovery, and to compare the time course of morphological changes in trabeculae and the process of bone mass change in rat tibiae following temporary immobilization of hind limb by sciatic neurectomy or nerve freezing. METHODS: In 11-week-old male Fischer 344 rats, 4-5 mm of the sciatic nerve was removed (neurectomy group) or frozen by 5-second application of a stainless steel rod immersed in liquid nitrogen (nerve-freezing group). Quantitative changes in cancellous bone were assessed by histomorphometry. RESULTS: The results clarified that: trabecular bone volume (BV/TV) decreases until 3 weeks after denervation, and in the nerve-freezing group, it then increases from week 4, recovering to pre-surgery levels by week 10 (no recovery was seen in the neurectomy group); in the initial phase of bone atrophy, the decrease in BV/TV is more gradual in the nerve-freezing group than in the neurectomy group; and changes in trabecular architecture in the bone atrophy-recovery process are strongly associated with changes in trabecular thickness. CONCLUSION: The findings suggested that after transient injury by nerve freezing and subsequent recovery of neuromuscular function, bone tissue undergoes recovery from bone loss, but that trabeculae may not show complete structural recovery.

Extracellular volume fraction using contrast-enhanced CT is useful in differentiating intrahepatic cholangiocellular carcinoma from hepatocellular carcinoma.

Objectives: To evaluate whether tumor extracellular volume fraction (fECV) on contrast-enhanced computed tomography (CT) aids in the differentiation between intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: In this retrospective study, 113 patients with pathologically confirmed ICC (n = 39) or HCC (n = 74) who had undergone preoperative contrast-enhanced CT were enrolled. Enhancement values of the tumor (Etumor) and aorta (Eaorta) were obtained in the precontrast and equilibrium phase CT images. fECV was calculated using the following equation: fECV [%] = Etumor/Eaorta × (100 - hematocrit [%]). fECV values were compared between the ICC and HCC groups using Welch's t-test. The diagnostic performance of fECV for differentiating ICC and HCC was assessed using receiver-operating characteristic (ROC) analysis. fECV and the CT imaging features of tumors were evaluated by two radiologists. Multivariate logistic regression analysis was performed to identify factors predicting a diagnosis of ICC. Results: Mean fECV was significantly higher in ICCs (43.8% ± 13.2%) than that in HCCs (31.6% ± 9.0%, p < 0.001). The area under the curve for differentiating ICC from HCC was 0.763 when the cutoff value of fECV was 41.5%. The multivariate analysis identified fECV (unit OR: 1.10; 95% CI: 1.01-1.21; p < 0.05), peripheral rim enhancement during the arterial phase (OR: 17.0; 95% CI: 1.29-225; p < 0.05), and absence of washout pattern (OR: 235; 95% CI: 14.03-3933; p < 0.001) as independent CT features for differentiating between the two tumor types. Conclusions: A high value of fECV, peripheral rim enhancement during the arterial phase, and absence of washout pattern were independent factors in the differentiation of ICC from HCC.

Lower osteocalcin and osteopontin contents of the femoral head in hip fracture patients than osteoarthritis patients.

UNLABELLED: In patients with femoral neck fracture, clinical factors, bone metabolism markers (in serum, urine, and bone), bone mineral density, radiographic parameters, and bone histomorphometric parameters were investigated to detect determinants of fragility fracture. The osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratio of cortical bone were selected as significant predictors. INTRODUCTION: Measurement of bone mineral density is widely used to assess bone strength, but this also depends on other bone components and on bone structure. The objective of this study was to investigate risk factors for fracture related to bone quality, the patient's history, and the patient's lifestyle. METHODS: Twenty-one patients with femoral neck fracture and 18 patients with osteoarthritis were enrolled. Blood and urine samples were collected on admission to hospital, and bone samples were obtained from femoral necks resected during surgery. Multivariate logistic regression analysis was performed using osteoarthritis and femoral neck fracture as combined variables to assess the influence of alcohol or coffee intake, eating natto (fermented soybeans), osteocalcin and calcium concentrations, the osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratios of cortical bone and cancellous bone, various bone histomorphometric parameters, the bone mineral density of the lumbar spine and the intact contralateral femoral neck, and various radiographic parameters of the spine RESULTS: By forward stepwise multivariate analysis, the osteocalcin/deoxypyridinoline and osteopontin/calcium ratios of cortical bone were selected as significant factors for fracture (the odds ratios were 0.493 and <0.001, respectively; both P<0.001). CONCLUSIONS: A decrease of osteopontin and osteocalcin in bone is important for promoting vulnerability to hip fracture.

Relationship between Shear Stiffness Measured by MR Elastography and Perfusion Metrics Measured by Perfusion CT of Meningiomas.

BACKGROUND AND PURPOSE: When managing meningiomas, intraoperative tumor consistency and histologic subtype are indispensable factors influencing operative strategy. The purposes of this study were the following: 1) to investigate the correlation between stiffness assessed with MR elastography and perfusion metrics from perfusion CT, 2) to evaluate whether MR elastography and perfusion CT could predict intraoperative tumor consistency, and 3) to explore the predictive value of stiffness and perfusion metrics in distinguishing among histologic subtypes of meningioma. MATERIALS AND METHODS: Mean tumor stiffness and relative perfusion metrics (blood flow, blood volume, and MTT) were calculated (relative to normal brain tissue) for 14 patients with meningiomas who underwent MR elastography and perfusion CT before surgery (cohort 1). Intraoperative tumor consistency was graded by a neurosurgeon in 18 patients (cohort 2, comprising the 14 patients from cohort 1 plus 4 additional patients). The correlation between tumor stiffness and perfusion metrics was evaluated in cohort 1, as was the ability of perfusion metrics to predict intraoperative tumor consistency and discriminate histologic subtypes. Cohort 2 was analyzed for the ability of stiffness to determine intraoperative tumor consistency and histologic subtypes. RESULTS: The relative MTT was inversely correlated with stiffness (P = .006). Tumor stiffness was positively correlated with intraoperative tumor consistency (P = .01), while perfusion metrics were not. Relative MTT significantly discriminated transitional meningioma from meningothelial meningioma (P = .04), while stiffness did not significantly differentiate any histologic subtypes. CONCLUSIONS: In meningioma, tumor stiffness may be useful to predict intraoperative tumor consistency, while relative MTT may potentially correlate with tumor stiffness and differentiate transitional meningioma from meningothelial meningioma.

Oestrogen receptor-alpha contributes to the regulation of the hedgehog signalling pathway in ERalpha-positive gastric cancer.

BACKGROUND: Oestrogen receptor-alpha (ERalpha) is highly expressed in diffuse-type gastric cancer and oestrogen increases the proliferation of ERalpha-positive gastric cancer. However, a detailed mechanism by which oestrogen increases the proliferation of these cells is still unclear. METHODS: We used 17-beta-oestradiol (E2) as a stimulator against the ERalpha pathway. Pure anti-oestrogen drug ICI 182 780 (ICI) and small interfering RNA against ERalpha (ERalpha siRNA) were used as inhibitors. Cyclopamine (Cyc) was used as the hedgehog (Hh) pathway inhibitor. Two human ERalpha-positive gastric cancer cells were used as target cells. Effects of the stimulator and inhibitor on E2-induced cell proliferation were also examined. RESULTS: In ERalpha-positive cells, E2 increased not only cell proliferation but also one of the ligands of the Hh pathway, Shh expression. 17-beta-Oestradiol-induced cell proliferation was suppressed by ICI, ERalpha siRNA or Cyc. The increased expression of Shh induced by E2 was suppressed by ICI and ERalpha siRNA but not by Cyc. Furthermore, recombinant Shh activated the Hh pathway and increased cell proliferation, whereas anti-Shh antibody suppressed E2-induced cell proliferation. When a relationship between ERalpha and Shh expressions was analysed using surgically resected gastric cancer specimens, a positive correlation was found, suggesting a linkage between the ERalpha and Hh pathways. CONCLUSION: Our data indicate that activation of the ERalpha pathway promotes cell proliferation by activating the Hh pathway in a ligand-dependent manner through Shh induction of ERalpha-positive gastric cancer.