These results demonstrate that acute clozapine exposure affects SREBP-regulated lipid biosynthesis as well as other lipid homeostasis pathways. We suggest that such drug-induced effects on lipid metabolism in peripheral tissues are relevant for the metabolic adverse effects associated with clozapine and possibly other APDs.

PURPOSE: Real-time elastography (RTE) is an ultrasound-based method for the visualization of relative strain distribution in soft tissues. Strain ratio is a semi-quantitative measurement of strain differences between two user-defined areas in an elastogram. The aim of this study was to evaluate the impact of the size and location of a reference area when measuring the strain ratio of focal lesions in a tissue-mimicking phantom and in normal liver tissue. We also investigated whether the strain ratio was affected by changing the scanner parameter: elasticity dynamic range (E-dyn). MATERIALS AND METHODS: Two investigators individually collected data by scanning 4 spherical inclusions with different elasticity in a phantom in which the elastic modulus was known in both the lesions and the background. Subsequently, a liver scan was performed in-vivo using the same scanning protocol. Five different setups with changes in reference area position or size were tested. All eight levels of the scanner setting E-dyn were recorded for each setup and the strain ratio was measured in 3 different representative elastograms for each recording situation. RESULTS: The four inclusions had significantly different mean strain ratio levels (p < 0.01) when compared to the surrounding material. Changing the position of the reference area to a deeper position influenced the strain ratio measurements significantly for all phantom lesions and in the liver. Changing the size of the reference area, while keeping the center depth unchanged, did not influence the mean strain ratio levels significantly. The strain ratio was independent of the E-dyn parameter setting. The intra- and interobserver reliability was high when measuring the strain ratio with a free-hand technique. CONCLUSION: Strain ratio provides reproducible measurements of inclusions representing different elastic contrasts using a free-hand technique in vitro. Changes in the distance of the reference areas to the ultrasound probe, representing the stress source, seem to have a significant impact on strain ratio measurements.

Endorectal elastography can be performed as an integral part of the clinical evaluation of rectal tumours and has good patient compliance. The method is a promising modality for the discrimination between adenocarcinoma and adenoma of the rectum.

Background: Rectal tumor treatment strategies are individually tailored based on tumor stage, and yield different rates of posttreatment morbidity, mortality, and local recurrence. Therefore, the accuracy of pretreatment staging is highly important. Here we investigated the accuracy of staging by magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) in a clinical setting. Material and methods: A total of 500 patients were examined at the rectal cancer outpatient clinic at Haukeland University Hospital between October 2014 and January 2018. This study included only cases in which the resection specimen had a histopathological staging of adenoma or early rectal cancer (pT1-pT2). Patients with previous pelvic surgery or preoperative radiotherapy were excluded. The 145 analyzed patients were preoperatively examined via biopsy (n ¼ 132), digital rectal examination (n ¼ 77), rigid rectoscopy (n ¼ 127), ERUS (n ¼ 104), real-time elastography (n ¼ 96), and MRI (n ¼ 84). Results: ERUS distinguished between adenomas and early rectal cancer with 88% accuracy (95% CI: 0.68-0.96), while MRI achieved 75% accuracy (95% CI: 0.54-0.88). ERUS tended to overstage T1 tumors as T2-T3 (16/24). MRI overstaged most adenomas to T1-T2 tumors (18/22). Neither ERUS nor MRI distinguished between T1 and T2 tumors. Conclusions: In a clinical setting, ERUS differentiated between benign and malignant tumors with high accuracy. The present findings support previous reports that ERUS and MRI have low accuracy for T-staging of early rectal cancer. We recommend that MRI be routinely combined with ERUS for the clinical examination of rectal tumors, since MRI consistently overstaged adenomas as cancer. In adenomas, MRI had no additional benefit for preoperative staging.

This article represents part 3 of the EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound (GIUS). It provides an overview of the examination techniques recommended by experts in the field of endorectal/endoanal ultrasound (ERUS/EAUS), as well as perineal ultrasound (PNUS). The most important indications are rectal tumors and inflammatory diseases like fistula and abscesses in patients with or without inflammatory bowel disease (IBD). PNUS sometimes is more flexible and convenient compared to ERUS. However, the technique of ERUS is quite well established, especially for the staging of rectal cancer. EAUS also gained ground in the evaluation of perianal diseases like fistulas, abscesses and incontinence. For the staging of perirectal tumors, the use of PNUS in addition to conventional ERUS could be recommended. For the staging of anal carcinomas, PNUS can be a good option because of the higher resolution. Both ERUS and PNUS are considered excellent guidance methods for invasive interventions, such as the drainage of fluids or targeted biopsy of tissue lesions. For abscess detection and evaluation, contrast-enhanced ultrasound (CEUS) also helps in therapy planning.

AimStrain elastography is a method for recording tissue hardness. Strain in different areas may be compared using strain ratio (SR). The aims of this study were to validate a previously proposed SR cut-off value of 1.25 for differentiating adenocarcinomas from adenomas and to compare the performance of endorectal ultrasonography (ERUS), strain elastography and MRI in the same patients.MethodA prospective evaluation of 120 consecutive patients with rectal neoplasia, using a predetermined elastography strain ratio cut-off value, was performed to differentiate adenomas from adenocarcinomas. ERUS and MRI were performed according to standard routine at Haukeland University Hospital, defining T0 as adenomas and T1–T4 as adenocarcinomas. Subsequent histopathology was used as the reference standard.ResultsHistopathological evaluation revealed 21 adenomas and 99 adenocarcinomas. Sensitivity, specificity and accuracy (with 95% CI) were as follows: ERUS: 0.96 (0.90–0.99), 0.62 (0.40–0.80) and 0.90 (0.83–0.94); elastography SR: 0.96 (0.90–0.99), 0.86 (0.66–0.96) and 0.94 (0.88–0.97); and MRI: 0.99 (0.94–1.00), 0.07 (0.00–0.31) and 0.87 (0.80–0.93).ConclusionThis study confirms that the elastography SR assessment accurately differentiates sessile adenomas from adenocarcinomas. SR assessment has a superior ability to differentiate adenomas and adenocarcinomas when compared with ERUS and MRI. MRI examination seems unable to recognize adenomas and should be interpreted with care when early-stage rectal neoplasia is suspected.

Aim Strain elastography is a novel approach to rectal tumour evaluation. The primary aim of this study was to correlate elastography to pT stages of rectal tumours and to assess the ability of the method to differentiate rectal adenomas (pT0) from early rectal cancer (pT1-2). Secondary aims were to compare elastography with endorectal ultrasonography (ERUS) and to propose a combined strain elastography and ERUS staging algorithm.Method In all, 120 consecutive patients with a suspected rectal tumour were examined in this staging study. Patients receiving surgery without neoadjuvant radiotherapy were included (n = 59). All patients were examined with ERUS and elastography. Treatment decisions were made by multidisciplinary team (MDT) assessment, without considering the strain elastography examination.Results Histopathology identified 21 adenomas, 13 pT1, 9 pT2, 15 pT3 and one pT4. Mean elastography strain ratios were predictive of T stage (P = 0.01). Differentiation of adenomas from early rectal cancer (pT1-2) had sensitivity, specificity and accuracy of 0.82, 0.86 and 0.84 for elastography and 0.82, 0.62 and 0.72 for ERUS. A combined staging algorithm was developed to identify tumours eligible for local resection. Based on MDT evaluation 32% of tumours later identified as pT0 or pT1 were treated with total mesorectal excision, even though a local excision might have sufficed. Combined ERUS and elastography evaluation would have significantly reduced this number to 9% (P = 0.008).Conclusion Elastography may improve the staging of adenomas and early rectal cancer compared with ERUS alone. Combined ERUS and elastography assessment is likely to further improve the selection of patients for local resection.Keywords Rectal cancer, early-stage rectal neoplasms, elastography, strain ratio, endorectal ultrasound What does this paper add to the literature? This paper is to our knowledge the first to demonstrate the ability of endorectal elastography to improve staging of pT0, pT1 and pT2 rectal tumours, proposing a combined ERUS and elastography approach to early rectal cancer staging.

Visual evaluation of elastography loops is highly reproducible in an offline setting with blinded observers, and correlates significantly with pT-stages. Strain elastography performs better than ERUS and might consequently improve staging.