Magnetic Resonance Enterography and Histology in Patients With Fibrostenotic Crohn's Disease: A Multicenter Study

INTRODUCTION Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation. METHODS This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value. RESULTS ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966). DISCUSSION MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients

Transjugular Intrahepatic Portosystemic Shunt for the Treatment of Portal Hypertension-Induced Refractory Ascites Due to Metastatic Carcinomatous Liver Disease

Three patients with a medical history of breast carcinoma and metastatic carcinomatous liver disease associated with severe portal hypertension and refractory ascites are presented. Transjugular intrahepatic portosystemic shunt creation was considered as a palliative treatment option and a valuable alternative to regular paracenteses in these patients. In 2 of the 3 patients, the refractory ascites was controlled for several months without need for paracentesis, and subsequently transjugular intrahepatic portosystemic shunt may provide valuable palliation and ascites control in patients with refractory ascites due to breast cancer-induced pseudocirrhosis.status: publishe

An Unexpected Response to Imatinib in a "Wild-Type" Gastrointestinal Stromal Tumor

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and the most frequent sarcomas in some geographic regions. In patients with metastatic GIST, the tyrosine kinase inhibitor imatinib is the first-line standard of care. Mutations in KIT or specific platelet-derived growth factor receptor alpha (PDGFRA) gene aberrations in the tumor cells predict a favorable response to this agent, while tumors without KIT or PDGFRA mutations ("wild-type" GISTs) are usually resistant to such treatment. Next-generation sequencing (NGS) is commonly used for mutational analysis of GISTs. CASE PRESENTATION: We present a case of an unexpected response to imatinib treatment in a GIST that was initially called "wild-type" based on routine NGS. A spectacular response to empirical imatinib treatment triggered further genetic analysis and led to the identification of a 45-bp duplication in KIT exon 11 undetectable by routine NGS. CONCLUSION: Negative findings on routine NGS testing for KIT alterations do not exclude the presence of actionable drug targets, as in the case of larger or complex gene insertions or deletions. Updating the NGS bioinformatics pipeline to ensure identification of larger deletions or insertions or additional Sanger sequencing is warranted in NGS driver-negative GISTs in order to allow accurate detection of actionable mutations.status: publishe

Lanreotide Reduces Liver Volume, but Might not Improve Muscle Wasting or Weight Loss, in Patients with Symptomatic Polycystic Liver Disease

Polycystic liver disease (PCLD) can induce malnutrition due to extensive hepatomegaly and patients might require liver transplantation. Six months of treatment with the somatostatin analogue lanreotide (120 mg) reduces liver volume. We investigated the efficacy of a lower dose of lanreotide and its effects on nutritional status.publisher: Elsevier articletitle: Lanreotide Reduces Liver Volume, But Might Not Improve Muscle Wasting or Weight Loss, in Patients With Symptomatic Polycystic Liver Disease journaltitle: Clinical Gastroenterology and Hepatology articlelink: http://dx.doi.org/10.1016/j.cgh.2015.05.039 content_type: article copyright: Copyright © 2015 AGA Institute. Published by Elsevier Ltd. All rights reserved.status: publishe

Lanreotide Reduces Liver Volume, But Might Not Improve Muscle Wasting or Weight Loss, in Patients With Symptomatic Polycystic Liver Disease.

BACKGROUND & AIMS: Polycystic liver disease (PCLD) can induce malnutrition owing to extensive hepatomegaly and patients might require liver transplantation. Six months of treatment with the somatostatin analogue lanreotide (120 mg) reduces liver volume. We investigated the efficacy of a lower dose of lanreotide and its effects on nutritional status. METHODS: We performed an 18-month prospective study at 2 tertiary medical centers in Belgium from January 2011 through August 2012. Fifty-nine patients with symptomatic PCLD were given lanreotide (90 mg, every 4 weeks) for 6 months. Patients with reductions in liver volume of more than 100 mL (responders, primary end point) continued to receive lanreotide (90 mg) for an additional year (18 months total). Nonresponders were offered increased doses, up to 120 mg lanreotide, until 18 months. Liver volume and body composition were measured by computed tomography at baseline and at months 6 and 18. Patients also were assessed by the PCLD-specific complaint assessment at these time points. RESULTS: Fifty-three patients completed the study; 21 patients (40%) were responders. Nineteen of the responders (90%) continued as responders until 18 months. At this time point, they had a mean reduction in absolute liver volume of 430 ± 92 mL. In nonresponders (n = 32), liver volume increased by a mean volume of 120 ± 42 mL at 6 months. However, no further increase was observed after dose escalation in the 24 patients who continued to the 18-month end point. All subjects had decreased scores on all subscales of the PCLD-specific complaint assessment, including better food intake (P = .04). Subjects did not have a mean change in subcutaneous or visceral fat mass, but did have decreases in mean body weight (2 kg) and total muscle mass (1.06 cm(2)/h(2)). Subjects also had a significant mean reduction in their level of insulin-like growth factor 1, from 19% below the age-adjusted normal range level at baseline to 50% at 18 months (P = .002). CONCLUSIONS: In a prospective study, we observed that low doses of lanreotide (90 mg every 4 weeks) reduced liver volumes and symptoms in patients with PCLD. However, patients continued to lose weight and muscle mass. The effects of somatostatin analogues on sarcopenia require investigation. Clinicaltrials.gov: NCT01315795

Diagnostic value of whole body diffusion-weighted MRI compared to computed tomography for pre-operative assessment of patients suspected for ovarian cancer

Despite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer. Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT.status: publishe

Development and validation of a polycystic liver disease-complaint-specific-assessment (POLCA)

Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SA), (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD.publisher: Elsevier articletitle: Development and validation of a polycystic liver disease complaint-specific assessment (POLCA) journaltitle: Journal of Hepatology articlelink: http://dx.doi.org/10.1016/j.jhep.2014.06.024 content_type: article copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.status: publishe

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA)

BACKGROUND & AIMS: Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SAs) and (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD. METHODS: The study population consisted of 129 patients. Items for the PCLD-complaint-specific assessment (POLCA) were developed based on the chart review of symptomatic PCLD patients (n=68) and literature, and discussed during expert-consensus-meetings. 61 patients who needed therapy were asked to complete the POLCA and the short form health survey version 2 (SF36V2) at baseline and after 6 months of SA-treatment. CT-scans were used to calculate liver volumes (LV). Factor analysis was conducted to identify subscales and remove suboptimal items. Reliability was assessed by Cronbach's alpha. Convergent, criterion validity and responsiveness were tested using prespecified hypotheses. RESULTS: In the validation group (n=61), 47 received lanreotide (LAN) and 14 were offered LAN as bridge to liver transplantation (LTx). Factor analysis identified four subscales, which correlated with the physical component summary (PCS). Baseline POLCA scores were significantly higher in LTx-listed patients. In contrast to SF36V2, POLCA-paired observations in 47 patients demonstrated that 2 subscales were lowered significantly and 2 borderline. LV reduction of ⩾ 120 ml resulted in a numerical, more pronounced relative decrease of all scores. CONCLUSIONS: In contrast to SF36V2, the POLCA shows good validity and responsiveness to measure complaint severity in PCLD

Diagnostic value of whole body diffusion-weighted MRI compared to computed tomography for pre-operative assessment of patients suspected for ovarian cancer

Despite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer. Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT. One hundred and sixty-one patients suspected for ovarian carcinoma underwent 3 T WB-DWI/MRI and contrast-enhanced CT. WB-DWI/MRI and CT were compared for confirmation of the malignant nature and primary origin of the ovarian mass, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging and prediction of incomplete resection using institutional operability criteria. Interobserver agreement between two readers was determined for WB-DWI/MRI and CT. WB-DWI/MRI showed a significantly higher accuracy than CT (93 versus 82%, p = 0.001) to confirm the malignant nature of the ovarian mass and correctly identified 26 of 32 (81%) cancers of non-ovarian origin compared to 10/32 (31%) for CT (p < 0.001). WB-DWI/MRI assigned more ovarian carcinoma patients to the correct FIGO stage (82/94, 87%) compared with CT (33/94, 35%). For prediction of incomplete resection, WB-DWI/MRI showed significantly higher sensitivity (94 versus 66%), specificity (97.7 versus 77.3%) and accuracy (95.7 versus 71.3%) compared to CT (p < 0.001). Interobserver agreement was almost perfect (κ = 0.90) for WB-DWI/MRI and moderate (κ = 0.52) for CT for prediction of incomplete resection. WB-DWI/MRI was superior to CT for primary tumour characterisation, staging and prediction of incomplete resection in patients suspected for ovarian cance

Whole-body diffusion-weighted MRI for operability assessment in patients with colorectal cancer and peritoneal metastases

BACKGROUND: Correct staging of patients with colorectal cancer is of utmost importance for the prediction of operability. Although computed tomography (CT) has a good overall performance, estimation of peritoneal cancer spread is a known weakness, a problem that cannot always be overcome by Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT); especially in infiltrative and miliary disease spread. Due to its high spatial and contrast resolution magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) might have a better performance. Our aim was to evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for prediction of peritoneal cancer spread and operability assessment in colorectal cancer patients with clinically suspected peritoneal carcinomatosis (PC). METHODS: This institutional review board approved retrospective study included sixty colorectal cancer patients who underwent WB-DWI/MRI in addition to CT for clinically suspected peritoneal metastases. WB-DWI/MRI and CT were assessed for detecting PC following the peritoneal cancer index (PCI), determination of PCI-score categorized as PC  15, detection of nodal and distant metastases and estimation of overall operability. Histopathology after surgery and biopsy and/or 6 months follow-up were used as reference standard. RESULTS: For detection of PC, CT had 43.2% sensitivity, 95.6% specificity, 84.5% positive predictive value (PPV) and 75.2% negative predictive value (NPV). WB-DWI/MRI had 97.8% sensitivity, 93.2% specificity, 88.9% PPV and 98.7% NPV. WB-DWI/MRI enabled better detection of inoperable distant metastases (all 12 patients) than CT (2/12 patients) and significantly improved prediction of PCI category [WB-DWI/MRI PCI  15: 16/17 patients (94.1%) versus CT PCI  15: 2/17 patients (11.8%); p < 0.0001)]. WB-DWI/MRI improved prediction of inoperability over CT with 90.6% sensitivity compared to 25% (p < 0.0001). CONCLUSIONS: WB-DWI/MRI significantly outperformed CT for estimation of spread of PC, overall staging and prediction of operability. Pending validation in larger prospective trials, WB-DWI/MRI could be used to guide surgical planning and minimize unnecessary exploratory laparotomies.status: publishe