Background & Aims In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal ...junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. Methods We performed a study of 24 healthy, Helicobacter pylori –negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. Results The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). Conclusions Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.
Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to ...determine whether it may be due to columnar metaplasia of the distal oesophagus.
We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver-intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording.
Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001).
These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.
Aims/hypothesis
South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic ...depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors.
Methods
We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries (
https://osf.io/w5bf9
).
Results
We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5–0.7 kg/m
2
lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55;
I
2
=83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98;
I
2
=93%) more liver fat, but nine studies had similar VAT (−0.03 SMD; 95% CI −0.24, 0.19;
I
2
=85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m
2
lower BMI but 0.31 SMD (95% CI 0.14, 0.48;
I
2
=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI −0.17, 0.23;
I
2
=72%) and VAT levels (0.04 SMD; 95% CI −0.16, 0.24;
I
2
=71%) did not differ significantly between ethnic groups in eight studies of women.
Conclusions/interpretation
South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians.
Funding
There was no primary direct funding for undertaking the systematic review and meta-analysis.
Graphical abstract
To investigate the necessity of performing MRI in the radiotherapy position when using MRI for prostatic radiotherapy.
20 prostate patients received a CT, diagnostic MRI and an MRI scan in the ...radiotherapy position. The quality of registration between CT and MRI was compared between the two MRI set-ups. The prostate and seminal vesicles were contoured using all scans and intensity modulated radiotherapy (IMRT) plans were generated. Changes in the target volume and IMRT plans were investigated. Two-tailed paired Student's t-tests determined the statistical significance.
There was a decrease in the mean distance from the centre of the bony anatomy between CT and MRI (from 3.9 to 1.9 mm, p-value<0.0001) when the MRI scan was acquired in the radiotherapy position. Assuming that registering CT with an MRI scan in the radiotherapy position is the gold standard for delineating the prostate and seminal vesicles, using a planning target volume delineated on the CT with a diagnostic MRI scan viewed separately, resulted in a mean conformation number of 0.80 instead of the expected 0.98 (p<0.0001).
By registering CT with an MRI scan in the radiotherapy position, there is a statistically significant improvement in the registration and IMRT quality.
To achieve an acceptable registration and IMRT quality in prostatic radiotherapy, neither CT with a separate diagnostic MRI nor CT registered to a diagnostic MRI will suffice. Instead, a CT registered with an MRI in the radiotherapy position should be used.
This study compared plans of high definition (HD), 2.5 mm width multi-leaf collimator (MLC), to standard, 5 mm width, isocentric linear accelerator (linacs), CyberKnife (CK), and Gamma Knife (GK) for ...stereotactic radiosurgery (SRS) techniques on multiple brain metastases.
Eleven patients undergoing SRS for multiple brain metastases were chosen. Targets and organs at risk (OARs) were delineated and optimized SRS plans were generated and compared.
The linacs delivered similar conformity index (CI) values, but the gradient index (GI) for HD MLCs was significantly lower (
-value <.001). Half the OARs received significantly lower dose using HD MLCs. CK delivered a significantly lower CI than HD MLC linac (
-value <.001), but a significantly higher GI (
-value <.001). CI was significantly improved with the HD MLC linac compared to GK (
-value = 4.591 × 10
), however, GK delivered a significantly lower GI (
-value <.001). OAR dose sparing was similar for the HD MLC TL, CK, and GK.
Comparing linacs for SRS, the preferred choice is HD MLCs. Similar results were achieved with the HD MLC linac, CK, or GK, with each delivering significant improvements in different aspects of plan quality.
This article is the first to compare HD and standard width MLC linac plans using a combination of single isocentre volumetric modulated arc therapy and multi-isocentric dynamic conformal arc plans as required, which is a more clinically relevant assessment. Furthermore, it compares these plans with CK and GK, assessing the relative merits of each technique.
The purpose of this study was to demonstrate how magnetic resonance imaging (MRI) patient position protocols influence registration quality in patients with oropharyngeal cancer undergoing radical ...radiotherapy and the consequences for gross tumour volume (GTV) definition and radiotherapy planning.
Twenty-two oropharyngeal patients underwent a computed tomography (CT), a diagnostic MRI (MRI(D)) and an MRI in the radiotherapy position within an immobilization mask (MRI(RT)). Clinicians delineated the GTV on the CT viewing the MRI(D) separately (GTV(C)); on the CT registered to MRI(D) (GTV(D)) and on the CT registered to MRI(RT) (GTV(RT)). Planning target volumes (PTVs) were denoted similarly. Registration quality was assessed by measuring disparity between structures in the three set-ups. Volumetric modulated arc therapy (VMAT) radiotherapy planning was performed for PTV(C), PTV(D) and PTV(RT). To determine the dose received by the reference PTV(RT), we optimized for PTV(C) and PTV(D) while calculating the dose to PTV(RT). Statistical significance was determined using the two-tailed Mann-Whitney or two-tailed paired student t-tests.
A significant improvement in registration accuracy was found between CT and MRI(RT) versus the MRI(D) measuring distances from the centre of structures (geometric mean error of 2.2 mm versus 6.6 mm). The mean GTV(C) (44.1 cm3) was significantly larger than GTV(D) (33.7 cm3, p value = 0.027) or GTV(RT) (30.5 cm3, p value = 0.014). When optimizing the VMAT plans for PTV(C) and investigating the mean dose to PTV(RT) neither the dose to 99% (58.8%) nor 95% of the PTV (84.7%) were found to meet the required clinical dose constraints of 90% and 95% respectively. Similarly, when optimizing for PTV(D) the mean dose to PTV(RT) did not meet clinical dose constraints for 99% (14.9%) nor 95% of the PTV (66.2%). Only by optimizing for PTV(RT) were all clinical dose constraints achieved.
When oropharyngeal patients MRI scans are performed in the radiotherapy position there are significant improvements in CT-MR image registration, target definition and PTV dose coverage.
The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability ...using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.
MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra- and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.
The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.
The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.
The purpose of this thesis is to develop the role of magnetic resonance imaging (MRI) in the radiotherapy (RT) planning process. This began by assessing a prototype inline three-dimensional ...distortion correction algorithm. A number of quality assurance tests were conducted using different test objects and the 3D distortion correction algorithm was compared with the standard two-dimensional version available for clinical use on the MRI system. Scanning patients using MRI in the RT position within an immobilisation mask can be problematic, since the multi-channel head coils typically used in diagnostic imaging, are not compatible with the immobilisation mask. To assess the image quality which can be obtained with MR imaging in the RT position, various MRI quality assurance phantoms were positioned within an immobilisation mask and a series of image quality tests were performed on four imaging coils compatible with the immobilisation mask. It was shown that only the 4-channel cardiac coil delivered comparable image quality to a multi-channel head coil. An investigation was performed to demonstrate how MRI patient position protocols influence registration quality in patients with prostate cancer undergoing radical RT. The consequences for target volume definition and dose coverage with RT planning were also assessed. Twenty patients with prostate cancer underwent a computed tomography (CT) scan in the RT position, a diagnostic MRI scan and an MRI scan in the RT position. The CT datasets were independently registered with the two MRI set-ups and the quality of registration was compared. This study demonstrated that registering CT and MR images in the RT position provides a statistically significant improvement in registration quality, target definition and target volume dose coverage for patients with prostate cancer. A similar study was performed on twenty-two patients with oropharyngeal cancer undergoing radical RT. It was shown that when patients with oropharyngeal cancer undergo an MRI in the RT position there are significant improvements in CT-MR image registration, target definition and target volume dose coverage.
The purpose of this thesis is to develop the role of magnetic resonance imaging (MRI) in the radiotherapy (RT) planning process. This began by assessing a prototype inline three-dimensional ...distortion correction algorithm. A number of quality assurance tests were conducted using different test objects and the 3D distortion correction algorithm was compared with the standard two-dimensional version available for clinical use on the MRI system. Scanning patients using MRI in the RT position within an immobilisation mask can be problematic, since the multi-channel head coils typically used in diagnostic imaging, are not compatible with the immobilisation mask. To assess the image quality which can be obtained with MR imaging in the RT position, various MRI quality assurance phantoms were positioned within an immobilisation mask and a series of image quality tests were performed on four imaging coils compatible with the immobilisation mask. It was shown that only the 4-channel cardiac coil delivered comparable image quality to a multi-channel head coil. An investigation was performed to demonstrate how MRI patient position protocols influence registration quality in patients with prostate cancer undergoing radical RT. The consequences for target volume definition and dose coverage with RT planning were also assessed. Twenty patients with prostate cancer underwent a computed tomography (CT) scan in the RT position, a diagnostic MRI scan and an MRI scan in the RT position. The CT datasets were independently registered with the two MRI set-ups and the quality of registration was compared. This study demonstrated that registering CT and MR images in the RT position provides a statistically significant improvement in registration quality, target definition and target volume dose coverage for patients with prostate cancer. A similar study was performed on twenty-two patients with oropharyngeal cancer undergoing radical RT. It was shown that when patients with oropharyngeal cancer undergo an MRI in the RT position there are significant improvements in CT-MR image registration, target definition and target volume dose coverage.
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