A Nationwide Study on the Incidence of Breast Cancer in Korean Women with Osteoporosis Receiving Raloxifene Treatment

PurposeRaloxifene is a selective estrogen receptor modulator (SERM), and raloxifene treatment for osteoporosis is reimbursable under the Korean National Health Insurance. Evidence suggests that SERMs use reduces the risk of breast cancer in Asian population. Herein, we retrospectively investigated the protective effect of raloxifene on breast cancer rates in Korean population.MethodsUsing the Health Insurance Review and Assessment Service database, we selected women with osteoporosis aged 50 years and above. Patients treated for at least 2 years with raloxifene were assigned to the user group, whereas the remaining patients were assigned to the non-user group. The effect on breast cancer risk was assessed using the Cox proportional-hazards model with a time-dependent covariate to adjust for immortal time bias.ResultsA total of 322,870 women who were registered between 2010 and 2011 were included. The user group comprised 0.7% (n = 2,307) of the total population. The mean age was 65.7 ± 8.0 years and 67.2 ± 8.6 years in the user and non-user groups, respectively (p < 0.001). There was no difference in the previous use of estrogen replacement between the 2 groups (p = 0.087). The incidence of breast cancer per 1,000 person-years was 0.49 (n = 8) and 0.68 (n = 1,714) in the user and non-user groups, respectively (hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.32–1.27). HR decreased with increase in the treatment duration, but this change was not statistically significant (HR, 1.00, 95% CI, 0.32–3.11 in 2–3 years; HR, 0.63, 95% CI, 0.20–1.94 in 3–4 years; and HR, 0.41, 95% CI, 0.10–1.65 in 4–5 years).ConclusionLong-term treatment with raloxifene in women with osteoporosis was not significantly associated with a reduction in breast cancer rates. However, further investigation is required for a conclusive proof.     

Dynamic 4D MRI for Characterization of Parathyroid Adenomas: Multiparametric Analysis

BACKGROUND AND PURPOSE:The hypervascular nature of parathyroid adenomas can be explored by proper dynamic imaging to narrow the target lesions for surgical exploration. The purpose of this study was to establish MR perfusion characteristics of parathyroid adenomas to differentiate them from their mimics, such as subjacent thyroid tissue and cervical lymph nodes.MATERIALS AND METHODS:Preoperative high-spatial and -temporal resolution dynamic 4D contrast-enhanced MR imaging in 30 patients with surgically proved parathyroid adenomas was evaluated retrospectively. Using coregistered images, we placed ROIs over the parathyroid adenoma, thyroid gland, and a cervical lymph node (jugulodigastric) to obtain peak enhancement, time-to-peak, wash-in, and washout in each patient. Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic analysis was performed to determine the optimal parameters for determination of parathyroid adenomas versus thyroid tissue and cervical lymph nodes.RESULTS:Parathyroid adenomas showed significantly (P < .05) faster time-to-peak, higher wash-in, and higher washout compared with cervical lymph nodes and significantly (P < .05) higher peak enhancement, faster time-to-peak, higher wash-in, and higher washout compared with thyroid tissue. Logistic regression analysis indicated significant contribution from time-to-peak (P = .02), wash-in (P = .03), and washout (P = .008) for differentiation of parathyroid adenomas from thyroid and cervical lymph nodes. Using receiver operating characteristic analysis, we obtained the best diagnostic accuracy from a combination of time-to-peak/wash-in/washout in the differentiation of parathyroid adenomas versus lymph nodes (area under the curve, 0.96; sensitivity/specificity, 88%/90%) and in distinguishing parathyroid adenomas versus thyroid tissue (area under the curve, 0.96; sensitivity/specificity, 91%/95%).CONCLUSIONS:Dynamic 4D contrast-enhanced MR imaging can be used to exploit the hypervascular nature of parathyroid adenomas. Multiparametric MR perfusion can distinguish parathyroid adenomas from subjacent thyroid tissue or lymph nodes with diagnostic accuracies of 96%.

Single parathyroid adenoma (PTA) is the most common cause of primary hyperparathyroidism, accounting for approximately 80%–90% of all cases.¹ Definitive treatment requires surgical excision, and preoperative localization with imaging is commonly used to decrease the size of surgical incisions and complication rates.²Imaging has been increasingly used for preoperative detection of parathyroid adenomas. While sonography and technetium Tc99m sestamibi scintigraphy have often been used as first-line imaging to localize PTA, these tests are often inconclusive. This situation has led to the development of multiphasic CT (4D CT), which identifies PTAs through their hypervascular perfusion pattern compared with lymph nodes and the thyroid gland. 4D CT has shown superior accuracy compared with scintigraphy,³ though the radiation dose remains as high as 5.56–10.4 mSv.^4–6MR imaging is an attractive alternative to both scintigraphy and 4D CT due to the lack of radiation and has been used for the evaluation of PTAs with some success,^7–9 though not with the same effectiveness as 4D CT. Traditional technical limitations to localizing PTAs with MR imaging have recently been addressed with modern MR imaging technology. These include limited spatial and temporal resolution for multiphase dynamic contrast-enhanced MR imaging over a large FOV required for parathyroid imaging. This limitation can be addressed by the use of fast imaging tools such as time-resolved imaging with stochastic trajectories (TWIST)¹⁰ and improved parallel imaging techniques such as controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA).¹¹ The second limitation is inhomogeneity of fat suppression in the neck required for detection of small parathyroid adenomas. The Dixon fat-suppression technique¹² can dramatically improve this shortcoming.¹³In this study by using a modified dynamic contrast-enhanced sequence with incorporation of a TWIST-CAIPIRINHA combination and the Dixon fat saturation technique, we sought to describe MR perfusion characteristics of PTAs in a cohort of patients with pathology-proved PTA. We hypothesized that MR perfusion biomarkers can differentiate PTA from PTA mimics, such as subjacent thyroid gland and cervical lymph nodes.     

Measurement of Opening and Closing Angles of Aortic Valve Prostheses In Vivo Using Dual-Source Computed Tomography: Comparison with Those of Manufacturers' in 10 Different Types

Objective

The aims of this study were to compare opening and closing angles of normally functioning mechanical aortic valves measured on dual-source computed tomography (CT) with the manufacturers'' values and to compare CT-measured opening angles according to valve function.

Materials and Methods

A total of 140 patients with 10 different types of mechanical aortic valves, who underwent dual-source cardiac CT, were included. Opening and closing angles were measured on CT images. Agreement between angles in normally functioning valves and the manufacturer values was assessed using the interclass coefficient and the Bland-Altman method. CT-measured opening angles were compared between normal functioning valves and suspected dysfunctioning valves.

Results

The CT-measured opening angles of normally functioning valves and manufacturers'' values showed excellent agreement for seven valve types (intraclass coefficient [ICC], 0.977; 95% confidence interval [CI], 0.962-0.987). The mean differences in opening angles between the CT measurements and the manufacturers'' values were 1.2° in seven types of valves, 11.0° in On-X valves, and 15.5° in ATS valves. The manufacturers'' closing angles and those measured by CT showed excellent agreement for all valve types (ICC, 0.953; 95% CI, 0.920-0.972). Among valves with suspected dysfunction, those with limitation of motion (LOM) and an increased pressure gradient (PG) had smaller opening angles than those with LOM only (p < 0.05).

Conclusion

Dual-source cardiac CT accurately measures opening and closing angles in most types of mechanical aortic valves, compared with the manufacturers'' values. Opening angles on CT differ according to the type of valve dysfunction and a decreased opening angle may suggest an elevated PG.     

Mini-Gastric Bypass to Control Morbid Obesity and Diabetes Mellitus: What Radiologists Need to Know

Laparoscopic mini-gastric bypass surgery is a safe and simple surgical intervention for treating morbid obesity and diabetes mellitus and is now being performed more frequently. Radiologists must be critical in their postoperative evaluation of these patients. In this pictorial review, we explain and illustrate the surgical technique, normal postoperative anatomy, and associated complications as seen on imaging examinations, including fluoroscopy and computed tomography.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes

To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.     

Repositioning Potential of PAK4 to Osteoclastic Bone Resorption

Drug repositioning is a rational approach for expanding the use of existing drugs or candidate drugs to treat additional disorders. Here we investigated the possibility of using the anticancer p21‐activated kinase 4 (PAK4)‐targeted inhibitor PF‐3758309 to treat osteoclast‐mediated disorders. PAK4 was highly expressed in bone marrow cells and was phosphorylated during their differentiation into osteoclasts, and osteoclast differentiation was significantly inhibited by the dominant negative form of PAK4 and by PF‐3758309. Specifically, PF‐3758309 significantly inhibited the fusion of preosteoclasts, the podosome formation, and the migration of preosteoclasts. PF‐3758309 also had in vivo antiresorptive activity in a lipopolysaccharide‐induced bone erosion model and in vitro antiosteoclastogenic activity in the differentiation of human bone marrow–derived cells and peripheral blood mononuclear cells into osteoclasts. These data demonstrate the relevance of PAK4 in osteoclast differentiation and the potential of PAK4 inhibitors for treating osteoclast‐related disorders. © 2015 American Society for Bone and Mineral Research © 2015 American Society for Bone and Mineral Research.