Investigation of clinical utility of contrast-enhanced MRI in the diagnosis of ectopic pregnancy.

AIM: To investigate whether contrast-enhanced (CE)-magnetic resonance imaging (MRI) improves identification of implantation site of ectopic pregnancy. MATERIALS AND METHODS: This retrospective study enrolled 63 patients in whom implantation sites had been confirmed at histopathology. Two expert radiologists for gynaecological imaging and two inexpert radiologists independently reviewed non-CE MRI and a combination of non-CE and CE-MRI (non-CE+CE-MRI), then determined implantation site with a confidence level. The following MRI features were also evaluated: extrauterine gestational sac (GS)-like structure (shape, signal intensities at T1-weighted imaging [WI], T2WI, and diffusion-weighted imaging [DWI], presence of the three rings appearance, and distinct low intensity areas at T2WI, presence of tree or dot-like components, degree of contrast enhancement), fallopian tube (dilatation, dilatation with haematoma, degree of contrast enhancement, enhanced components within the tube), and ascites. These findings were compared for non-CE and non-CE+CE-MRI data, and for expert and inexpert groups. RESULTS: The expert group identified implantation sites correctly in 58/63 (92%) cases for non-CE and non-CE+CE-MRI. In the inexpert group, the correct identification was improved from 54/63 (86%) using non-CE MRI to 58/63 (92%) using non-CE+CE-MRI, but was not significant (p=0.29). In comparison between non-CE and non-CE+CE-MRI, dilation of the fallopian tubes was observed more frequently (p=0.004) and the confidence level was elevated significantly in the non-CE+CE-MRI (p<0.0001) in the inexpert group. Intergroup comparison revealed that confidence level was significantly higher in the expert group than in the inexpert group using non-CE MRI (p<0.0001), although the difference was not significant at non-CE+CE MRI (p=0.49). CONCLUSION: CE-MRI did not significantly improve correct identification of ectopic pregnancy implantation sites, although the addition of contrast enhancement did enable inexpert radiologists to diagnose confidently.

Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis.

Endometriosis is a common gynaecological condition of unknown aetiology that primarily affects women of reproductive age. The accepted first-line imaging modality is pelvic ultrasound. However, magnetic resonance imaging (MRI) is increasingly performed as an additional investigation in complex cases and for surgical planning. There is currently no international consensus regarding patient preparation, MRI protocols or reporting criteria. Our aim was to develop clinical guidelines for MRI evaluation of pelvic endometriosis based on literature evidence and consensus expert opinion. This work was performed by a group of radiologists from the European Society of Urogenital Radiology (ESUR), experts in gynaecological imaging and a gynaecologist expert in methodology. The group discussed indications for MRI, technical requirements, patient preparation, MRI protocols and criteria for the diagnosis of pelvic endometriosis on MRI. The expert panel proposed a final recommendation for each criterion using Oxford Centre for Evidence Based Medicine (OCEBM) 2011 levels of evidence. KEY POINTS: • This report provides guidelines for MRI in endometriosis. • Minimal and optimal MRI acquisition protocols are provided. • Recommendations are proposed for patient preparation, best MRI sequences and reporting criteria.

3 T MRI uterine peristalsis: comparison of symptomatic fibroid patients versus controls.

AIM: To compare uterine peristalsis between symptomatic fibroid patients and normal subjects and to determine the possible effect of fibroid characteristics on uterine peristalsis at high-field magnetic resonance imaging (MRI). MATERIALS AND METHODS: The present study included 20 symptomatic fibroid patients (age range 39-53 years) and 20 normal subjects (age range 19-46 years). MRI images were obtained during the peri-ovulatory phase using 3 T MRI using a sagittal T2 turbo spin-echo sequence and a half-Fourier acquisition single-shot turbo spin-echo sequence for display on cine mode. Two radiologists independently evaluated the images for the presence of uterine peristalsis by confidence level. In cases where peristalsis was present, the images were also evaluated for peristalsis frequency and direction. For fibroid patients, uterine and index fibroid volume, fibroid burden and index fibroid location were also recorded. RESULTS: Uterine peristalsis was significantly decreased in symptomatic fibroid patients compared with normal controls (p < 0.01). Peristalsis frequency in fibroid patients was also lower than in normal subjects. Direction of peristalsis was cervix-to-fundus for the majority of fibroid patients and controls. There was no significant relationship between fibroid characteristics, such as uterine volume, index fibroid volume, index fibroid location, and fibroid number in fibroid patients with, and fibroid patients without peristalsis. CONCLUSION: In women with symptomatic fibroids, the presence of uterine peristalsis is significantly decreased compared to normal controls on 3 T cine MRI. The presence of fibroids appears to disturb the normal conduction of uterine peristalsis and may interfere with fluid (e.g., menses, sperm) transport.

Effect of adjuvant chemotherapy on localized dedifferentiated low-grade osteosarcoma: a systematic review.

PURPOSE: Dedifferentiated low-grade osteosarcomas, which are considered high grade malignancies, can arise from the dedifferentiation of parosteal and low-grade osteosarcomas. Usually, localized dedifferentiated low-grade osteosarcomas are treated by wide resection, and the efficacy of adjuvant chemotherapy is controversial. We conducted a systematic review of studies that investigated the rates of mortality and significant events, such as recurrence and metastases, in localized dedifferentiated low-grade osteosarcoma patients who received wide resection only and in those who received wide resection and (neo-)adjuvant chemotherapy. METHODS: We identified 712 studies through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials databases. Of those studies, seven were included in this review and none were randomized controlled trials. In the seven studies, 114 localized dedifferentiated low-grade osteosarcoma patients were examined. RESULTS: Mortality rates of the resection plus chemotherapy (R + C) and the resection only (Ronly) groups were 20.3% and 11.4%, respectively [overall pooled odds ratio, 1.59 (P = 0.662); heterogeneity I2, 0%]. The local recurrence or distant metastasis rate in the R + C group was 36.7% and that in the Ronly group was 28.6% [overall pooled odds ratio, 1.37 (P = 0.484); heterogeneity I2 was 0%]. CONCLUSIONS: Results show a limited efficacy of adjuvant chemotherapy for localized dedifferentiated low-grade osteosarcoma. However, because this was a systematic review of retrospective studies that examined a small number of patients, future randomized controlled trials are needed.

Whole-heart coronary MR angiography under a single breath-hold: a comparative study with respiratory-gated acquisition using a multi-element phased-array coil.

AIM: To compare visualization using whole-heart coronary magnetic resonance angiography (CMRA) acquired during a single breath-hold (BH) with that using conventional respiratory-gated (RG) CMRA. MATERIALS AND METHODS: The CMRAs of 14 healthy subjects under either BH or RG conditions were studied using a 1.5 T system equipped with a whole-body phased-array coil and 16-channel receivers. The BH examination was accelerated using parallel imaging (PI) by factors of 2.5 and 2 in the phase and section directions, respectively. For the RG examination, a PI factor of 2 was used only in the phase direction. The visualization quality of 15 coronary segments using each condition was evaluated with a five-point scale (0-4). Differences between two conditions were compared at segments with an average score greater than 2 in RG-CMRA. RESULTS: The average examination time for BH and RG acquisition scans was 34 s and 11 min 31 s, respectively. Ten segments (segments 1-3, 5-9, 11, and 13) had average scores higher than 2 in RG-CMRA. Of these, BH-CMRA had significantly lower scores than RG-CMRA at six segments (segments 1, 5-8, and 11) after correction for multiple comparisons (p<0.005). However, in BH-CMRA, proximal segments (segments 1-2, 5-7, and 11) showed average scores over 2, indicating marginally acceptable image quality. CONCLUSION: Compared with the relatively limited degree of image degradation with RG-CMRA, the present data suggest that BH-CMRA would be useful for screening and as an adjunct to RG-CMRA that is occasionally incomplete.

Physiological uptake of 18F-fluorodeoxyglucose in uterine endometrium and myometrium: correlation with uterine motility evaluated by cine magnetic resonance imaging.

BACKGROUND: Accumulation of (18)F-fluorodeoxyglucose ((18)F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. PURPOSE: To investigate the relationship between radiometabolic activity of (18)F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. RESULTS: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32+/-1.47) than in those without contractions (2.45+/-0.66). CONCLUSION: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium.

Animal model of depression. III. Mechanism of action of tetrabenazine.

A study was undertaken to gain an understanding of the biochemical mechanism whereby tetrabenazine (TBZ) produces a sedative effect on the locomotor activity of rats. Rats injected with L-5-hydroxytryptophan (L-5-HTP, 30 mg/kg), the immediate precursor of 5-hydroxytryptamine (5-HT), showed the characteristic bison appearance, pitosis, and catalepsy normally observed after injecting TBZ (30 mg/kg). The treatment of rats with low doses of L-5-HTP (9 mg/kg) plus TBZ (2 mg/kg) significantly decreased locomotor activity, whereas low doses of either one of these drugs given alone had no significant effect on locomotor activity. The level of 5-hydroxyindoleacetic acid (5-HIAA) was elevated in the brain of rats sacrificed 3 hr after treatment with low doses of either L-5-HTP or TBZ alone. Treatment of rats with p-chlorophenylalanine to inhibit the synthesis of 5-HT had an inhibitory effect on the duration of sedation following an injection of TBZ (30 mg/kg). The results of the biochemical and pharmacological studies as reflected by changes in locomotor activity were interpreted to indicate that the sedative action of TBZ was due to an excess of functional 5-HT.

Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines.

This study aimed at clarifying the role of Aminopeptidase N (APN), a Zn2+-dependent ectopeptidase localized on the cell surface of human osteosarcoma cell lines treated with proinflammatory cytokines. We investigated the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) as well as the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) for their influence on APN regulation. Soluble IL-6 receptor (sIL-6R) was always used together with IL-6 to achieve a stable effect. In addition, the invasive potential of the osteosarcoma cell lines MG63 and HOS was examined. Competitive RT-PCR and Ala-pNA activity assays revealed that IL-6 and sIL-6R significantly increased the mRNA expression and activity of APN in both osteosarcoma cell lines. Although IL-1beta significantly stimulated APN mRNA expression in both cell lines, it influenced the enzyme activity only in MG63. TNF-alpha and TGF-beta, however, had an effect neither on mRNA expression nor on the enzyme activity of APN in both cell lines. In the Matrigel invasion assay, IL-6 and sIL-6R significantly up-regulated the transmigration of these cell lines, whereas other cytokines did not. The up-regulated invasion was inhibited by bestatin, a specific inhibitor of APN. Cellular migration correlated highly with APN activity (r = 0.79, P < 0.002). These findings suggest that APN contributes to the invasive potential of human osteosarcomas enhanced by IL-6 and SIL-6R.

Delay in administration of CDDP until completion of AGM-1470 treatment enhances antimetastatic and antitumor effects.

The efficacy of cis-diammine dichloroplatinum (CDDP) therapy in combination with continuous administration of angiogenesis inhibitor o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line previously established in our laboratory. AGM-1470 (2.5 mg/kg body weight/week) was administered by Alzet osmotic pumps for 2 weeks starting from 7 days after tumor inplantation and CDDP (1.25 mg/kg) was given on days 21 and 24. The number of lung metastatic nodules was counted and the wet weights of the primary tumors were measured 5 weeks after tumor inplantation. Values with administration of CDDP 3 days after discontinuation of AGM-1470 were significantly lower than when the two agents were coadministered (P < 0.05). This animal model should facilitate optimization of the timing of combination therapy.

Marked thyroid uptake of thallium-201 in patients with goiter: case report.

Marked thyroid uptake of thallium-201 was observed in four patients with goiter, namely one case each of hyperthyroidism, primary hypothyroidism due to chronic thyroiditis, chronic thyroiditis in the mild hypothyroid state, and nontoxic nodular goiter.

Uptake of thallium-201 in enlarged thyroid glands: concise communication.

We have investigated the thyroid uptake of Tl-201 in 37 patients with various types of goiter, and in six with normal thyroids. Significant thallium uptake was found in all cases in which there was thyroid enlargement, including Graves' disease, toxic thyroid nodule, primary hypothyroidism, simple goiter, Hashimoto's disease, thyroid carcinoma, and thyroid adenoma. If goiter was absent, however, there was no demonstrable uptake--e.g., in secondary hypothyroidism, subacute thyroiditis, and the normal controls. Thallium uptake did not correlate with thyroid function tests such as BMR, T3-RU, T3, T4, TSH, antithyroid antibodies, or the 24-hr I-131 uptake. In 23 patients with diffuse goiter, on the other hand, maximum Tl-201 uptake correlated well with thyroid weight: r = 0.836 (p less than 0.001); y = 0.02 x + 0.06.

Increased telomerase activity is not directly related to metastatic potential in rat transplantable osteosarcomas.

Previously, we reported the establishment of two transplantable osteosarcomas in rats, one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1-oxide (4-HAQO), and another which developed spontaneously, and their subdivision into four lines with high and low metastatic potential to the lung. In the present study, activation of telomerase was investigated by the telomeric repeat amplification protocol (TRAP) assay followed by densitometric quantification. Telomerase activity was found to be elevated in all four lines without any link to the metastatic potential. Thus the spontaneous osteosarcoma (SOS) and derived metastatic lesions (S-SLM) demonstrated a 20.1-23.5-fold increase and the chemical carcinogen (4HAQO)-induced osteosarcoma (COS) and metastatic lesions (C-SLM) were 18.4-19.1-fold elevated as compared to the value for abdominal muscle. The results suggest that activation of telomerase occurs in rat osteosarcomas but that it is not directly involved in determining their metastatic potential.

Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats.

In the present experiment, the expression of matrix metalloproteinase (MMP)-2 and MMP-9, key proteins in the MMP family, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, antagonistic proteins against MMP-2 and MMP-9, respectively, were investigated by Northern blot analysis in rat transplantable osteosarcomas with high and low metastatic potencies. Two transplantable osteosarcomas, one induced with the carcinogen, 4-hydroxyaminoquinoline 1-oxide (4-HAQO) (COS, chemical carcinogen-induced osteosarcoma), and the other, a spontaneous lesion (SOS, spontaneous osteosarcoma), were repeatedly transplanted from lung nodules to generate lines with high metastatic potency, C-SLM (chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions) and S-SLM (spontaneous osteosarcoma, selected lung metastatic lesions), respectively. MMP-9 was overexpressed in both S-SLM and C-SLM, and TIMP-2 in the case of S-SLM. Neither MMP-2 nor TIMP-1 was overexpressed in either of the transplantable osteosarcomas with high metastatic potentials. The active form MMP-9, studied by zymography, increased in S-SLM and C-SLM but not in SOS and COS. MMP-9 mRNA expression was highly correlated with the gelatinolytic activity of active form MMP-9 (r = 0.85, P < 0.0001) and with the activation ratio of MMP-9 (r = 0.83, P < 0.0001). However, the active form MMP-2 was not detectable in all cases. These results suggest that overexpression of MMP-9 mRNA is one of the essential factors in the acquisition of metastatic potential in rat transplantable osteosarcomas.

p53 mutation and absence of mdm2 amplification and Ki-ras mutation in 4-hydroxyamino quinoline 1-oxide induced transplantable osteosarcomas in rats.

Previously, we reported the establishment of two transplantable osteosarcomas, one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1-oxide(4-HAQO), and another which developed spontaneously in rats, and their subdivision into four lines with high and low metastatic potential to the lung. In the present study, mutations of p53 and Ki-ras genes were investigated by PCR and SSCP followed by direct sequencing, and the amplification of the mdm2 gene was assessed by Southern blot analysis. Mutations of p53 in exon 7 were detected in 4-HAQO-induced transplantable osteosarcomas, but not their spontaneous counterparts, irrespective of the metastatic potentials. Direct sequencing revealed a CGC to CAC transition with an amino acid change of Arg to His, at codon 246. Neither Ki-ras mutations nor mdm2 amplification were detected in any of the transplantable tumors. The results suggest that while p53 mutations occurred during osteosarcoma development by 4-HAQO without mdm2 amplification and Ki-ras mutation does not contribute to osteosarcoma development in rats.

Induction of telomerase activity during regeneration after partial hepatectomy in the rat.

The regulation of telomerase activity during regeneration induced by two-thirds partial hepatectomy (PH) was investigated in 6-week-old male F344 rats. Groups of animals were serially sacrificed 0, 6, 16, 24, 36 and 72 h after the operation and telomerase activity was determined by the telomeric repeat amplification protocol (TRAP) assay followed by densitometric quantification. DNA synthesis was immunohistochemically quantified in terms of bromodeoxyuridine (BrdU) incorporation. The expression levels of telomerase RNA were examined by Northern blot analysis. Telomerase activity was increased significantly from 6 to 36 h but had decreased to close to the normal levels after 72 h. DNA synthesis reached a maximum 24 h after PH. However, the expression levels of telomerase RNA did not change during regeneration. The results suggest that telomerase is actively regulated by unknown mechanisms throughout the cell cycle in regenerating rat hepatocytes.

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.

Mutations of Ki-ras and p53 genes in hepatocellular carcinomas (HCCs) induced by the choline deficient L-amino acid defined (CDAA) diet in rats were investigated by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis followed by direct sequencing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 70 weeks and then sacrificed. Macroscopically detectable nodules which were histologically confirmed to be well-differentiated HCCs were dissected free from the surrounding tissue and subjected to gene mutation analysis along with samples of non-tumor areas. Conformational change in the Ki-ras gene was detected in 1 out of 7 HCCs, involving a GGC to GTC transversion at codon 13. No p53 mutations were detected in 7 HCCs and also neither Ki-ras nor p53 mutations were found in non-tumor areas. The results suggest that neither Ki-ras nor p53 genes play an important role in hepatocarcinogenesis caused by long term expose to a CDAA diet in rats.

Heterogeneous pattern of gene expression in cloned cell lines established from a rat transplantable osteosarcoma lung metastatic nodule.

We have established three cloned cell lines (COS1NR, COS2NR and COS4NR) from the lung metastatic nodule of a highly metastatic variant of rat transplantable osteosarcoma, C-SLM. All three clones shared the same morphological characteristics and tumorigenicity, but their growth rates in vitro and metastatic ability in vivo differed from each other. Single-strand conformation polymorphism (SSCP) analysis revealed all three clones to have the same p53 gene mutation and parent C-SLM tumor. On the other hand, Northern blot analysis showed a different pattern of expression for the genes, c-fos, c-jun, c-Ha-ras, transin (rat stromelysin), bone Gla protein (osteocalsin) and nm23/NDP kinase. These results indicate the presence of a heterogeneous cell population in terms of the different pattern of gene expression in a lung metastatic nodule of rat osteosarcoma and the present newly established cell lines will be useful for further investigation of the biological behavior of osteosarcomas.

Increased telomerase activity and absence of p53 mutation in oligoastrocytomas induced by N-ethyl-N-nitrosourea in rats.

The question of whether the changes in telomerase activity and/or the alteration of the p53 gene are involved in the development of oligo-astrocytomas induced by N-ethyl-N-nitrosourea (ENU) in rats was addressed. Telomerase activity levels of oligo-astrocytomas, including early neoplastic lesions, were significantly increased as compared to the normal controls, correlating with the degree of malignancy. In contrast, no mutations of p53 exons 5-7 were found in early neoplastic lesions or oligo-astrocytomas. These results indicate that the activation of telomerase occurs during astrocytoma carcinogenesis and contributes to the development of brain tumors, but the alterations of p53, at least on exons 5-7, may not be involved in this process.