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1.  Whole-liver CT texture analysis in colorectal cancer: Does the presence of liver metastases affect the texture of the remaining liver? 
Liver metastases limit survival in colorectal cancer. Earlier detection of (occult) metastatic disease may benefit treatment and survival.
The objective of this article is to evaluate the potential of whole-liver CT texture analysis of apparently disease-free liver parenchyma for discriminating between colorectal cancer (CRC) patients with and without hepatic metastases.
The primary staging CT examinations of 29 CRC patients were retrospectively analysed. Patients were divided into three groups: patients without liver metastases (n = 15), with synchronous liver metastases (n = 10) and metachronous liver metastases within 18 months following primary staging (n = 4). Whole-liver texture analysis was performed by delineation of the apparently non-diseased liver parenchyma (excluding metastases or other focal liver lesions) on portal phase images. Mean grey-level intensity (M), entropy (E) and uniformity (U) were derived with no filtration and different filter widths (0.5 = fine, 1.5 = medium, 2.5 = coarse).
Mean E1.5 and E2.5 for the whole liver in patients with synchronous metastases were significantly higher compared with the non-metastatic patients (p = 0.02 and p = 0.01). Mean U1.5 and U2.5 were significantly lower in the synchronous metastases group compared with the non-metastatic group (p = 0.04 and p = 0.02). Texture parameters for the metachronous metastases group were not significantly different from the non-metastatic group or synchronous metastases group (p > 0.05), although – similar to the synchronous metastases group – there was a subtle trend towards increased E1.5, E2.5 and decreased U1.5, U2.5 values. Areas under the ROC curve for the diagnosis of synchronous metastatic disease based on the texture parameters E1.5,2.5 and U1.5,2.5 ranged between 0.73 and 0.78.
Texture analysis of the apparently non-diseased liver holds promise to differentiate between CRC patients with and without metastatic liver disease. Further research is required to determine whether these findings may be used to benefit the prediction of metachronous liver disease.
PMCID: PMC4245301  PMID: 25452849
Colorectal cancer; liver metastases; CT texture; occult disease; metachronous metastases
2.  The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery 
BMC Surgery  2011;11:34.
The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer.
Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.
Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol.
The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at (NCT01273051)
PMCID: PMC3295682  PMID: 22171697
3.  Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability 
European Radiology  2011;21(12):2567-2574.
To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC).
Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6–8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC).
ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs.
ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results.
Key Points
• ROI size and positioning influence tumour ADC measurements in rectal cancer
• ROI size and positioning influence interobserver variability of tumour ADC measurements
• ADC measurements of the whole tumour volume provide the most reproducible results
• Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment
• Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response
PMCID: PMC3217149  PMID: 21822946
Diffusion magnetic resonance imaging; Rectal neoplasms; Observer variation; Methodology; Apparent diffusion coefficient
4.  T-staging of rectal cancer: accuracy of 3.0 Tesla MRI compared with 1.5 Tesla 
Abdominal Imaging  2011;37(3):475-481.
Magnetic resonance imaging (MRI) is not accurate in discriminating T1-2 from borderline T3 rectal tumors. Higher resolution on 3 Tesla-(3T)-MRI could improve diagnostic performance for T-staging. The aim of this study was to determine whether 3T-MRI compared with 1.5 Tesla-(1.5T)-MRI improves the accuracy for the discrimination between T1-2 and borderline T3 rectal tumors and to evaluate reproducibility.
13 patients with non-locally advanced rectal cancer underwent imaging with both 1.5T and 3T-MRI. Three readers with different expertise evaluated the images and predicted T-stage with a confidence level score. Receiver operator characteristics curves with areas under the curve (AUC) and diagnostic parameters were calculated. Inter- and intra-observer agreements were calculated with quadratic kappa-weighting. Histology was the reference standard.
Seven patients had pT1-2 tumors and six had pT3 tumors. AUCs ranged from 0.66 to 0.87 at 1.5T vs. 0.52–0.82 at 3T. Mean overstaging rate was 43% at 1.5T and 57% at 3T (P = 0.23). Inter-observer agreement was κ 0.50–0.71 at 1.5T vs. 0.15–0.68 at 3T. Intra-observer agreement was κ 0.71 at 1.5T and 0.76 at 3T.
This is the first study to compare 3T with 1.5T MRI for T-staging of rectal cancer within the same patients. Our results showed no difference between 3T and 1.5T-MRI for the distinction between T1-2 and borderline T3 tumors, regardless of expertise. The higher resolution at 3T-MRI did not aid in the distinction between desmoplasia in T1-2-tumors and tumor stranding in T3-tumors. Larger studies are needed to acknowledge these findings.
PMCID: PMC3345180  PMID: 21674192
Rectal cancer; MRI; T-stage; 3 Tesla; Medicine & Public Health; Hepatology; Gastroenterology; Imaging / Radiology
5.  What is the most accurate whole-body imaging modality for assessment of local and distant recurrent disease in colorectal cancer? A meta-analysis 
The objective of this study was to compare the diagnostic performance of positron emission tomography (PET), PET/CT, CT and MRI as whole-body imaging modalities for the detection of local and/or distant recurrent disease in colorectal cancer (CRC) patients who have a (high) suspicion of recurrent disease, based on clinical findings or rise in carcinoembryonic antigen (CEA).
A meta-analysis was undertaken. PubMed and Embase were searched for studies on the accuracy of whole-body imaging for patients with suspected local and/or distant recurrence of their CRC. Additionally, studies had to have included at least 20 patients with CRC and 2 × 2 contingency tables had to be provided or derivable. Articles evaluating only local recurrence or liver metastasis were excluded. Summary receiver-operating characteristic (ROC) curves were constructed from the data on sensitivity and specificity of individual studies and pooled estimates of diagnostic odds ratios (DORs) and areas under the ROC curve (AUCs) were calculated. To test for heterogeneity the Cochran Q test was used.
Fourteen observational studies were included which evaluated PET, PET/CT, CT and/or MRI. Study results were available in 12 studies for PET, in 5 studies for CT, in 5 studies for PET/CT and in 1 study for MRI. AUCs for PET, PET/CT and CT were 0.94 (0.90–0.97), 0.94 (0.87–0.98) and 0.83 (0.72–0.90), respectively. In patient based analyses PET/CT had a higher diagnostic performance than PET with an AUC of 0.95 (0.89–0.97) for PET/CT vs 0.92 (0.86–0.96) for PET.
Both whole-body PET and PET/CT are very accurate for the detection of local and/or distant recurrent disease in CRC patients with a (high) suspicion of recurrent disease. CT has the lowest diagnostic performance. This difference is probably mainly due to the lower accuracy of CT for detection of extrahepatic metastases (including local recurrence). For clinical practice PET/CT might be the modality of choice when evaluating patients with a (high) suspicion of recurrent disease, because of its best performance in patient based analyses and confident prediction of disease status.
PMCID: PMC3126998  PMID: 21468765
Colorectal cancer; Whole-body imaging; Recurrence; Staging
6.  Diffusion-Weighted MRI for Selection of Complete Responders After Chemoradiation for Locally Advanced Rectal Cancer: A Multicenter Study 
Annals of Surgical Oncology  2011;18(8):2224-2231.
In 10–24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation.
A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings.
Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI (P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0–40% on standard MRI versus 52–64% after addition of DWI. Specificity was equally high (89–98%) for both reading sessions. Interobserver agreement improved from κ 0.2–0.32 on standard MRI to 0.51–0.55 after addition of DWI.
Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation.
PMCID: PMC3136702  PMID: 21347783
7.  Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer 
European Radiology  2011;21(6):1250-1258.
To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence.
Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images.
19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was κ0.69 for standard MRI, κ0.82 for standard MRI+DWI and κ0.84 for the fusion images.
MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy.
PMCID: PMC3088810  PMID: 21240647
MRI; Diffusion magnetic resonance imaging; Rectal neoplasms; Local neoplasm recurrence; Diagnosis
8.  Value of ADC measurements for nodal staging after chemoradiation in locally advanced rectal cancer—a per lesion validation study 
European Radiology  2010;21(2):265-273.
To evaluate the performance of diffusion-weighted MRI (DWI) in addition to T2-weighted (T2W) MRI for nodal restaging after chemoradiation in rectal cancer.
Thirty patients underwent chemoradiation followed by MRI (1.5 T) and surgery. Imaging consisted of T2W-MRI and DWI (b0, 500, 1000). On T2W-MRI, nodes were scored as benign/malignant by two independent readers (R1, R2). Mean apparent diffusion coefficient (ADC) was measured for each node. Diagnostic performance was compared for T2W-MRI, ADC and T2W+ADC, using a per lesion histological validation.
ADC was higher for the malignant nodes (1.43 ± 0.38 vs 1.19 ± 0.27 *10−3 mm2/s, p < 0.001). Area under the ROC curve/sensitivity/specificity were 0.88/65%/93% (R1) and 0.95/71%/91% (R2) using T2W-MRI; 0.66/53%/82% using ADC (mean of two readers); and 0.91/56%/98% (R1) and 0.96/56%/99% (R2) using T2W+ADC. There was no significant difference between T2W-MRI and T2W+ADC. Interobserver reproducibility was good for T2W-MRI (κ0.73) and ADC (intraclass correlation coefficient 0.77).
After chemoradiation, ADC measurements may have potential for nodal characterisation, but DWI on its own is not reliable. Addition of DWI to T2W-MRI does not improve accuracy and T2W-MRI is already sufficiently accurate.
PMCID: PMC3034880  PMID: 20730540
Nodal restaging; Diffusion-weighted imaging; Apparent diffusion coefficient; MRI; Locally advanced rectal cancer

Results 1-8 (8)