Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is by definition a highly heterogeneous tumour, which significantly impacts its diagnosis. The aim of the study was to evaluate the diagnostic performance of imaging using computed tomography and/or magnetic resonance (MR) and biopsy for the diagnosis of cHCC-CCA. METHODS: cHCC-CCA resected between December 2006 and April 2017 with available pre-operative imaging and tumour biopsy were retrospectively included. cHCC-CCA diagnosis was based on morphological and immunophenotypical features. A total of 21 cHCC-CCA were compared to 21 intrahepatic cholangiocarcinoma (iCCA) as controls. All biopsies were reviewed. Two radiologists reviewed the cases and classified tumours into four patterns (type 1 [progressive enhancement of the entire lesion, iCCA type], type 2 [arterial enhancement with washout, HCC type], type 3 [mixed pattern with combinations of 1, 2 and 4] and type 4 [atypical pattern, areas of arterial enhancement without washout and/or hypovascular]). RESULTS: The presence of a type 3 pattern at imaging had a 48% sensitivity and 81% specificity for cHCC-CCA diagnosis. The initial diagnosis performed on biopsy was cHCC-CCA in 8/21 patients (38%). After reviewing and including immunophenotypical markers, two more cases were diagnosed as cHCC-CCA (48% sensibility, 100% specificity). When either imaging or biopsy suggested the diagnosis of cHCC-CCA, the sensitivity and specificity were 60% and 82% respectively. CONCLUSIONS: We showed that a two-step strategy combining imaging as the first step and biopsy as the second step improved the diagnostic performance of cHCC-CCA.

Texture analysis versus conventional MRI prognostic factors in predicting tumor response to neoadjuvant chemotherapy in patients with locally advanced cancer of the uterine cervix.

INTRODUCTION: To determine the performance of texture analysis and conventional MRI parameters in predicting tumoral response to neoadjuvant chemotherapy and to assess whether a relationship exists between texture tissue heterogeneity and histological type of uterine cervix cancer. METHOD AND MATERIALS: Twenty-eight patients with local advanced cervical cancer (FIGO IB2-IIIB), underwent MRI before chemotherapy. Texture analysis parameters were quantified on T2-weighted sequences, as well as the maximum diameter expressed in mm. ADC values were obtained on the ADC map. Statistical analysis included unpaired t test and ROC curve. RESULTS: No statistical correlation was found between conventional parameters and response to NACT. Mean and skewness showed a strong correlation with the histological type: Adenocarcinomas presented higher mean and skewness values (69.8 ± 10.5 and 0.55 ± 0.19) in comparison with squamous cell carcinomas. Using a cutoff value ≥ 29 for mean it was possible to differentiate the two histological types with a sensitivity of 100% and a specificity of 81%. Kurtosis showed a positive correlation with tumor response to NACT resulting higher in responders (v.m. 5.7 ± 1.1) in comparison with non-responders (2.3 ± 0.5). The optimal Kurtosis cutoff value for the identification of non-responders tumors was ≤ 3.7 with a sensitivity of 92% and a specificity of 75%. CONCLUSION: Texture analysis applied to T2-weighted images of uterine cervical cancer exceeded the role of conventional prognostic factors in predicting tumoral response; moreover, they showed a potential role to differentiate histological tumor types.

Dynamic contrast-enhanced magnetic resonance imaging in locally advanced rectal cancer: role of perfusion parameters in the assessment of response to treatment.

PURPOSE: To correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to tumor grading and to assess their reliability in predicting pathological complete response (pCR) before neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Forty patients (24 male; mean age, 67.3 ± 8.1 years) with histologically proven LARC who had undergone 3-Tesla DCE-MRI before (MRI_1) and after CRT (MRI_2) between August 2015 and February 2016 were included in this retrospective study. DCE-MRI parameters at MRI_1 and MRI_2 were extracted by two board certified radiologists in consensus reading with Olea Sphere 2.3 software using the extended Tofts model. Based on DCE-MRI results, patients were divided in complete responders (CR) and non-complete responders (nCR) and the perfusion parameters were correlated to tumor grading and pCR. RESULTS: Wash-out and Kep at MRI_1 showed significant correlation with LARC grading (P = 0.004 and 0.01, respectively). Ve showed a significant increase between MRI_1 (0.47 ± 0.27) and MRI_2 (0.63 ± 0.23; P = 0.007). Ktrans measured at MRI_1 was significantly higher in CR (0.66 ± 0.48) compared to nCR (0.53 ± 0.34, P = 0.02). CONCLUSION: Wash-out and Kep measured before CRT correlate with LARC grading. Ve changes during CRT, while Ktrans measured before CRT may predict the response to therapy. Therefore, DCE-MRI parameters can predict tumor aggressiveness and CRT efficacy, playing a role as imaging biomarkers in patients with LARC.

Peritoneal and pleural fluids may appear hyperintense on hepatobiliary phase using hepatobiliary MR contrast agents.

AIM: To describe the effect of hepatobiliary-specific MR imaging contrast agent (HBCA) administration on the signal intensity of peritoneal and pleural fluid effusions on T1-weighted MR images. MATERIALS AND METHODS: From October 2015 to May 2016 139 patients (mean 60±10 years old, 69 % males) with peritoneal or pleural effusions without biliary leakage who underwent HBCA-MRI (Gd-BOPTA or Gd-EOB-DTPA) at 1.5T and 3T were included from two centres. The fluid signal intensity was classified as hypo/iso/hyperintense before/after HBCA administration. The relative signal enhancement (RE) was calculated. RESULTS: On hepatobiliary phase (HBP), peritoneal fluids appeared hyper/isointense in 88-100 % and pleural effusions in 100 % of the patients following Gd-BOPTA administration. All fluids remained hypointense following Gd-EOB-DTPA. The signal intensity of fluids increased with both HBCA but RE was significantly higher following Gd-BOPTA (p=0.002 to <0.001). RE was correlated with HBP acquisition time-point (r=0.42, p<0.001 and r=0.50, p=0.033 for peritoneal and pleural fluids). CONCLUSION: The signal intensity of pleural and peritoneal fluids progressively increases following HBCA administration in the absence of biliary leakage. Due to its later hepatobiliary phase, this is more pronounced after Gd-BOPTA injection, leading to fluid hyperintensity that is not observed after Gd-EOB-DTPA injection. KEY POINTS: • Fluids appear hyper/isointense on HBP in most patients after Gd-BOPTA injection. • Fluids remain hypointense on HBP after Gd-EOB-DTPA injection. • RE of fluids increases with time after liver-specific Gd injection. • RE of fluids is higher in patients with chronic liver disease.

Haralick's texture features for the prediction of response to therapy in colorectal cancer: a preliminary study.

PURPOSE: Haralick features Texture analysis is a recent oncologic imaging biomarker used to assess quantitatively the heterogeneity within a tumor. The aim of this study is to evaluate which Haralick's features are the most feasible in predicting tumor response to neoadjuvant chemoradiotherapy (CRT) in colorectal cancer. MATERIALS AND METHODS: After MRI and histological assessment, eight patients were enrolled and divided into two groups based on response to neoadjuvant CRT in complete responders (CR) and non-responders (NR). Oblique Axial T2-weighted MRI sequences before CRT were analyzed by two radiologists in consensus drawing a ROI around the tumor. 14 over 192 Haralick's features were extrapolated from normalized gray-level co-occurrence matrix in four different directions. A dedicated statistical analysis was performed to evaluate distribution of the extracted Haralick's features computing mean and standard deviation. RESULTS: Pretreatment MRI examination showed significant value (p < 0.05) of 5 over 14 computed Haralick texture. In particular, the significant features are the following: concerning energy, contrast, correlation, entropy and inverse difference moment. CONCLUSIONS: Five Haralick's features showed significant relevance in the prediction of response to therapy in colorectal cancer and might be used as additional imaging biomarker in the oncologic management of colorectal patients.

Prevalence and distribution of colonic diverticula assessed with CT colonography (CTC).

OBJECTIVES: This study aimed to evaluate the prevalence of colonic diverticula according to age, gender, distribution, disease extension and symptoms with CT colonography (CTC). METHODS: The study population included 1091 consecutive patients who underwent CTC. Patients with diverticula were retrospectively stratified according to age, gender, clinical symptoms and colonic segment involvement. Extension of colonic diverticula was evaluated using a three-point quantitative scale. Using this data, a multivariate regression analysis was applied to investigate the existence of any correlation among variables. RESULTS: Colonic diverticula were observed in 561 patients (240 men, mean age 68 ± 12 years). Symptomatic uncomplicated diverticular disease (SUDD) was present in 47.4% of cases. In 25.6% of patients ≤40 years, at least one diverticulum in the colon was observed. Prevalence of right-sided diverticula in patients >60 years was 14.2% in caecum and 18.5% in ascending colon. No significant difference was found between symptomatic and asymptomatic patients regarding diverticula prevalence and extension. No correlation was present between diverticula extension and symptoms. CONCLUSION: The incidence of colonic diverticula appears to be greater than expected. Right colon diverticula do not appear to be an uncommon finding, with their prevalence increasing with patient age. SUDD does not seem to be related to diverticula distribution and extension. KEY POINTS: Incidence of colonic diverticula appears to be greater than expected. Right colon diverticula do not appear to be an uncommon finding. SUDD does not seem to be related to diverticula distribution and extension.

Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial.

OBJECTIVE: In case of incomplete colonoscopy, several radiologic methods have traditionally been used, but more recently, capsule endoscopy was also shown to be accurate. Aim of this study was to compare colon capsule endoscopy (CCE) and CT colonography (CTC) in a prospective cohort of patients with incomplete colonoscopy. DESIGN: Consecutive patients with a previous incomplete colonoscopy underwent CCE and CTC followed by colonoscopy in case of positive findings on either test (polyps/mass lesions ≥6 mm). Clinical follow-up was performed in the other cases to rule out missed cancer. CTC was performed after colon capsule excretion or 10-12 h postingestion. Since the gold standard colonoscopy was performed only in positive cases, diagnostic yield and positive predictive values of CCE and CTC were used as study end-points. RESULTS: 100 patients were enrolled. CCE and CTC were able to achieve complete colonic evaluation in 98% of cases. In a per-patient analysis for polyps ≥6 mm, CCE detected 24 patients (24.5%) and CTC 12 patients (12.2%). The relative sensitivity of CCE compared to CTC was 2.0 (95% CI 1.34 to 2.98), indicating a significant increase in sensitivity for lesions ≥6 mm. Of larger polyps (≥10 mm), these values were 5.1% for CCE and 3.1% for CTC (relative sensitivity: 1.67 (95% CI 0.69 to 4.00)). Positive predictive values for polyps ≥6 mm and ≥10 mm were 96% and 85.7%, and 83.3% and 100% for CCE and CTC, respectively. No missed cancer occurred at clinical follow-up of a mean of 20 months. CONCLUSIONS: CCE and CTC were of comparable efficacy in completing colon evaluation after incomplete colonoscopy; the overall diagnostic yield of colon capsule was superior to CTC. TRIAL REGISTRATION NUMBER: NCT01525940.

Magnetic Resonance of Rectal Cancer Response to Therapy: An Image Quality Comparison between 3.0 and 1.5 Tesla.

PURPOSE: To evaluate signal intensity (SI) differences between 3.0 T and 1.5 T on T2-weighted (T2w), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) in rectal cancer pre-, during, and postneoadjuvant chemoradiotherapy (CRT). MATERIALS AND METHODS: 22 patients with locally advanced rectal cancer were prospectively enrolled. All patients underwent T2w, DWI, and ADC pre-, during, and post-CRT on both 3.0 T MRI and 1.5 T MRI. A radiologist drew regions of interest (ROIs) of the tumor and obturator internus muscle on the selected slice to evaluate SI and relative SI (rSI). Additionally, a subanalysis evaluating the SI before and after-CRT (∆SI pre-post) in complete responder patients (CR) and nonresponder patients (NR) on T2w, DWI, and ADC was performed. RESULTS: Significant differences were observed for T2w and DWI on 3.0 T MRI compared to 1.5 T MRI pre-, during, and post-CRT (all P < 0.001), whereas no significant differences were reported for ADC among all controls (all P > 0.05). rSI showed no significant differences in all the examinations for all sequences (all P > 0.05). ∆SI showed significant differences between 3.0 T and 1.5 T MRI for DWI-∆SI in CR and NR (188.39 ± 166.90 vs. 30.45 ± 21.73 and 169.70 ± 121.87 vs. 22.00 ± 31.29, respectively, all P 0.02) and ADC-∆SI for CR (-0.58 ± 0.27 vs. -0.21 ± 0.24P value 0.02), while no significant differences were observed for ADC-∆SI in NR and both CR and NR for T2w-∆SI. CONCLUSION: T2w-SI and DWI-SI showed significant differences for 3.0 T compared to 1.5 T in all three controls, while ADCSI showed no significant differences in all three controls on both field strengths. rSI was comparable for 3.0 T and 1.5 T MRI in rectal cancer patients; therefore, rectal cancer patients can be assessed both at 3.0 T MRI and 1.5 T MRI. However, a significant DWI-∆SI and ADC-∆SI on 3.0 T in CR might be interpreted as a better visual assessment in discriminating response to therapy compared to 1.5 T. Further investigations should be performed to confirm future possible clinical application.

Magnetic resonance tumor regression grade (MR-TRG) to assess pathological complete response following neoadjuvant radiochemotherapy in locally advanced rectal cancer.

This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for quantitative assessment of the percentage of fibrosis developed within locally advanced rectal cancers (LARC) after neoadjuvant radiochemotherapy (RCT). A total of 65 patients were enrolled in the study and MR studies were performed on 3.0 Tesla scanner; patients were followed-up for 30 months. The percentage of fibrosis was quantified on T2-weighted images, using automatic K-Means clustering algorithm. According to the percentage of fibrosis, an optimal cut-off point for separating patients into favorable and unfavorable pathologic response groups was identified by ROC analysis and tumor regression grade (MR-TRG) classes were determined and compared to histopathologic TRG. An optimal cut-off point of 81% of fibrosis was identified to differentiate between favorable and unfavorable pathologic response groups resulting in a sensitivity of 78.26% and a specificity of 97.62% for the identification of complete responders (CRs). Interobserver agreement was good (0.85). The agreement between P-TRG and MR-TRG was excellent (0.923). Significant differences in terms of overall survival (OS) and disease free survival (DFS) were found between favorable and unfavorable pathologic response groups. The automatic quantification of fibrosis determined by MR is feasible and reproducible.

Performance of diffusion-weighted imaging, perfusion imaging, and texture analysis in predicting tumoral response to neoadjuvant chemoradiotherapy in rectal cancer patients studied with 3T MR: initial experience.

PURPOSE: To determine the performance of texture analysis (TA), diffusion-weighted imaging, and perfusion MR (pMRI) in predicting tumoral response in patients treated with neoadjuvant chemoradiotherapy (CRT). METHODS: 12 consecutive patients (8 females, 4 males, 63.2 ± 13.4 years) with rectal cancer were prospectively enrolled, and underwent pre-treatment 3T MRI. Treatment protocol consisted of neoadjuvant CRT with oxaliplatin and 5-fluorouracile. Unenhanced T2-weighted images TA (kurtosis), apparent diffusion coefficient (ADC), and pMRI parameters (Ktrans, Kep, Ve, IAUGC) were quantified by manually delineating a region of interest around the tumor outline. After CRT, all patients underwent complete surgical resection and the surgical specimen served as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory power of each quantitative parameter to predict complete response. RESULTS: Pathological complete response (pCR) was reported in six patients and partial response (PR) in three patients. Three patients were classified as non-responders (NR). Pre-treatment kurtosis was significantly lower in the pCR sub-group in comparison with PR + NR (p = .01). Among ADC and pMRI parameters, only Ve was significantly lower in the pCR sub-group compared with PR + NR (p = .01). A significant negative correlation between kurtosis and ADC (r = -0.650, p = .022) was observed. Pre-treatment area under the ROC curves (AUC), to discriminate between pCR and PR + NR, was significantly higher for kurtosis (0.861, p = .001) and Ve (0.861, p = .003) compared to all other parameters. The optimal cutoff value for pre-treatment kurtosis and Ve was ≤0.19 (100% sensitivity, 67% specificity) and ≤0.311 (83% sensitivity, 83% specificity), respectively. CONCLUSION: Pre-treatment kurtosis derived from T2w images and Ve from pMRI have the potential to act as imaging biomarkers of rectal cancer response to neoadjuvant CRT.

Texture analysis as imaging biomarker of tumoral response to neoadjuvant chemoradiotherapy in rectal cancer patients studied with 3-T magnetic resonance.

OBJECTIVE: The aim of this study was to determine whether texture features of rectal cancer on T2-weighted (T2w) magnetic resonance images can predict tumoral response in patients treated with neoadjuvant chemoradiotherapy (CRT). MATERIALS AND METHODS: We prospectively enrolled 15 consecutive patients (6 women, 63.2 ± 13.4 years) with rectal cancer, who underwent pretreatment and midtreatment 3-T magnetic resonance imaging. Treatment protocol consisted of neoadjuvant CRT with oxaliplatin and 5-fluorouracile. Texture analysis using a filtration-histogram technique was performed using a commercial research software algorithm (TexRAD Ltd, Somerset, England, United Kingdom) on unenhanced axial T2w images by manually delineating a region of interest around the tumor outline for the largest cross-sectional area. The technique selectively filters and extracts textures at different anatomic scales followed by quantification of the histogram using kurtosis, entropy, skewness, and mean value of positive pixels. After CRT, all patients underwent complete surgical resection and the surgical specimen served as the gold standard. RESULTS: Six patients showed pathological complete response (pCR), and 4 patients, partial response (PR). Five patients were classified as nonresponders (NRs). Pretreatment medium texture-scale quantified as kurtosis was significantly lower in the pCR subgroup in comparison with the PR + NR subgroup (P = 0.01). Midtreatment kurtosis without filtration was significantly higher in pCR in comparison with PR + NR (P = 0.045). The change in kurtosis between midtreatment and pretreatment images was significantly lower in the PR + NR subgroup compared with the pCR subgroup (P = 0.038). Pretreatment area under the receiver operating characteristic curves, to discriminate between pCR and PR + NR, was significantly higher for kurtosis (0.907, P < 0.001) compared with all other parameters. The optimal cutoff value for pretreatment kurtosis was 0.19 or less. Using this value, the sensitivity and specificity for pCR prediction were 100% and 77.8%, respectively. CONCLUSION: Texture parameters derived from T2w images of rectal cancer have the potential to act as imaging biomarkers of tumoral response to neoadjuvant CRT.

Diffusion-weighted magnetic resonance application in response prediction before, during, and after neoadjuvant radiochemotherapy in primary rectal cancer carcinoma.

INTRODUCTION: Our interest was to monitor treatment response using ADC value to predict response of rectal tumour to preoperative radiochemotherapy. MATERIALS AND METHODS: Twenty-two patients were treated with long course of radiochemotherapy, followed by surgery. Patients were examined by diffusion-weighted imaging MRI at three-time points (prior, during, and after radiochemotherapy) and were classified as responders and nonresponders. RESULTS: A statistical significant correlation was found between preradiochemotherapy ADC values and during treatment ADC values, in responders (F = 21.50, P value <0.05). An increase in ADC value during treatment was predictive of at least a partial response. DISCUSSION: Response of tumour to neoadjuvant therapy cannot be easily evaluated, and such capability might be of great importance in clinical practice, because the number of irradiated and operated patients may be superior to the number of who will really benefit from this multimodal treatment. A reliable prediction of the final clinical TN stage would allow radiotherapist to adapt multidisciplinary approach to a less invasive management, sparing surgical procedure in responder patients or even allowing an early surgery in nonresponders, which would significantly reduce radiochemotherapy related toxicity. Conclusion. Early evaluation of response during neoadjuvant radiochemotherapy treatment shows great promise to predict tumour response.

Adverse events of computed tomography colonography: an Italian National Survey.

AIM: To retrospectively study the frequency and magnitude of complications associated with computed tomography (CT) colonography in clinical practice. METHODS: A questionnaire on complications of CT colonography was sent to Italian public radiology departments identified as practicing CT colonography with a reasonable level of training. The frequency of complications and possible risk factors were retrospectively determined. Responses were collated and row frequencies determined. A multivariate analysis of the factors causing adverse events was also performed. RESULTS: 40,121 examinations were performed in13 centers during the study period. No deaths were reported. Bowel perforations occurred in 0.02% (7 exams). All perforations were asymptomatic and occurred in patients undergoing manual insufflation. Five perforations (71%) occurred in procedures performed following a recent colonoscopy. There was no significant difference between perforations associated with rectal balloon (0.017%) and those that were not (0.02%). Complications related to vasovagal reaction (either with or without spasmolytic) occurred in 0.16% (63 exams). All vasovagal reactions resolved in less than 3h, without any sequelae. CONCLUSIONS: Perforation rate at CT colonography in Italy is comparable with elsewhere in the world, occurring regardless of the experience of radiology centers. Although the risk is very small, it may not be negligible when compared with the risk of diagnostic colonoscopy.