Søren Rafael Rafaelsen

Diagnostic Accuracy of Capsule Endoscopy for Small Bowel Crohn's Disease Is Superior to That of MR Enterography or CT Enterography.

BACKGROUND & AIMS Capsule endoscopy (CE) detects small bowel Crohns disease with greater diagnostic yield than radiologic procedures, although there are concerns that CE has low specificity. We compared the sensitivity and specificity of CE, magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) in patients with suspected or newly diagnosed Crohns disease. METHODS We performed a prospective, blinded study of 93 patients scheduled to undergo ileocolonoscopy, MRE, and CTE and subsequently CE if stenosis was excluded. Physicians reporting CE, MRE, and CTE results were blinded to patient histories and findings from ileocolonoscopy and other small bowel examinations. Results were compared with those from ileoscopy (n = 70), ileoscopy and surgery (n = 4), or surgery (n = 1). RESULTS Twenty-one patients had Crohns disease in the terminal ileum. The sensitivity and specificity for diagnosis of Crohns disease of the terminal ileum were 100% and 91% by CE, 81% and 86% by MRE, and 76% and 85% by CTE, respectively. Proximal Crohns disease was detected in 18 patients by using CE, compared with 2 and 6 patients by using MRE or CTE, respectively (P < .05). Small bowel stenosis was observed in 5 patients by using CTE and 1 patient by using MRE. Cross-sectional imaging results indicated additional stenoses in only 2 of the patients who received complete ileocolonoscopies. CONCLUSIONS In suspected or newly diagnosed Crohns disease, MRE and CTE have comparable sensitivities and specificities. In patients without endoscopic or clinical suspicion of stenosis, CE should be the first line modality for detection of small bowel Crohns disease beyond the reach of the colonoscope.

High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study

BACKGROUND Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints. FINDINGS Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3-31·0). Local recurrence in the observation group at 1 year was 15·5% (95% CI 3·3-26·3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths. INTERPRETATION High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer. FUNDING CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research.

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

PURPOSE Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. METHODS AND MATERIALS The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of ≤5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m2 and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). RESULTS The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). CONCLUSIONS This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.

Interobserver and intermodality agreement for detection of small bowel Crohn's disease with MR enterography and CT enterography.

Background: Magnetic resonance enterography (MRE) and computed tomography enterography (CTE) visualizes small bowel Crohns disease (CD) and its complications with high accuracy. The aim of this study was to determine the interobserver and intermodality agreement for detection of small bowel CD. Methods: Fifty patients with suspected or known CD were included in the study and all patients underwent MRE and CTE on the same day. Four radiologists with experience in MRE and CTE techniques participated. Observers were blind to patient histories, results of ileocolonoscopies, and other small bowel examinations. Readers assessed the image quality, the presence of small bowel CD, and seven findings consistent with CD. Results: The image quality was better with CTE than MRE (P < 0.001) but the diagnostic yields were comparable (P = 0.4). For detection of small bowel CD, the interobserver agreement was substantial in CTE (&kgr; = 0.64) and moderate in MRE (&kgr; = 0.48). The intermodality agreement was fair to substantial (&kgr; = 0.40‐0.64) for different observers. Two abscesses were detected and confirmed at subsequent surgery. One abscess was not detected with MRE and only recorded by two observers in CTE. A total of 10 fistulas were detected: three were confirmed at subsequent surgery and four were false‐positive findings. Conclusions: MRE and CTE have comparable diagnostic yields in patients with suspected or known CD. However, CTE provides better image quality and interobserver agreement. In a substantial number of patients the diagnosis of small bowel CD is observer‐ and modality‐dependent. (Inflamm Bowel Dis 2010;)

Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease

Abstract Objective. In patients, with symptomatic Crohns disease (CD), valid information about the presence or absence of small bowel disease activity and stenosis is clinically important. Such information supports decisions about medical or surgical therapy and can be obtained with MR enterography (MRE) or CT enterography (CTE). Materials and methods. A total of 50 patients with symptomatic pre-existing CD and a demand for small bowel imaging to support changes in treatment strategy were included in this prospective and blinded study. MRE and CTE were performed on the same day in alternating order and subsequently compared with the gold standard: pre-defined lesions at ileoscopy (n = 30) or surgery with (n = 12) or without (n = 3) intra-operative enteroscopy. Results. A total of 35 patients had active small bowel CD (jejunum 0, ileum 1, (neo)-terminal ileum 34) and 20 had small bowel stenosis. The sensitivity and specificity of MRE for detection of small bowel CD was 74% and 80% compared to 83% and 70% with CTE (p ≥ 0.5). MRE and CTE detected small bowel stenosis with 55% and 70% sensitivities, respectively (p = 0.3) and 92% specificities. Conclusions. MRE and CTE have comparable diagnostic accuracies for detection of small bowel CD and stenosis. In symptomatic patients with CD and high disease prevalence, positive predictive values are favorable but negative predictive values are low. Consequently, MRE and CTE can be relied upon, if a positive result is obtained whereas a negative enterography should be interpreted with caution.

Digital rectal examination and transrectal ultrasonography in staging of rectal cancer : a prospective, blind study

Staging of rectal carcinoma before surgical treatment was performed in a prospective blind study, comparing digital rectal exploration and transrectal linear ultrasonography (TRUS) with the resulting pathological examination. TRUS underestimated depth of penetration in 3 of 33 patients and overestimation resulted in 9 of 74. The figures for digital examination were 5 of 18 and 20 of 76, respectively. Penetration of the rectal wall was correctly identified in 56 of 61 patients by digital examination and in 59 of 61 by TRUS. Specimens without penetration of the rectal wall were identified in 26 of 33 patients by TRUS, but in not more than 13 of 33 by digital examination. Regional lymph node metastases were present in 19 patients; none were diagnosed by digital examination, but TRUS identified 11 of the 19. It is concluded that TRUS will result in more patients having the possibility of local surgery for cure.

A Comparative Study of Strain and Shear-Wave Elastography in an Elasticity Phantom

OBJECTIVE. The purpose of this study was to assess the diagnostic accuracy of strain and shear-wave elastography for determining targets of varying stiffness in a phantom. The effect of target diameter on elastographic assessments and the effect of depth on shear-wave velocity were also investigated. MATERIALS AND METHODS. We examined 20 targets of varying diameters (2.5-16.7 mm) and stiffnesses (8, 14, 45, and 80 kPa) with a 4-9-MHz linear-array transducer. Targets were evaluated 10 times with three different methods-shear-wave elastography, strain ratio, and strain histogram analysis-yielding 600 evaluations. AUCs were calculated for data divided between different stiffnesses. A 1.5-6-MHz curved-array transducer was used to assess the effect of depth (3.5 vs 6 cm) on shear-wave elastography in 80 scans. Mixed model analysis was performed to assess the effect of target diameter and depth. RESULTS. Strain ratio and strain histogram AUCs were higher than the shear-wave velocity AUC (p < 0.001) in data divided as 80 versus 45, 14, and 8 kPa. In data divided as 80 and 45 versus 14 and 8 kPa, the methods were equal (p = 0.959 and p = 1.000, respectively). Strain ratios were superior (p = 0.030), whereas strain histograms were not significantly better (p = 0.083) than shear-wave elastography in data divided as 80, 45, and 14 versus 8 kPa. Target diameter had an effect on all three methods (p = 0.001). Depth had an effect on shear-wave velocity (p = 0.001). CONCLUSION. The ability to discern different target stiffnesses varies between shear-wave and strain elastography. Target diameter affected all methods. Shear-wave elastography is affected by target depth.

Tumour hypoxia imaging with 18F-fluoroazomycinarabinofuranoside PET/CT in patients with locally advanced rectal cancer.

ObjectiveThe aim of this study was to investigate the feasibility of 18F-fluoroazomycinarabinofuranoside (18F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer. Materials and methodsThe study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with 18F-FAZA was performed with static 15 min images 2 h after injection of 18F-FAZA. Attenuation correction was obtained with a low-dose CT, and a contrast-enhanced CT was performed immediately after the PET scan. Results18F-FAZA uptake [mean and maximum standardized uptake value (SUVmean) and (SUVmax)] was significantly higher in rectal tumours than in both muscles (P<0.003) and normal intestinal walls (P<5×10−5). The tumour to muscle (T/M) ratios ranged from 1.19 to 3.05 with a mean of 1.97, whereas the tumour to intestinal wall (T/I) ratios had values of 1.73–5.81 with a mean of 2.83. Intense activity accumulating in the bladder produced obvious scattered activity, which spread into the surrounding tissue. Tumour volumes excluding scatter were therefore determined, in which the SUVmax and SUVmean were also significantly higher than in both muscles (P<0.004) and normal intestinal walls (P<2×10−5) and had T/M ratios of 1.19–2.72 with a mean of 1.85 and T/I ratios of 1.71–5.40 with a mean of 2.67. The individual SUVmax, SUVmean, T/M and T/I values were significantly higher in the entire tumour volume compared with the tumour volume adjusted for scatter from the urinary bladder (P<0.005), although the absolute differences were small. Conclusion18F-FAZA PET/CT is feasible for visualization of hypoxia in patients with rectal cancer, but scattered activity from the urinary bladder should be taken into consideration.

Echo pattern of lymph nodes in colorectal cancer: an in vitro study

Surgical specimens from 75 patients with colorectal cancer were examined within 15 min of removal with a 7.5 MHz linear-array transducer. The echo pattern of 139 lymph nodes was analysed to evaluate previous criteria of malignancy and to establish other possible criteria, which could be tested in vivo. The pathologist examined each node without knowledge of the sonographic finding. Malignant nodes were larger than benign nodes. Of 21 nodes less than 5 mm in diameter, 20 were benign. Round nodes were malignant more often (45/78) than ovoid nodes (6/61). A homogeneous echo pattern was associated with malignancy in 39 of 82 nodes in contrast to 12 of 57 with a heterogeneous pattern. Thirty-one nodes were ovoid as well as heterogeneous and all of these were benign. A hyperechoic centre was found in 14 nodes of which two were malignant. The highest predictive value for malignancy (59%) was obtained by combining the discriminative properties of shape, homogeneity and echogenicity.

Selection of colon cancer patients for neoadjuvant chemotherapy by preoperative CT scan.

Abstract Objective: Preoperative staging is essential to plan correct treatment of colon cancer and calls for objective, accurate methods for the introduction of neoadjuvant chemotherapy, which represents a new treatment option. Purpose: To evaluate the diagnostic accuracy of multislice computed tomography (CT) in local staging of colon cancer correlated with histopathological parameters, including criteria for adjuvant chemotherapy. Material and methods. A total of 74 included patients had preoperative CT scans and surgical resection of their colon tumors. Tumor stage (T-stage), extramural tumor invasion (ETI), nodal stage (N-stage), extramural venous invasion (EVI) and the distance from tumor to nearest retroperitoneal fascia (DRF) were retrospectively assessed on the CT scan and compared blindly with the results of the pathological examination, including evaluation of the criteria for adjuvant chemotherapy. Advanced tumors were defined as T3 with ETI ≥5 mm or T4. Results. Sixty-nine percent of the tumors were correctly T-staged by CT, 7% were overstaged and 24% were understaged. As to correct recognition of ETI on the CT scan, the observer was 73% accurate compared with histology (70% sensitivity (95% CI: 53–82%), 78% specificity (95% CI: 60–90%), 81% positive predictive value (PPV) (95% CI: 63–91%) and 66% negative predictive value (NPV) (95% CI: 49–80%). N-stage, EVI and DRF had poor accuracy: 53%, 53% and 64%. All patients with advanced tumors on CT fulfilled the criteria for adjuvant chemotherapy. Positive predictive value: 100% (95% CI: 88–100%). Conclusion. CT has a potential in the preoperative selection of advanced tumors suitable for neoadjuvant chemotherapy without overtreatment of low-risk patients.