Magnetic resonance cholangiography in the diagnosis of dominant strictures in pediatric-onset primary sclerosing cholangitis.

BACKGROUND: Magnetic resonance cholangiopancreaticography (MRCP) has become the primary imaging modality in primary sclerosing cholangitis (PSC). Endoscopic retrograde cholangiopancreaticography (ERCP) is recommended when a dominant stricture (DS) of bile ducts is suspected in MRCP. However, MRCP criteria for DS are lacking. AIMS: To evaluate the diagnostic accuracy of MRCP in the diagnosis of DS in patients with pediatric-onset PSC. METHODS: ERCP and MRCP images of patients with pediatric-onset PSC (n=36) were evaluated for the presence of DS applying the diameter-based ERCP criteria. The diagnostic accuracy of MRCP in detecting DS was calculated using ERCP as the gold standard. RESULTS: The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of MRCP for detecting DS were 62%, 89%, 5.6, 0.43, and 81%. Most common reasons for incongruent ERCP/MRCP assessment were (1) MRCP stenosis not fulfilling the diameter criteria of ERCP, resulting in false negative MRCP evaluation, and (2) lack of filling pressure in MRCP, resulting in false positive MRCP evaluation. CONCLUSION: The high positive likelihood ratio of MRCP in detecting DS suggests that MRCP is a useful tool in the follow-up of PSC. However, diameter limits of DS should probably be less strict in MRCP than in ERCP.

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

BACKGROUND: Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. METHODS: This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. RESULTS: Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. CONCLUSIONS: There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status. CLINICAL TRIAL REGISTRATION: NCT01531621/EudraCT2011-003158-24.

Humanin vivoliver and tumor bioimpedance measured with biopsy needle.

Objective.Liver biopsy is an essential procedure in cancer diagnostics but targeting the biopsy to the actual tumor tissue is challenging. Aim of this study was to evaluate the clinical feasibility of a novel bioimpedance biopsy needle system in liver biopsy and simultaneously to gatherin vivobioimpedance data from human liver and tumor tissues.Approach.We measured human liver and tumor impedance datain vivofrom 26 patients who underwent diagnostic ultrasound-guided liver biopsy. Our novel 18 G core biopsy needle tip forms a bipolar electrode that was used to measure bioimpedance during the biopsy in real-time with frequencies from 1 kHz to 349 kHz. The needle tip location was determined by ultrasound. Also, the sampled tissue type was determined histologically.Main results.The bioimpedance values showed substantial variation between individual cases, and liver and tumor data overlapped each other. However, Mann-Whitney U test showed that the median bioimpedance values of liver and tumor tissue are significantly (p < 0.05) different concerning the impedance magnitude at frequencies below 25 kHz and the phase angle at frequencies below 3 kHz and above 30 kHz.Significance.This study uniquely employed a real-time bioimpedance biopsy needle in clinical liver biopsies and reported the measured humanin vivoliver and tumor impedance data. Impedance is always device-dependent and therefore not directly comparable to measurements with other devices. Although the variation in tumor types prevented coherent tumor identification, our study provides preliminary evidence that tumor tissue differs from liver tissuein vivo,and this association is frequency-dependent.

Repeated centralized multidisciplinary team assessment of resectability, clinical behavior, and outcomes in 1086 Finnish metastatic colorectal cancer patients (RAXO): A nationwide prospective intervention study.

BACKGROUND: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. METHODS: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. FINDINGS: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12-0·19), 39·1 months in R2-resected/LAT (0·39; 0·29-0·53) patients, and 20·8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. INTERPRETATION: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. FUNDING: The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.

Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing.

Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial plasma samples (n = 80) from ten metastatic colorectal cancer (mCRC) patients with a known KRAS mutation in their primary tumor. The patients were undergoing oncological treatment with bevacizumab in combination with alternating capecitabine and oxaliplatin or irinotecan. Baseline ddPCR KRAS mutation allele frequency (MAF) values ranged from 0% to 63%. The first radiologic response evaluation criteria in solid tumors (RECIST) evaluation was performed 45-63 days after the initiation of treatment, and by this time three patients had an undetectable level of KRAS mutation, one had a MAF value of 0.5%, and one had a MAF value of 3% that had been reduced by 95% from the baseline value. In three of these patients the RECIST assessment was stable disease and in two partial response. In seven patients, ddPCR MAF values increased before radiological disease progression or death, while one patient remained disease-free with an undetectable KRAS mutation level. Next, we analyzed all available plasma samples with the Idylla ctKRAS system (n = 60), and found that the overall degree of agreement between ddPCR and Idylla was almost perfect (kappa value = 0.860). We used next-generation sequencing (NGS) to detect treatment-induced mutations in the last serial plasma sample of each patient, but were unable to find any new mutations when compared to the primary tumor. This study shows that ddPCR and Idylla are equally efficient for the detection of KRAS mutations in the liquid biopsies from mCRC patients and that ctDNA may indicate the disappearance of treatment responsive KRAS positive mCRC clones and serve as an early sign of disease progression.

A body-sized phantom for evaluation of diffusion-weighted MRI data using conventional, readout-segmented, and zoomed echo-planar sequences.

BACKGROUND: Abdominal diffusion-weighted imaging (DWI) has been rapidly increasing during the last few years. For the evaluation of new DWI techniques, the development of suitable phantoms and quality assurance methods is important. PURPOSE: To construct a body-diameter phantom for abdominal DWI and study the impact of different acquisition options on image quality. MATERIAL AND METHODS: A phantom with a diameter of 31 cm and a volume of 26 L was constructed, containing four samples representing a clinically relevant range of apparent diffusion coefficient (ADC) values. Measurements were carried out on 1.5T and 3.0T MRI systems using conventional echo-planar imaging (EPI), readout-segmented EPI, and zoomed EPI (3.0T) sequences. The effects of parallel imaging, coil intensity normalization, and patient-specific B1 shim (3.0T) were also examined. ADC values and signal-to-noise ratios of the samples were measured, and the level of artifacts was visually evaluated. RESULTS: The agreement of ADC values between different acquisition options was generally good, but higher values (by 0.07 × 10(-3) mm(2)/s on the average) with readout-segmented EPI as well as ADC variations of approximately 0.1 × 10(-3) mm(2)/s in slice direction were observed. The image artifacts were reduced by using patient-specific B1 shim, readout-segmented EPI, or zoomed EPI. CONCLUSION: The body-sized phantom demonstrated well the expected image artifacts in DWI with large field of view. The use of patient-specific B1 shim, readout-segmented EPI, or zoomed EPI improved image quality of DWI in this study.