Cost-effectiveness Analysis of Subcutaneous Infliximab for Inflammatory Bowel Diseases in Sequential Biologic Treatment.

BACKGROUND: Inflammatory bowel disease (IBD) guidelines recommend tumor necrosis factor-α inhibitors (TNFis) for patients who have not responded to conventional therapy, and vedolizumab in case of inadequate response to conventional therapy and/or TNFis. Recent studies have shown that vedolizumab may also be effective in the earlier treatment lines. Therefore, we conducted cost-effectiveness analyses to determine the optimal treatment sequence in patients with IBD. METHODS: A Markov model with a 10-year time horizon compared the cost-effectiveness of different biologic treatment sequences in patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from the UK and French perspectives. Subcutaneous formulations of infliximab, vedolizumab, and adalimumab were evaluated. Comparative effectiveness was based on a network meta-analysis of clinical trials and real-world evidence. Costs included pharmacotherapy, surgery, adverse events, and disease management. RESULTS: The results indicated that treatment sequences starting with infliximab were less costly and more effective than those starting with vedolizumab for patients with UC in the United Kingdom and France, and patients with just CD in France. For patients with CD in the United Kingdom, treatment sequences starting with infliximab resulted in better health outcomes with incremental cost-effectiveness ratios (ICERs) near the threshold. CONCLUSIONS: Based on the ICERs, treatment sequences starting with infliximab are the dominant option for patients with UC in the United Kingdom, and patients with UC and CD in France. In UK patients with CD, ICERs were near the assumed "willingness to pay" threshold. These results reinforce the UK's National Institute for Health and Care Excellence recommendations for using infliximab prior to using vedolizumab in biologics-naïve patients.

A Markov model compared the cost-effectiveness of biologic treatment sequences in patients with moderate to severe inflammatory bowel diseases from a European perspective. The results indicated that treatment sequences starting with infliximab are the dominant option than those starting with vedolizumab.

Updated National Diagnostic Reference Levels and Achievable Doses for CT Protocols: A National Survey of Korean Hospitals.

Background: In 2021, the Korean government proposed a new CT diagnostic reference level. This study performed a nationwide survey and developed new DRLs and AD for 13 common CT examinations. We compared other countries' DRLs for CT examinations. Methods: This study investigated the CTDIvol and DLP of the 12 types of CT protocols for adults and brain CT protocol for pediatrics. A total of 7829 CT examinations were performed using 225 scanners. We defined the DRLs values in the distribution of radiation exposure levels to determine the nationwide patient dose and distribution status of the dose. Results: This study showed that the new Korean national CT DRLs are slightly higher or similar to those of previous surveys and are similar or lower than those of other countries. In some protocols, although the DLP value increased, the CTDIvol decreased; therefore, it can be concluded that the patient's dose in CT examinations was well managed. Conclusions: The new CT DRLs were slightly higher than or similar to that of the previous survey and were evaluated to be similar or lower than CT DRLs of other countries. These DRLs will be used for radiation optimization and effective dose calculation for an individual.

Development of CT Effective Dose Conversion Factors from Clinical CT Examinations in the Republic of Korea.

The aim of this study was to determine the conversion factors for the effective dose (ED) per dose length product (DLP) for various computed tomography (CT) protocols based on the 2007 recommendations of the International Commission on Radiological Protection (ICRP). CT dose data from 369 CT scanners and 13,625 patients were collected through a nationwide survey. Data from 3793 patients with a difference in height within 5% of computational human phantoms were selected to calculate ED and DLP. The anatomical CT scan ranges for 11 scan protocols (adult-10, pediatric-1) were determined by experts, and scan lengths were obtained by matching scan ranges to computational phantoms. ED and DLP were calculated using the NCICT program. For each CT protocol, ED/DLP conversion factors were calculated from ED and DLP. Estimated ED conversion factors were 0.00172, 0.00751, 0.00858, 0.01843, 0.01103, 0.02532, 0.01794, 0.02811, 0.02815, 0.02175, 0.00626, 0.00458, 0.00308, and 0.00233 mSv∙mGy-1∙cm-1 for the adult brain, intra-cranial angiography, C-spine, L-spine, neck, chest, abdomen and pelvis, coronary angiography, calcium scoring, aortography, and CT examinations of pediatric brain of <2 years, 4-6 years, 9-11 years, and 13-15 years, respectively. We determined ED conversion factors for 11 CT protocols using CT data obtained from a nationwide survey in Korea and Monte Carlo-based dose calculations.

NATIONAL DIAGNOSTIC REFERENCE LEVELS AND ACHIEVABLE DOSES FOR 13 ADULT CT PROTOCOLS AND A PAEDIATRIC HEAD CT PROTOCOL: NATIONAL SURVEY OF KOREAN HOSPITALS.

To develop a second set of diagnostic reference levels (DRLs) and achievable doses (ADs) for 13 adult computed tomography (CT) protocols and a paediatric head CT protocol in Korea. A survey of 13,625 CT examinations was performed based on 13 adult CT protocols and a paediatric non-contrast brain CT protocol using 369 CT systems, with patients grouped according to age. Most CT protocols in this survey had DRLs similar to those reported in other countries. However, chest and abdomen-pelvic CT had lower DRLs than those reported in the first Korean national survey and those from other countries. Paediatric non-contrast brain CT in each age group, with the exception of the 11-15-year age group, had lower DRLs than those reported in other countries. The DRLs presented here are similar to (or lower than for some protocols) those reported in the first Korean national survey and those from other countries.

Scientific rationale for extrapolation of biosimilar data across cancer indications: case study of CT-P10.

For a biosimilar to gain regulatory approval, a comprehensive comparability exercise must demonstrate that it is highly similar to its originator biologic, or reference product. Once biosimilarity has been shown, it is possible to approve the biosimilar for additional indications held by the reference product, without clinical trials in these indications. Extrapolation of clinical data is permitted by regulatory agencies as long as it is scientifically justified. CT-P10, a biosimilar of rituximab, was recently approved in Europe for all indications held by its reference product, incorporating both autoimmune diseases and hematological cancers. Here, we review the scientific rationale for extrapolation in biosimilar development using the example of CT-P10 as a case study.

An introduction to biosimilar cancer therapeutics: definitions, rationale for development and regulatory requirements.

Monoclonal antibodies and other biologic drugs play important roles in the treatment of various hematological malignancies and solid tumors. However, such drugs are intrinsically more expensive to develop than small molecules and their clinical benefits are often accompanied by challenges relating to affordability and access. Patent expiry for 'originator' biologics is providing opportunities for a new generation of biosimilar drugs, potentially capable of relieving pressure on healthcare budgets. This article discusses key characteristics of biosimilars, distinguishes them from generics and noncomparable biologics and outlines the robust regulatory requirements that must be followed to establish biosimilarity with a reference product. The path to approval is discussed with reference to the rituximab biosimilar CT-P10, the first licensed monoclonal antibody biosimilar cancer therapeutic.

Scaled Signal Intensity of Uterine Fibroids on T2-Weighted MR Imaging as a Predictor of the Potential Response to Uterine Fibroid Embolization.

PURPOSE: To determine feasibility of scaled signal intensity (SSI) of uterine fibroids on T2-weighted magnetic resonance (MR) images to predict volume reduction rate (VRR) after uterine fibroid embolization (UFE). MATERIALS AND METHODS: In this retrospective study, 66 premenopausal women underwent UFE. Patients underwent follow-up MR imaging 3 months after UFE. SSI of predominant fibroids was measured on T2-weighted MR images obtained before the procedure by standardizing the mean signal intensity to a 0-to-100 scale, with 0 representing rectus abdominis muscle and 100 representing subcutaneous fat (100) for reference values. RESULTS: VRR of predominant fibroids was 12.3%-99.0% (mean 53.7%). SSI of predominant fibroids was 0.9-73.6 (mean 24.6). SSI was significantly related to VRR of fibroids (P < .01). The optimal SSI cutoff value to predict VRR > 50% was 18.16 with sensitivity of 78.8% and specificity of 66.7%. The optimal SSI cutoff value to predict VRR < 30% was 14.38 with sensitivity of 75% and specificity of 70.7%. CONCLUSIONS: SSI of fibroids was significantly related to fibroid VRR after UFE. SSI may be useful in the quantified prediction of volume reduction.

Efficacy of single-dose gonadotropin-releasing hormone agonist administration prior to magnetic resonance-guided focused ultrasound surgery for symptomatic uterine fibroids.

PURPOSE: To investigate the effects of a single-dose GnRHa on the thermal ablation of MRgFUS in women with symptomatic fibroids. MATERIALS AND METHOD: In this pilot study, a single-dose GnRHa was administered in 17 patients with a total of 20 fibroids. Volume and scaled signal intensity (SSI) as an objective marker of fluid contents were prospectively followed up with serial MR scans. The control group of 17 patients with 19 fibroids were retrospectively enrolled and compared with GnRHa group in terms of non-perfused volume (NPV) and thermal dosimetry to assess the efficiency of thermal ablation. RESULTS: About 29 days after GnRHa administration, SSI and volume of fibroids were reduced by 55.1 and 10.6%, respectively (p < 0.05) but no adverse events were reported. NPV per unit energy (0.046 cm3/J ± 0.026 vs. 0.031 cm3/J ± 0.018, p = 0.041) was larger and SSI (8.4 ± 8.0 vs. 13.9 ± 12.0, p = 0.053) was lower in GnRHa group. Linear regression analysis showed that these two parameters were in a reverse correlation (p = 0.011). CONCLUSION: GnRHa is supposed to reduce the fluid contents of fibroids including blood vessels and enhance the tissue responsiveness to thermal energy. A single dose prior to MRgFUS has the potential to improve treatment efficiency, while avoiding the side effects of multiple doses of GnRHa.

New organ-based tube current modulation method to reduce the radiation dose during computed tomography of the head: evaluation of image quality and radiation dose to the eyes in the phantom study.

A new organ-based tube current modulation (NOB-TCM) method was designed with the intent to decrease tube current by 30% over a prescribed 90° radial arc across the anterior aspect of the radiosensitive organ, without increasing tube current in the remaining radial arc. We compared a reference scan and five other dose-reducing methods with regard to effects on dose, practicality, and image quality to determine the most effective method for the reduction of the radiation dose to the eyes during CT examinations of the head. We compared the radiation doses to the eyes and physical image quality in different regions of interest for TCM and shielding scans. Three types of TCM scans were performed: longitudinal TCM, angular TCM, and NOB-TCM. A bismuth sheet and lead goggles were each applied for the shielding scan. Relative to the reference scan, the dose to the eye was reduced to 25.88% with NOB-TCM, 44.53% with lead goggles, and 36.91% with a bismuth shield. Relative to the reference scan, the mean signal-to-noise ratio (SNR) was decreased to 8.02% with NOB-TCM, 28.36% with lead goggles, and 32.95% with the bismuth shield. The SNR of the anterior region of interest was decreased to 11.89% with NOB-TCM and 87.89% with the bismuth shield. The average figure of merit was increased by 11.7% with longitudinal TCM and 13.39% with NOB-TCM, compared with the reference scan. NOB-TCM is a superior solution for head CT, including the orbital area, due to the reduction in radiation exposure without significant loss in image quality.

Anti-Metastatic Effect of Dehydrocorydaline on H1299 Non-Small Cell Lung Carcinoma Cells via Inhibition of Matrix Metalloproteinases and B Cell Lymphoma 2.

Though Dehydrocorydaline, an alkaloid isolated from Corydalis turtschaninovii tuber, was known to have anti-coronary artery disease, anti-inflammatory, apoptotic, anti-allergic, anti-acetylcholinesterase, and antitumor effects, the underlying anti-metastatic mechanism of Dehydrocorydalin was never elucidated in lung cancer cells so far. Thus, in the present study, the anti-metastatic effect of Dehydrocorydaline was examined in non-small cell lung carcinoma (NSCLC) cells, mainly targeting matrix metalloproteinases (MMPs) and B cell lymphoma-2 (Bcl-2) signaling. Here, Dehydrocorydaline exerted weak cytotoxicity and attenuated the protein expression of Bcl-2 and activated Bax in a concentration-dependent manner in NSCLC cells, such as A549, H460, H1299, and H596 cells. Also, Dehydrocorydaline suppressed the migration of H1299 cells by wound healing assay and transwell migration assay. Consistently, Dehydrocorydaline attenuated mRNA and protein levels of MMP7 and MMP9 as metastasis biomarkers in H1299 cells by quantitative reverse transcription polymerase chain reaction. Of note, Bcl-2 overexpression reduced the cytotoxic and anti-metastatic effects of Dehydrocorydaline on pCDNA-Bcl-2 transfected H1299 cells. Overall, our findings provide scientific evidence that Dehydrocorydaline exerts anti-metastatic potential via suppression of MMPs and Bcl-2 signaling in NSCLC cells. Copyright © 2017 John Wiley & Sons, Ltd.

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure.

Rec8 is a prominent component of the meiotic prophase chromosome axis that mediates sister chromatid cohesion, homologous recombination and chromosome synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show here that such cleavage plays no detectable role for chromosomal events of prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24 or 29 alanine substitutions. A distinct 'separation of function' phenotype is revealed. In the mutants, axis formation and recombination initiation are normal, as is non-crossover recombination; in contrast, crossover (CO)-related events are defective. Moreover, the severities of these defects increase coordinately with the number of substitution mutations, consistent with the possibility that global phosphorylation of Rec8 is important for these effects. (iii) We have analyzed the roles of three kinases that phosphorylate Rec8 during prophase. Timed inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8 phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not. Our results suggest that Rec8's prophase function, independently of cohesin cleavage, contributes to CO-specific events in conjunction with the maintenance of homolog bias at the leptotene/zygotene transition of meiotic prophase.

Evaluation of the Patient Effective Dose in Whole Spine Scanography Based on the Automatic Image Pasting Method for Digital Radiography.

BACKGROUND: Whole spine scanography (WSS) is a radiologic examination that requires whole body X-ray exposure. Consequently, the amount of patient radiation exposure is higher than the radiation dose following routine X-ray examination. OBJECTIVES: Several studies have evaluated the patient effective dose (ED) following single exposure film-screen WSS. The objective of this study was to evaluate patient ED during WSS, based on the automatic image pasting method for multiple exposure digital radiography (APMDR). Further, the calculated EDs were compared with the results of previous studies involving single exposure film-screen WSS. PATIENTS AND METHODS: We evaluated the ED of 50 consecutive patients (M:F = 28:22) who underwent WSS using APMDR. The anterior-posterior (AP) and lateral (LAT) projection EDs were evaluated based on the Monte Carlo simulation. RESULTS: Using APMDR, the mean number of exposures was 6.1 for AP and 6.5 for LAT projections. LAT projections required more exposures (6.55%) than AP projections. The mean ED was 0.6276 mSv (AP) and 0.6716 mSv (LAT). The mean ED for LAT projections was 0.6061 mSv in automatic exposure control (AEC) and 0.7694 mSv in manual mode. The relationship between dose-area-product (DAP) and ED revealed a proportional correlation (AP, R(2) = 0.943; LAT, R(2) = 0.773). Compared to prior research involving single exposure screen-film WSS, the patient ED following WSS using APMDR was lower on AP than on LAT projections. CONCLUSION: Despite multiple exposures, ED control is more effective if WSS is performed using APMDR in the AEC mode.

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell.

Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/ß), ß-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, ß-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.

CCR4-NOT2 Promotes the Differentiation and Lipogenesis of 3T3-L1 Adipocytes via Upregulation of PPARx03B3;, CEBPα and Inhibition of P-GSK3α/ß and ß-Catenin.

BACKGROUND/AIMS: Though CCR4-NOT2 (CNOT2), one of CCR4-NOT complex subunits, was known to be involved in metastasis and apoptosis through transcription and mRNA degradation, its other biological function is poorly understood so far. The aim of this study is to elucidate the molecular role of CNOT2 in the differentiation process of 3T3-L1 preadipocytes. METHODS AND RESULTS: CNOT2 was overexpressed during the differentiation process of 3T3-L1 preadipocytes. Consistently, mRNA levels of CNOT2, adiponectin, adiponectin 2, PPARx03B3; and CEBPα were enhanced in 3T3-L1 adipocytes. Conversely, CNOT2 depletion by siRNA transfection also reversed the activation of PPARx03B3; and CEBPα and inhibition of GSK3α/ß and ß-catenin at the protein level in 3T3-L1 preadipocytes. Immunofluorescence assay revealed that CNOT2 was colocalized with PPARx03B3;, but not with CEBPα in 3T3-L1 adipocyte. Consistently, IP western blots revealed that CNOT2 interacted with PPARx03B3; in 3T3-L1 adipocyte. CONCLUSION: Our findings demonstrate that CNOT2 promotes the differentiation of 3T3-L1 preadipocytes via upregulation of PPARx03B3;, and CEBPα and inhibition of GSK3α/ß and ß-catenin signaling as a potent molecular target for obesity.

Scaled signal intensity of uterine fibroids based on T2-weighted MR images: a potential objective method to determine the suitability for magnetic resonance-guided focused ultrasound surgery of uterine fibroids.

OBJECTIVES: Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive method to treat uterine fibroids. To help determine the patient suitability for MRgFUS, we propose a new objective measure: the scaled signal intensity (SSI) of uterine fibroids in T2 weighted MR images (T2WI). METHODS: Forty three uterine fibroids in 40 premenopausal women were included in this retrospective study. SSI of each fibroid was measured from the screening T2WI by standardizing its mean signal intensity to a 0-100 scale, using reference intensities of rectus abdominis muscle (0) and subcutaneous fat (100). Correlation between the SSI and the non-perfused volume (NPV) ratio (a measure for treatment success) was calculated. RESULTS: Pre-treatment SSI showed a significant inverse-correlation with post treatment NPV ratio (p < 0.05). When dichotomizing NPV ratio at 45 %, the optimal cut off value of the SSI was found to be 16.0. CONCLUSIONS: A fibroid with SSI value 16.0 or less can be expected to have optimal responses. The SSI of uterine fibroids in T2WI can be suggested as an objective parameter to help in patient selection for MRgFUS. KEY POINTS: • Signal intensity of fibroid in MR images predicts treatment response to MRgFUS. • Signal intensity is standardized into scaled form using adjacent tissues as references. • Fibroids with SSI less than 16.0 are expected to have optimal responses.

Mitotic cohesin subunit Mcd1 regulates the progression of meiotic recombination in budding yeast.

The cohesin complex holds sister chromatids together and prevents premature chromosome segregation until the onset of anaphase. Mcd1 (also known as Scc1), the α-kleisin subunit of cohesin, is a key regulatory subunit of the mitotic cohesin complex and is required for maintaining sister chromatid cohesion, chromosome organization, and DNA repair. We investigated the function of Mcd1 in meiosis by ectopically expressing Mcd1 during early meiotic prophase I in Saccharomyces cerevisiae. Mcd1 partially regulated the progression of meiotic recombination, sister chromatid separation, and nuclear division. DNA physical analysis during meiotic recombination showed that Mcd1 induced double-strand breaks (DSBs) but negatively regulated homologous recombination during DSB repair; Mcd1 expression delayed post-DSB stages, leading to inefficiencies in the DSB-to-joint molecule (JM) transition and subsequent crossover formation. These findings indicate that meiotic cells undergo Mcd1-mediated DSB formation during prophase I, and that residual Mcd1 could regulate the progression of JM formation during meiotic recombination.

Rad51 regulates cell cycle progression by preserving G2/M transition in mouse embryonic stem cells.

Homologous recombination (HR) maintains genomic integrity against DNA replication stress and deleterious lesions, such as double-strand breaks (DSBs). Rad51 recombinase is critical for HR events that mediate the exchange of genetic information between parental chromosomes in eukaryotes. Additionally, Rad51 and HR accessory factors may facilitate replication fork progression by preventing replication fork collapse and repair DSBs that spontaneously arise during the normal cell cycle. In this study, we demonstrated a novel role for Rad51 during the cell cycle in mouse embryonic stem cells (mESCs). In mESCs, Rad51 was constitutively expressed throughout the cell cycle, and the formation of Rad51 foci increased as the cells entered S phase. Suppression of Rad51 expression caused cells to accumulate at G2/M phase and activated the DNA damage checkpoint, but it did not affect the self-renewal or differentiation capacity of mESCs. Even though Rad51 suppression significantly inhibited the proliferation rate of mESCs, Rad51 suppression did not affect the replication fork progression and speed, indicating that Rad51 repaired DNA damage and promoted DNA replication in S phase through an independent mechanism. In conclusion, Rad51 may contribute to G2/M transition in mESCs, while preserving genomic integrity in global organization of DNA replication fork.

Feasibility of MDCT angiography for determination of tumor-feeding vessels in chemoembolization of hepatocellular carcinoma.

OBJECTIVE: To investigate the feasibility and accuracy of multidetector computed tomography (MDCT) angiography for assessment of subsegmental tumor-feeding vessels in transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 23 patients with 36 HCCs who underwent TACE during a 14-month period were enrolled. All patients underwent 3-phase dynamic MDCT within a month before TACE. Arterial phase MDCT images were retrospectively reformatted and analyzed for determination of single subsegmental tumor-feeding vessel using maximum intensity projection (MIP) and volume-rendering technique (VRT). Two radiologists independently assessed and scored the MIP and VRT images using 4-grade visual scores (grade 1, no depiction of tumor-feeding vessel; grade 2, indeterminate tumor-feeding vessel; grade 3, probable tumor-feeding vessel; and grade 4, good depiction of tumor-feeding vessel). The weighted kappa test was used to determine interobserver variability, and Wilcoxon signed rank test was used to differentiate visual scores of each technique. Results of digital subtraction angiography were defined as the criterion standard; therefore, assessment of subsegmental tumor-feeding vessel using MIP or VRT was compared with digital subtraction angiography, and the accuracy of each technique was calculated. RESULTS: Interobserver agreement (weighted kappa, 0.746 on VRT and 0.806 on MIP) was substantial to almost perfect. The visual scores for MIP (mean, 3.64 for reviewer 1 and 3.5 for reviewer 2) were higher than those for VRT (mean, 2.11 for reviewer 1 and 2.22 for reviewer 2; P = 0.000). The accuracy for assessing subsegmental tumor-feeding vessel was 22.2% for VRT and 77.8% for MIP. CONCLUSION: Multidetector CT angiography using MIP showed good imaging quality and high accuracy for determination of subsegmental tumor-feeding vessels.

Magnetic resonance imaging-guided focused ultrasound surgery for symptomatic uterine fibroids: estimation of treatment efficacy using thermal dose calculations.

OBJECTIVE: To study the correlation between the predicted thermal dose volume (TDV) and the actual ablation volumes in MR-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine fibroids, and to follow up the outcome for 12 months post-treatment. STUDY DESIGN: Phase-difference fast spoiled gradient-echo MR images were used to analyze thermal change during the energy deliveries of MRgFUS in 60 consecutive patients treated for symptomatic uterine fibroids. The TDV obtained through analysis of these MR images was compared with the non-perfused volume (NPV) measured on post-treatment contrast enhanced T1-weighted images. Final values of TDV ratio and NPV ratio were obtained by dividing these values by original fibroid volume. Patients were followed for 12 months post-treatment to assess symptomatic relief using the symptom severity score (SSS). RESULTS: Treatments in which we managed to reach a TDV ratio larger than 27% of the treated fibroid yielded a ratio of NPV to TDV of 1.1±0.5, indicating accurate control of the non-invasive procedure. Patient symptoms, as measured by the SSS, continuously decreased from a mean baseline score of 50±22 to 19±12 (P<0.0001) 12 months post-treatment. CONCLUSIONS: At large treatment volumes (exceeding 27% TDV ratio), thermal dose estimates correspond very closely to non-perfused volumes measured immediately post treatment. These large treatment volumes result in continuous clinical improvement throughout the first 12 months after MRgFUS.

Magnetic resonance imaging-guided focused ultrasound treatment of pedunculated subserosal uterine fibroids: a preliminary report.

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided focused ultrasound (US) as a treatment for pedunculated subserosal fibroids. MATERIALS AND METHODS: Over a 2-year period (March 2007 to March 2009), 135 women with symptomatic uterine fibroids were treated in the authors' institution using MR imaging-guided focused US. Of these women, nine (mean age, 39 years; range, 25-47 y) had a single pedunculated subserosal fibroid. During treatment, these pedunculated fibroids were targeted, while sparing the stalk connection between the fibroid and the uterus. Contrast-enhanced T1-weighted MR images were obtained immediately after the treatment to measure the nonperfused volume (NPV) ratio and to check stalk viability. Changes in tumor volume, diameter of the stalk, patient symptoms and adverse events were evaluated 6 months after treatment. RESULTS: The volume of the treated fibroids (n=9) ranged from 79-380cm(3) (mean, 198cm(3)), and NPV ratio ranged from 45%-80% (mean, 67%). MR imaging follow-up at 6 months showed a 14%-48% (mean, 30%) reduction in the volume of the treated fibroids (P =.008). In all cases, the pedunculated subserosal fibroids remained connected to the uterus with a 13% average decrease in the mean diameter of the stalks (from 3.5 to 3.0cm; P=.008). Eight of nine patients (89%) reported improvement in bulk-related fibroid symptoms after treatment. CONCLUSIONS: The results of this preliminary study suggest that MR imaging-guided focused US may be a safe and effective treatment for pedunculated subserosal fibroids. Larger prospective studies with longer follow-up are needed to confirm the suitability of MR imaging-guided focused US to treat this type of fibroid.