Rapid On-Site Evaluation by Endosonographer of Endoscopic Ultrasound Fine-Needle Aspiration of Solid Pancreatic Lesions: A Randomized Controlled Trial.

OBJECTIVES: Rapid on-site evaluation (ROSE) by cytopathologists during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) of solid pancreatic lesions (SPLs) improves adequacy and diagnostic accuracy while reducing the number of needle passes. We evaluated the usefulness of ROSE performed by the endosonographer. METHODS: Patients with an SPL were randomly assigned to EUS-FNA with ROSE or non-ROSE. Procedure duration, number of needle passes, specimen adequacy, and adverse event rates were compared. RESULTS: Sixty-five patients were enrolled (33 in the ROSE vs 32 in the non-ROSE group). Both groups were similar in terms of age, sex, size, and location of the lesion. Specimen adequacy rates were high and similar between groups. Mean (standard deviation) procedure duration was shorter in the ROSE versus non-ROSE group (30.0 [11.3] vs 37.0 [7.2] minutes, P < 0.005), as well as the mean (standard deviation) number of needle passes (2.6 [0.8] vs 3.5 [0.8], P < 0.005). Accuracy parameters as sensitivity and accuracy of ROSE by the endosonographer for malignancy were 93% and 88%, respectively. CONCLUSIONS: After specific training, the endosonographer can accurately evaluate samples during EUS-FNA of SPL, allowing for a shorter procedure duration and a lower number of needle passes.

In Vivo Endoluminal Ultrasound Biomicroscopy and Endoscopy of Inflamed Rat Esophagus.

The development of high-frequency endoscopic ultrasound for the investigation of models of esophageal disease may offer insights for future translation to human imaging. With respect to small animal models of esophageal diseases, ultrasound imaging instrumentation must employ frequencies scaled up to maintain the compromise between image resolution and inspected region. In this sense, a 40-MHz endoluminal ultrasound biomicroscopy (eUBM) system and an endoscope were tested as diagnostic methods of imaging rat esophageal lesions in the acute and chronic phases caused by sodium hydroxide. Although endoscopy allowed grading of the esophagus in accordance with a classification specific to the epithelial alterations and including hyperemia, edema, exudates, fibrin and superficial and deep ulcerations, the eUBM images yielded the detection of superficial and deep ulcerations, as well as wall alterations caused by edema and inflammatory infiltrate in the submucosa. Additionally, eUBM enabled wall thickness measurements, which were statistically significantly increased (p < 0.05) in the acute phase.

Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial.

BACKGROUND: Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension. AIM: We evaluated the effects of simvastatin on hepatic venous pressure gradient (HVPG) and azygos vein blood flow in cirrhotic patients. METHODS: A 3-month prospective, randomized, triple-blind trial with simvastatin (40 mg/day) vs. placebo was conducted in patients with cirrhotic portal hypertension. HVPG and azygos blood flow, measured by colour Doppler endoscopic ultrasound, were assessed before and after treatment. The primary endpoint was a decrease in the HVPG of at least 20% from baseline or to ≤12 mmHg after the treatment. RESULTS: 34 patients were prospectively enrolled, and 24 completed the protocol. In the simvastatin group 6/11 patients (55%) presented a clinically relevant decrease in the HVPG; no decrease was observed in the placebo group (p=0.036). Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin. HVPG and azygos blood flow values were not correlated. No significant adverse events occurred. CONCLUSION: Simvastatin lowers portal pressure and may even improve liver function. The haemodynamic effect appears to be more evident in patients with severe portal hypertension.

Simultaneous follow-up of mouse colon lesions by colonoscopy and endoluminal ultrasound biomicroscopy.

AIM: To evaluate the potential use of colonoscopy and endoluminal ultrasonic biomicroscopy (eUBM) to track the progression of mouse colonic lesions. METHODS: Ten mice were treated with a single azoxymethane intraperitoneal injection (week 1) followed by seven days of a dextran sulfate sodium treatment in their drinking water (week 2) to induce inflammation-associated colon tumors. eUBM was performed simultaneously with colonoscopy at weeks 13, 17-20 and 21. A 3.6-F diameter 40 MHz mini-probe catheter was used for eUBM imaging. The ultrasound mini-probe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope, allowing simultaneous acquisition of colonoscopic and eUBM images. During image acquisition, the mice were anesthetized with isoflurane and kept in a supine position over a stainless steel heated surgical waterbed at 37 °C. Both eUBM and colonoscopic images were captured and stored when a lesion was detected by colonoscopy or when the eUBM image revealed a modified colon wall anatomy. During the procedure, the colon was irrigated with water that was injected through a flush port on the mini-probe catheter and that acted as the ultrasound coupling medium between the transducer and the colon wall. Once the acquisition of the last eUBM/colonoscopy section for each animal was completed, the colons were fixed, paraffin-embedded, and stained with hematoxylin and eosin. Colon images acquired at the first time-point for each mouse were compared with subsequent eUBM/colonoscopic images of the same sites obtained in the following acquisitions to evaluate lesion progression. RESULTS: All 10 mice had eUBM and colonoscopic images acquired at week 13 (the first time-point). Two animals died immediately after the first imaging acquisition and, consequently, only 8 mice were subjected to the second eUBM/colonoscopy imaging acquisition (at the second time-point). Due to the advanced stage of colonic tumorigenesis, 5 animals died after the second time-point image acquisition, and thus, only three were subjected to the third eUBM/colonoscopy imaging acquisition (the third time-point). eUBM was able to detect the four layers in healthy segments of colon: the mucosa (the first hyperechoic layer moving away from the mini-probe axis), followed by the muscularis mucosae (hypoechoic), the submucosa (the second hyperechoic layer) and the muscularis externa (the second hypoechoic layer). Hypoechoic regions between the mucosa and the muscularis externa layers represented lymphoid infiltrates, as confirmed by the corresponding histological images. Pedunculated tumors were represented by hyperechoic masses in the mucosa layer. Among the lesions that decreased in size between the first and third time-points, one of the lesions changed from a mucosal hyperplasia with ulceration at the top to a mucosal hyperplasia with lymphoid infiltrate and, finally, to small signs of mucosal hyperplasia and lymphoid infiltrate. In this case, while lesion regression and modification were observable in the eUBM images, colonoscopy was only able to detect the lesion at the first and second time-points, without the capacity to demonstrate the presence of lymphoid infiltrate. Regarding the lesions that increased in size, one of them started as a small elevation in the mucosa layer and progressed to a pedunculated tumor. In this case, while eUBM imaging revealed the lesion at the first time-point, colonoscopy was only able to detect it at the second time-point. All colonic lesions (tumors, lymphoid infiltrate and mucosal thickening) were identified by eUBM, while colonoscopy identified just 76% of them. Colonoscopy identified all of the colonic tumors but failed to diagnose lymphoid infiltrates and increased mucosal thickness and failed to differentiate lymphoid infiltrates from small adenomas. During the observation period, most of the lesions (approximately 67%) increased in size, approximately 14% remained unchanged, and 19% regressed. CONCLUSION: Combining eUBM with colonoscopy improves the diagnosis and the follow-up of mouse colonic lesions, adding transmural assessment of the bowel wall.

In vivo endoluminal ultrasound biomicroscopic imaging in a mouse model of colorectal cancer.

RATIONALE AND OBJECTIVES: The gold-standard tool for colorectal cancer detection is colonoscopy, but it provides only mucosal surface visualization. Ultrasound biomicroscopy allows a clear delineation of the epithelium and adjacent colonic layers. The aim of this study was to design a system to generate endoluminal ultrasound biomicroscopic images of the mouse colon, in vivo, in an animal model of inflammation-associated colon cancer. MATERIALS AND METHODS: Thirteen mice (Mus musculus) were used. A 40-MHz miniprobe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope. Control mice (n = 3) and mice treated with azoxymethane and dextran sulfate sodium (n = 10) were subjected to simultaneous endoluminal ultrasound biomicroscopy and white-light colonoscopy. The diagnosis obtained with endoluminal ultrasound biomicroscopy and colonoscopy was compared and confirmed by postmortem histopathology. RESULTS: Endoluminal ultrasound biomicroscopic images showed all layers of the normal colon and revealed lesions such as lymphoid hyperplasias and colon tumors. Additionally, endoluminal ultrasound biomicroscopy was able to detect two cases of mucosa layer thickening, confirmed by histology. Compared to histologic results, the sensitivities of endoluminal ultrasound biomicroscopy and colonoscopy were 0.95 and 0.83, respectively, and both methods achieved specificities of 1.0. CONCLUSIONS: Endoluminal ultrasound biomicroscopy can be used, in addition to colonoscopy, as a diagnostic method for colonic lesions. Moreover, experimental endoluminal ultrasound biomicroscopy in mouse models is feasible and might be used to further develop research on the differentiation between benign and malignant colonic diseases.

Features of in vitro ultrasound biomicroscopic imaging and colonoscopy for detection of colon tumor in mice.

The present work tested the capability of ultrasound biomicroscopy (UBM), at 45 MHz, to provide cross-sectional images with appropriate resolution and contrast to detect tumors and determine their penetration depths on the colon of mice, Mus musculus (Linnaeus 1758), treated with carcinogen for colon tumor induction. B-mode images were obtained, in vitro, from each animal (13 treated and 4 untreated) colon opened longitudinally and immersed in saline solution at room temperature. Prior to UBM inspection, all animals were also examined by colonoscopy. The layers of normal colon identified by UBM are: mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic) and muscularis externa (hypoechoic). UBM images of colon lesions presented structures corresponding to tumors (hyperechoic), lymphoid hyperplasia (hypoechoic) and polypoid tumors (hyperechoic). Additionally, tumoral lesion invasion through the colon was also identified. When compared with histopathologic analysis, all colon lesions detected by UBM were confirmed, while colonoscopic findings had two false negatives.

Validation of endoscopic ultrasound measured flow rate in the azygos vein using a flow phantom.

Increase in flow rate within the azygos vein may be used as an indicator of the degree of liver cirrhosis. The aim of this study was to evaluate the error in measurement of flow rate using a commercial endoscopic ultrasound system, using a flow phantom that mimicked azygos vein depth, diameter and flow rate. Diameter was underestimated in all cases, with an average underestimation of 0.09 cm. Maximum velocity was overestimated, by 4 ± 4% at 50°, 11 ± 3% at 60° and 23 ± 7% at 70°. The increase in error with beam-vessel angle is consistent with the error as arising from geometric spectral broadening. Flow was underestimated by amounts up to 33%, and it is noted that the overestimation caused by geometric spectral broadening is in part compensated by underestimation of diameter. It was concluded that measurement of flow rate using a commercially available endoscopic ultrasound system is dependent on the beam-vessel angle, with errors up to 33% for typical vessel depths, diameter and beam-vessel angle.

In vitro ultrasound biomicroscopic imaging of colitis in rats.

OBJECTIVE: The purpose of this study was to show the feasibility of 50-MHz ultrasound biomicroscopy (UBM) to image the rat colon. METHODS: B-mode images were obtained from ex vivo colon samples (n = 4) collected from Rattus norvegicus (Berkenhout, 1769) rats, with 2,4,6-trinitrobenzene sulfonic acid-induced colitis in 3 of them. Left colon rectangular fragments (5 x 5 mm) were obtained after necropsy, and UBM images were acquired with the samples immersed in saline at 37 degrees C. All layers of the normal intestinal wall were analyzed according to their thickness and the presence of uneven bowel mucosa (ulcers). The folds and layers detected by UBM were correlated with histopathologic analysis. RESULTS: The 4 layers of the normal colon were identified on the UBM images: the mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic), and muscularis externa (hypoechoic). On 2 UBM images, superficial ulcers were detected, approximately 0.5 mm in size, with intestinal involvement limited to the mucosa. The histopathologic analysis verified enlargement of submucosa layers due to an edema associated with sub-mucosa leukocyte infiltration. On 1 UBM image, it was possible to detect a deep ulcer, which was confirmed by the light microscopic analysis. CONCLUSIONS: An ultrasound imaging system was scaled and optimized to visualize the rat colon. Ultrasound biomicroscopy provided axial and lateral resolutions close to 25 and 45 mum, respectively, and adequate penetration depth to visualize the whole thickness of an inflamed colon. The system identified the colon layers and was able to detect mural changes and superficial ulcers on the order of 500 mum.

NOTES: transvaginal for cancer diagnostic staging: preliminary clinical application.

Laparoscopy is now a reliable method for staging gastrointestinal cancer, orienting the therapy, and avoiding unnecessary laparotomy. Natural orifice transluminal endoscopic surgery (NOTES) is an emerging concept with potential advantages for patient recovery. The first case of clinical diagnostic application of transvaginal NOTES for diagnostic cancer staging is presented. Informed consent and Institutional Commission approval were obtained for transvaginal clinical trials. On February 28, 2007, a patient with elective surgical indication for diagnostic cancer staging was submitted to transvaginal NOTES procedure, and intra- and postoperative parameters were documented. In a 50-year-old female patient presenting with ascitis, diffuse abdominal pain, and weight loss for 2 months, diagnosis of peritoneal carcinomatosis was suspected, which was also found when a CT scan was performed. Transvaginal NOTES was used for diagnostic staging of the patient, using a colonoscope introduced into the abdomen through a small incision in the vagina. Biopsies of liver, diaphragm, ovaries, and peritoneum were successfully performed. Operative time was 105 min, vaginal access and closure was obtained in 15 min. Abdominal inventory was reliable, and all 16 biopsies taken were positive for ovarian adenocarcinoma. The patient was dismissed 48 hours after the procedure without complications. Recent literature and experience of the study group suggest possibilities for preliminary clinical applications by transvaginal natural orifice surgery for diagnostic purposes.