Humans are exposed to a complex mix of man-made electric and magnetic fields (MFs) at many different frequencies, at home and at work. Epidemiological studies indicate that there is a positive relationship between residential/domestic and occupational exposure to extremely low frequency electromagnetic fields and some types of cancer, although some other studies indicate no relationship. In this review, after an introduction on the MF definition and a description of natural/anthropogenic sources, the epidemiology of residential/domestic and occupational exposure to MFs and cancer is reviewed, with reference to leukemia, brain, and breast cancer. The in vivo and in vitro effects of MFs on cancer are reviewed considering both human and animal cells, with particular reference to the involvement of reactive oxygen species (ROS). MF application on cancer diagnostic and therapy (theranostic) are also reviewed by describing the use of different magnetic resonance imaging (MRI) applications for the detection of several cancers. Finally, the use of magnetic nanoparticles is described in terms of treatment of cancer by nanomedical applications for the precise delivery of anticancer drugs, nanosurgery by magnetomechanic methods, and selective killing of cancer cells by magnetic hyperthermia. The supplementary tables provide quantitative data and methodologies in epidemiological and cell biology studies. Although scientists do not generally agree that there is a cause-effect relationship between exposure to MF and cancer, MFs might not be the direct cause of cancer but may contribute to produce ROS and generate oxidative stress, which could trigger or enhance the expression of oncogenes.

The aim of this study was to compare the accuracy of multi-detector computed tomography (MDCT) with double contrast-enhanced ultrasound (DCEUS), in which intravenous microbubbles are used alongside oral contrast-enhanced ultrasound, in determining the gross classification of patients with gastric carcinoma (GC). Altogether, 239 patients with GC proved by histology after endoscopic biopsy were included in this study. DCEUS and MDCT were performed pre-operatively. The diagnostic accuracies of DCEUS and MDCT in determining the gross classification were calculated and compared. The overall accuracy of DCEUS in determining the gross appearance of GC was higher than that of MDCT (84.9% vs. 79.9%, p < 0.001). There was no significant difference in accuracy between DCEUS and MDCT for Borrmann I and IV classifications of advanced gastric cancer (χ(2), p = 0.323 for Borrmann type I, p = 0.141 for Borrmann type IV). The accuracy of DCEUS for early GC and Borrmann II and III classifications of GC was higher than that of MDCT (χ(2), p = 0.000 for all). DCEUS may be regarded as a valuable complementary tool to MDCT in determining the gross appearance of gastric adenocarcinoma pre-operatively.

The aim of this study was to prospectively compare the diagnostic performance of magnetic resonance imaging (MRI), multidetector computed tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative locoregional staging of gastric cancer.

This study had Institutional Review Board approval, and informed consent was obtained from all patients. Fifty-two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI, 64-channel MDCT and EUS. All images were analysed blind, and the results were compared with histopathological findings according to the seventh edition of the TNM classification. After the population had been divided on the basis of the local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity, specificity, positive and negative predictive value, and accuracy were calculated and diagnostic performance measures were assessed using the McNemar test.

For T staging, EUS showed higher sensitivity (94%) than MDCT and MRI (65 and 76%; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher specificity (91 and 89%) than EUS (60%) (p = 0.0009 and p = 0.003). Adding MRI to MDCT or EUS did not result in significant differences for sensitivity. For N staging, EUS showed higher sensitivity (92%) than MRI and MDCT (69 and 73%; p = 0.01 and p = 0.02). MDCT showed better specificity (81%) than EUS and MRI (58 and 73%; p = 0.03 and p = 0.15).

Our prospective study confirmed the leading role of EUS and MDCT in the staging of gastric cancer and did not prove, at present, the value of the clinical use of MRI.

To perform a meta-analysis and literature review regarding the diagnostic accuracy of MRI for pre-operative tumour depth invasion (T) and regional lymph node invasion (N) staging of gastric carcinoma (GC).

Articles were identified through systematic search of Medline, PubMed, Cochrane Library, Web of Science, Springerlink and several Chinese databases. The study quality was assessed by the quality assessment for studies of diagnostic accuracy. 2 reviewers independently extracted and assessed the data from 11 eligible studies. A meta-analysis was then carried out. Subgroup and sensitivity analyses were also performed.

11 studies (439 patients) were finally included in the current review. Among these studies, the significant evidence of heterogeneity was only discovered for specificity in T4 stage (I(2) = 59.8%). Pooled sensitivity and specificity of MRI to diagnose T stage tumour (T3-4 vs T1-2) were 0.93 [95% confidence interval (CI), 0.89-0.96] and 0.91 (95% CI, 0.87-0.95), respectively. Pooled estimates of sensitivity and specificity of MRI to diagnose N stage tumour (N0 vs N+) were 0.86 (95% CI, 0.80-0.92) and 0.67 (95% CI, 0.54-0.79), respectively. Subgroup analyses showed that diffusion-weighted imaging was more helpful for T staging.

The present systematic review suggests that MRI has a good diagnostic accuracy for pre-operative T staging of GC and should be widely used in clinical work. However, the ability for N staging is relatively poor on MRI.

In the pre-operative staging of GC, MRI was a useful tool and may enhance accuracy for the T staging of advanced GC.

Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic device for the locoregional staging of gastric cancer, which is crucial to developing a correct therapeutic strategy and ultimately to providing patients with the best chance of cure. However, despite a number of studies addressing this issue, there is no consensus on the role of EUS in routine clinical practice.

To provide both a comprehensive overview and a quantitative analysis of the published data regarding the ability of EUS to preoperatively define the locoregional disease spread (i.e., primary tumor depth (T-stage) and regional lymph node status (N-stage)) in people with primary gastric carcinoma.

We performed a systematic search to identify articles that examined the diagnostic accuracy of EUS (the index test) in the evaluation of primary gastric cancer depth of invasion (T-stage, according to the AJCC/UICC TNM staging system categories T1, T2, T3 and T4) and regional lymph node status (N-stage, disease-free (N0) versus metastatic (N+)) using histopathology as the reference standard. To this end, we searched the following databases: the Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE, EMBASE, NIHR Prospero Register, MEDION, Aggressive Research Intelligence Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), from 1988 to January 2015.

We included studies that met the following main inclusion criteria: 1) a minimum sample size of 10 patients with histologically-proven primary carcinoma of the stomach (target condition); 2) comparison of EUS (index test) with pathology evaluation (reference standard) in terms of primary tumor (T-stage) and regional lymph nodes (N-stage). We excluded reports with possible overlap with the selected studies.

For each study, two review authors extracted a standard set of data, using a dedicated data extraction form. We assessed data quality using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. We performed diagnostic accuracy meta-analysis using the hierarchical bivariate method.

We identified 66 articles (published between 1988 and 2012) that were eligible according to the inclusion criteria. We collected the data on 7747 patients with gastric cancer who were staged with EUS. Overall the quality of the included studies was good: in particular, only five studies presented a high risk of index test interpretation bias and two studies presented a high risk of selection bias.For primary tumor (T) stage, results were stratified according to the depth of invasion of the gastric wall. The meta-analysis of 50 studies (n = 4397) showed that the summary sensitivity and specificity of EUS in discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI 0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1 (early gastric cancer, EGC) versus T2 (muscle-infiltrating) tumors, the meta-analysis of 46 studies (n = 2742) showed that the summary sensitivity and specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93) respectively. When we addressed the capacity of EUS to distinguish between T1a (mucosal) versus T1b (submucosal) cancers the meta-analysis of 20 studies (n = 3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81 to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic involvement of lymph nodes (N-stage), the meta-analysis of 44 studies (n = 3573) showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to 0.87) and 0.67 (95% CI 0.61 to 0.72), respectively.Overall, as demonstrated also by the Bayesian nomograms, which enable readers to calculate post-test probabilities for any target condition prevalence, the EUS accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between-study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status.

By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings.

To determine the imaging detail and diagnostic information that can be obtained at 7.0-T magnetic resonance (MR) imaging with a voxel volume of 9.5-14.0 nL as a means of evaluating the depth of mural invasion by gastric carcinomas ex vivo.

This study was approved by the institutional review board, and written informed consent was obtained from each patient. Twenty gastric specimens containing 20 carcinomas were studied with a 7.0-T MR imaging system equipped with a four-channel surface coil. MR images were obtained with a 50-60 × 25-30 mm field of view, a 512 × 256 matrix, and a 1.0-mm section thickness, resulting in a voxel volume of 0.0095-0.0140 mm(3) (9.5-14.0 nL). The signal intensity of the gastric wall layers, tumor tissue, and fibrosis was described as low, intermediate, or high by comparing it with the signal intensity of the muscularis propria. Depth of invasion initially was assessed by two reviewers independently and then by the two reviewers in consensus. MR images were compared with histopathologic findings.

The 7.0-T T2-weighted MR images clearly depicted the normal gastric wall in all 20 specimens (100%) as consisting of seven layers, which clearly corresponded to the tissue layers of the gastric wall. These MR images enabled clear differentiation between tumor tissue and fibrosis. Reviewers disagreed on the depth of invasion at the initial reading in three (15%) of 20 specimens (between mucosa and submucosa in two specimens and between muscularis propria and subserosa and serosa in one specimen); however, in all 20 gastric carcinomas, the depth of invasion could be accurately determined on T2-weighted images after consensus interpretation.

Ex vivo 7.0-T MR imaging enables clear delineation of the gastric wall layers and clear differentiation of tumor tissue from fibrosis and allows one to assess the depth of mural invasion by gastric carcinomas.

A system which allows magnetic resonance (MR) and ultrasound (US) image data to be acquired simultaneously has been developed. B-mode and Doppler US were performed inside the bore of a clinical 1.5 T MRI scanner using a clinical 1-4 MHz US transducer with an 8-metre cable. Susceptibility artefacts and RF noise were introduced into MR images by the US imaging system. RF noise was minimised by using aluminium foil to shield the transducer. A study of MR and B-mode US image signal-to-noise ratio (SNR) as a function of transducer-phantom separation was performed using a gel phantom. This revealed that a 4 cm separation between the phantom surface and the transducer was sufficient to minimise the effect of the susceptibility artefact in MR images. MR-US imaging was demonstrated in vivo with the aid of a 2 mm VeroWhite 3D-printed spherical target placed over the thigh muscle of a rat. The target allowed single-point registration of MR and US images in the axial plane to be performed. The system was subsequently demonstrated as a tool for the targeting and visualisation of high intensity focused ultrasound exposure in the rat thigh muscle.

The role of EUS in the locoregional staging of gastric carcinoma is undefined.

We aimed to comprehensively review and quantitatively summarize the available evidence on the staging performance of EUS.

We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for relevant studies published until July 2010.

Formal meta-analysis of diagnostic accuracy parameters was performed by using a bivariate random-effects model.

Fifty-four studies enrolling 5601 patients with gastric cancer undergoing disease staging with EUS were eligible for the meta-analysis.

EUS staging accuracy across eligible studies was measured by computing overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).

EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI, 0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI, 0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic performance of EUS for lymph node status is less reliable, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84 (95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95% CI, 9-16), respectively. Results regarding single T categories (including T1 substages) and Bayesian nomograms to calculate posttest probabilities for any target condition prevalence are also provided.

Statistical heterogeneity was generally high; unfortunately, subgroup analysis did not identify a consistent source of the heterogeneity.

Our results support the use of EUS for the locoregional staging of gastric cancer, which can affect the therapeutic management of these patients. However, clinicians must be aware of the performance limits of this staging tool.

The clinical value of double contrast-enhanced ultrasonography (DCUS) in determining the Lauren classification of advanced gastric carcinoma needed investigation.

Fifty-eight patients with gastric cancer proved by endoscopic biopsy underwent preoperative DCUS examination in which an oral contrast agent was combined with an intravenous agent, and the findings were compared with the postoperative pathological findings using haematoxylin-eosin and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining.

Of 58 patients, 34 (59%) were the intestinal type and 24 (41%) the diffuse type on pathological examination of resected specimens. Among intestinal type patients, 30 (88%) showed homogeneous vascular enhancement and 4 (12%) heterogeneous enhancement with the "sandwich" pattern in 2 patients (50%) and "barrier" pattern in 2 patients (50%). In the diffuse type, 22 of 24 patients (92%) enhanced heterogeneously, with stippled and peripheral enhancement in 9 (41%), the "sandwich" pattern in 8 (36%) and "barrier" pattern in 5 (23%). Two of 24 patients (8%) with the diffuse type enhanced homogeneously. The proportion of heterogeneous enhancement was significantly different between the 2 subtypes of tumour (p = 0.0001). The sensitivity and specificity of heterogeneous enhancement in diagnosing the diffuse type of advanced gastric cancer were 92% and 88%, respectively. Youden's index was 0.8.

Double contrast-enhanced ultrasonography is a new and useful method to determine Lauren classification in patients with gastric carcinoma.

Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy.

Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer.

Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA.

Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.