Heidi B. Eggesbø

Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial

Objective. The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance. However, the evidence for its beneficial effects is limited, and conflicting reports have been published. The purpose of this study was to conduct a randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease. Material and methods. Forty-eight patients with biopsy-proven NAFLD were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months. A second liver biopsy was obtained in all subjects who completed the trial (n=44). Data analyses are restricted to this group (per-protocol analyses). The primary outcome was changes in histologically assessed liver steatosis. Secondary outcomes were changes in NAFLD activity (NAS)-score, liver steatosis assessed by computed tomography (CT), liver transaminases, body-weight, metabolic variables and inflammatory markers. Results. No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation. In contrast, beneficial effects of metformin were observed on changes in body-weight (p<0.001), serum levels of cholesterol (p=0.004), LDL-cholesterol (p<0.001), glucose (p=0.032) and on HbA1c (p=0.020). Conclusions. Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD. Nevertheless, the use of metformin could still be beneficial in this group as it is associated with a reduction in serum levels of lipids and glucose. (ClinicalTrials.gov number, NCT00303537)

Magnetic Resonance Imaging–Transectal Ultrasound Image-fusion Biopsies Accurately Characterize the Index Tumor: Correlation with Step-sectioned Radical Prostatectomy Specimens in 135 Patients

BACKGROUND Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. OBJECTIVE To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. INTERVENTION Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. RESULTS AND LIMITATIONS The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. CONCLUSION Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. PATIENT SUMMARY Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness.

A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy.

BACKGROUND Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). OBJECTIVE To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. DESIGN, SETTING, AND PARTICIPANTS This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. INTERVENTION In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB. RESULTS AND LIMITATIONS Detection rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86, 38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset analysis of patients with normal DRE, csPCa detection was similar between two-core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%; p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes. CONCLUSION Overall csPCa detection was similar between the MRI and control groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection. PATIENT SUMMARY Our randomized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinically significant prostate cancer.

Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone

To examine the performance of T2‐weighted (T2W) and diffusion‐weighted (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume (TV) and overall tumour burden.

CT characterization of developmental variations of the paranasal sinuses in cystic fibrosis

Purpose: To describe variations of paranasal sinus development in patients with cystic fibrosis (CF) and in non-CF patients examined for inflammatory sinonasal disease. We focused on anatomic variants that predispose to orbital and cerebral penetration during functional endoscopic sinus surgery (FESS), e.g. hypoplasia of the maxillary sinus and low ethmoid roof. Material and Methods: One hundred and sixteen CF patients (3-54 years, median 18) and 136 control patients (7-51 years, median 31) were examined with coronal CT of the paranasal sinuses. CF patients were grouped according to number of confirmed mutations: CF-2 (n=70), CF-1 (n=32), CF-0 (n=14). CT images were evaluated with respect to paranasal sinus development, pneumatization variants and bony variants. Results: Frontal sinus aplasia and maxillary, ethmoid, and sphenoid sinus hypoplasia were markedly more frequent in CF-2 than in control patients. No CF-2 patient had pneumatization variants such as Haller cells or concha bullosa. Low ethmoid roof was seen in 30% of CF-2 children, but in no control children. CF-1 and CF-0 groups had prevalences of aplasia and hypoplasia intermediate to that of CF-2 and control patients. Conclusion: Genetically verified CF patients had less developed sinuses, lacked pneumatization variants, and more often had anatomic variants that predispose to complications during FESS. Normally developed sinuses and pneumatization variants in some genetically unverified CF patients (CF-1, CF-0) suggest that these patients may be erroneously diagnosed.

CT characterization of inflammatory paranasal sinus disease in cystic fibrosis.

PURPOSE In patients with cystic fibrosis (CF) the prevalence of paranasal sinus affection approaches 100%. We hypothesized that the hyperviscous mucus reducing mucociliary clearance in CF patients could give sinonasal inflammatory patterns different from those in non-CF patients. We wanted to compare the extent and distribution of paranasal sinus disease and the inflammatory patterns in these two groups of patients. MATERIAL AND METHODS One-hundred-and-eight CF patients (3-54 years old) and 79 controls (7-51 years old) with paranasal sinus disease confirmed at coronal CT were compared. The extent of disease was noted for each sinus and summed for all sinuses. Inflammatory patterns were identified and classified into: 1) routine surgery group (sporadic, infundibular and ostiomeatal complex (OMC) patterns) and 2) complex surgery group (sinonasal polyposis and sphenoethmoid recess (SER) patterns). RESULTS CF patients had more widespread sinonasal inflammatory changes and more advanced disease for each sinus. Most CF patients displayed sinonasal polyposis and SER patterns while most controls displayed sporadic, infundibular or OMC patterns. As a result, 67% of CF patients were classified to the complex surgery group, compared to only 19% of controls. CONCLUSION The impaired mucociliary clearance in CF causes widespread inflammatory paranasal sinus disease, with inflammatory patterns more often requiring extensive surgery, with a higher risk of cerebrospinal fluid leak or bleeding, or involving areas that are more difficult to reach with the endoscope.

Predictive Value of Magnetic Resonance Imaging Determined Tumor Contact Length for Extracapsular Extension of Prostate Cancer

PURPOSE Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. MATERIALS AND METHODS We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. RESULTS Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. CONCLUSIONS Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension.

Imaging of sinonasal tumours

Abstract More than 70 benign and malignant sinonasal tumours and tumour-like conditions have been described. However, sinonasal tumours are rare, and sinonasal cancers comprise only 3% of all head and neck cancers and 1% of all malignancies, with a peak incidence in the 5th to 7th decades and with a male preponderance. The early symptoms and imaging findings of sinonasal tumours are similar to rhinosinusitis with runny and stuffy nose, lacrimation and epistaxis and therefore neglected both by the patients and doctors. When late symptoms such as anosmia, visual disturbances, cranial neuropathy (Cn II, IV, V, VI) or facial swelling appear, the patient is referred to sinonasal endoscopy or imaging. At the time of correct diagnosis more than half of the tumours have reached an advanced stage with a poor prognostic outcome. Even if imaging is performed in the early stages, a radiologist inexperienced with sinonasal anatomy and tumour features may easily interpret early signs of a malignant tumour as rhinosinusitis or a lesion that does not require follow-up. This article presents the imaging findings in some of the most common benign and malignant sinonasal tumours, and the TNM classification and staging of sinonasal carcinomas.

Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radiorecurrent prostate cancer: a prospective two-centre study

To report the oncological and functional outcomes of hemi salvage high‐intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer.

Proposal of a CT scoring system of the paranasal sinuses in diagnosing cystic fibrosis

The purpose of this study was to develop a paranasal sinus CT scoring system that could be used as a diagnostic tool to discriminate cystic fibrosis (CF) patients from control patients examined for sinonasal disease. The model should include as few and easily applicable criteria as possible, supported by statistical analyses and clinical judgement. We used data from 116 CF and 136 control patients. The CF patients were grouped according to the number of confirmed CF mutations: genetically verified (CF-2), or based on sweat testing and clinical findings alone (CF-1, CF-0). Nine paranasal sinus CT criteria, including development, pneumatisation variants and inflammatory patterns, were evaluated. The final model included three criteria: (a) frontal and (b) sphenoid sinus development, and (c) absence of three pneumatisation variants. This model discriminated CF-2 from controls with overlap of summed scores in only 8 of 206 patients. When this model was applied in the CF-1 and CF-0 groups, two populations seemed to exist. A larger group with summed scores overlapping that of the CF-2 group and a smaller group with summed scores overlapping that of the control group. We conclude that this CT scoring system may support, as well as exclude, a CF diagnosis in cases of diagnostic uncertainty.