Endorectal ultrasound and magnetic resonance imaging for staging of early rectal cancers: how well does it work in practice?

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 = 132), digital rectal examination (n = 77), rigid rectoscopy (n = 127), ERUS (n = 104), real-time elastography (n = 96), and MRI (n = 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.

Imaging assessment of early rectal cancer.

Early rectal cancer (ERC) is defined as invasive adenocarcinoma spreading into, but not beyond, the submucosa or muscularis propria-that is a Dukes'A: T1N0 or T2N0 tumour in the tumour node metastasis (TNM) classification (Taylor et al. 2008). Among these tumours it is suggested that the most superficial T1 tumours least likely to metastasize to local lymph nodes than adenocarcinoma invading deeper where the rich lymphatic and venous plexuses within the submucosa provide a mechanism for tumour spread beyond the rectum. Currently, only about 10 % of patients presenting symptomatically with rectal cancer are diagnosed with early disease; however, up to 30 % of screen detected cancers are being identified as Dukes'A. Thus, the overall detection of early stage tumours is likely to increase following greater implementation in screening programs. The goal of this invited review is to provide recommendations based on the consensus discussion on the information from preoperative imaging that is of relevance for clinical decision-making for patients with early rectal cancer.

Long-term impact of gastropexy on use of acid-reducing medication, second operations for gastroesophageal reflux and subjective reflux symptoms after sleeve gastrectomy.

We investigated whether adding gastropexy to sleeve gastrectomy (SG) reduced gastroesophageal reflux disease (GERD) in patients operated for severe obesity, assessed mainly by use of anti-reflux medication (ARM) and second operations due to GERD worsening. In a prospective non-randomized study, patients undergoing SG at two Norwegian hospitals were included from 2011 to 2015 and followed for 7 years. GERD was defined by regular use of ARM, and epigastric pain and heartburn were measured by the Rome II questionnaire. Gastropexy was done by suturing the gastrocolic ligament to the staple line. Patients undergoing SG only, mainly before gastropexia was introduced in 2013, were compared to those with additional gastropexy from 2013 onwards. Of 376 included patients (75% females, mean age 42.6 years and BMI 42.9 kg/m2 ), 350 (93%) and 232 (62%) were available for evaluation after 1 and 7 years, respectively. Baseline characteristics in the no-gastropexy (n = 235) and gastropexy groups (n = 141) were similar. In patients without ARM use before surgery, the use increased and in those that used ARM at baseline, the proportion decreased, with no difference in the no-gastropexy and gastropexy groups. With a combined endpoint of ARM use and/or second operation for GERD, there was no difference during follow-up between the two groups. With time, adding gastropexy did not reduce symptoms of GERD significantly. In this population, adding gastropexy to SG did not reduce use of ARM and/or second operation for uncontrolled GERD, epigastric pain or heartburn during the first 7 postoperative years.

Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver.

BACKGROUND: Several antipsychotic drugs (APDs) have high propensity to induce weight gain and dyslipidemia in patients, with clozapine and olanzapine as the most potent drugs. These lipid-related effects have been attributed to drug-mediated blockade or antagonism of histamine H1 and serotonin 5-HT2 receptors as well as activation of hypothalamic AMP-activated protein kinase. We recently showed that APDs activate lipid biosynthesis in cultured liver cells through stimulation of the sterol regulatory element-binding protein (SREBP) transcription factors. OBJECTIVE: The objective of the study was to search for clozapine-related lipogenic effects in peripheral tissues in vivo using rat liver as target organ. MATERIALS AND METHODS: Adult female Sprague-Dawley rats were administered single intraperitoneal injections of clozapine (25 and 50 mg/kg). Hepatic lipid levels were measured during a 48-h time course. Real-time quantitative PCR was used to analyze expression of genes involved in lipid biosynthesis, oxidation, efflux, and lipolysis. RESULTS: We identified an initial up-regulation of central lipogenic SREBP target genes, followed by a marked and sustained down-regulation. We also observed a sequential transcriptional response for fatty acid beta-oxidation and cholesterol efflux genes, normally controlled by the peroxisome proliferator activated receptor alpha and liver X receptor alpha transcription factors, and also down-regulation of genes encoding major lipases. The transcriptional responses were associated with a significant accumulation of triacylglycerol, phospholipids, and cholesterol in the liver. CONCLUSION: 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.

EFSUMB Recommendations for Gastrointestinal Ultrasound Part 3: Endorectal, Endoanal and Perineal Ultrasound.

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.

Memantine attenuates the increase in striatal preproenkephalin mRNA expression and development of haloperidol-induced persistent oral dyskinesias in rats.

Tardive dyskinesia (TD) is a serious motor side effect of long-term neuroleptic treatment that may persist after drug withdrawal. Alterations in striatal enkephalinergic neurons due to excessive glutamatergic activity is a possible pathogenetic mechanism. We studied the effect of the NMDA antagonist memantine in a rat model of TD, in which vacuous chewing movements (VCM) were induced by 20 weeks of haloperidol administration. The striatal density of preproenkephalin mRNA was measured and the number of neurons estimated. Haloperidol induced persistent VCM that was associated with increased striatal expression of preproenkephalin mRNA. Memantine inhibited the development of haloperidol-induced persistent VCM and attenuated the increase in preproenkephalin mRNA expression. This suggests that glutamate-mediated up-regulation of striatal enkephalin plays a role in the development of haloperidol-induced persistent oral dyskinesias.

Combination of real-time elastography and urine prostate cancer gene 3 (PCA3) detects more than 97% of significant prostate cancers.

OBJECTIVE: The prostate cancer gene 3 (PCA3) score in urine is a promising biomarker for prostate cancer. Real-time elastography (RTE) is a well-documented ultrasound modality. The objective of this study was to evaluate the ability to detect significant cancer foci in the prostate with these methods alone and in combination. MATERIAL AND METHODS: From September 2009 to September 2010, 40 patients planned for radical prostatectomy underwent a PCA3 urine test and RTE before operation. A Hitachi EUB-8500 with prostate end-fire transrectal probe was used. The PCA3 score was evaluated with a standard cut-off value of 35. RTE was evaluated in correlation with whole-mount section pathology. Three patients fulfilled the criteria for insignificant prostate cancer and were excluded from the study. RESULTS: The PCA3 score was increased in 26 patients (70%). RTE identified at least one tumour in 33 out of 37 patients (89%). RTE detected the largest tumour in 27 out of 37 patients (73%). More than one cancer was present in 29 patients and RTE identified more than one tumour in 13 of these. The RTE was false positive in four patients. The PCA3 score was increased in three out of four false-negative RTE patients. By combining both methods, 36 out of 37 patients (97%) with significant prostate cancer were detected. CONCLUSIONS: The combination of PCA3 score and RTE detected 97% of significant prostate cancers. The combinative use of RTE and PCA3 will be further investigated in an unselected series of men with suspected prostate cancer.