Mônica Soldan

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.

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.

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 × 5 mm) were obtained after necropsy, and UBM images were acquired with the samples immersed in saline at 37°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 μm, 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 μm.

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.

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.

50 MHz ultrasound characterization of colitis on rats, in vitro

Ultrasound (50 MHz) was used for in vitro characterization of trinitrobenzene sulfonic acid-induced colitis on rats. Images and wave propagation parameters were obtained for colitis (n=38). Mean (plusmn2 se) results are: 1624.90(plusmn20.21) mmiddots-1 for speed of sound; 5.12(plusmn0.30) dBmiddotmm-1 for attenuation coefficient; 3.26(plusmn1.03)times10-3 (srmiddotmm)-1 for backscattering coefficient and 1.63 (plusmn0.10) for frequency dependence. Integrated backscattering coefficient (IBC), measured across the colon wall (n=4), ranges from 10-3 to 10-2 (srmiddotmm)-1, with the highest IBC values found in the submucosa layer. The result for speed of sound is similar to that of human sclera found in the literature. Results for attenuation and backscattering coefficients are in the same range of literature reports for human sclera and ciliary muscle, respectively. IBC plots allowed for ultrasound scattering quantification of the mucosa, submucosa and muscular layers for TNBS colitis.

Rastreamento do câncer de pâncreas

When it comes to the world population, the incidence of pancreatic cancer is low, with a cumulative risk of 1% throughout life, not rendering in screening recommendations by the World Health Organization1. Pancreatic cancer is the 4th leading cause of death by Cancer in the US, with the prospect of becoming the second in 20301. In Brazil it accounts for 2% of all types of neoplasias and for 4% of all cancer deaths. Although not among the top ten cancers in Brazil, it is the eighth leading cause of cancer death, since most patients are diagnosed in locally advanced or metastatic disease stages. Nevertheless, it holds the 13th position in incidence by type of cancer in the rankings made by the National Cancer Institute of the Brazilian Ministry of Health2. The pancreatic ductal adenocarcinoma (PDA) originates in the exocrine pancreas and accounts for 95% of pancreatic tumors. The risk of developing PDA throughout life is 1.49%, or one in 67, and its incidence increases with age3. Most diagnoses occur after the age of 50, with a peak incidence around 70 to 75 years, being more common in men. Other risk factors related to pancreatic cancer are smoking, chronic pancreatitis, cirrhosis, obesity, sedentary lifestyle, high fat and cholesterol diet, diabetes mellitus, occupational exposure to carcinogens, Jewish ancestry (Ashkenazi) and low socioeconomic status. The main family syndromes related to the disease are hereditary pancreatitis, hereditary non-polypoid colorectal cancer, hereditary breast and ovary cancer, familial atypical multiple melanoma, Peutz-Jeghers and ataxia-telangectasia4. PDA is a disease with high lethality, with a 5% five-year survival rate. Mortality has not changed much in spite of advances in surgical techniques in the last 80 years, after the introduction of pancreatoduodenectomy3. Surgical resection is the only potential cure for PDA, but in 80% of patients with symptoms the tumor is already unresectable at the time of diagnosis. Candidates for surgical resection survive on average 12 months, this time being reduced to 3.5 months in those not candidates for surgery3. Increased resectability requires the detection of PDA at an early stage, and the selective screening of patients at high risk for its development can be a good way to achieve this goal. Both genetic and modifiable factors contribute to the development of PDA, and the hereditary component can be identified in 10% of cases, with a specific mutation implicated in 20% of such individuals3. Through the identification and screening of patients at increased risk of PDA, the detection of precursor and early lesions (secondary prevention) would come and, as a consequence, there would be an increase in survival among patients undergoing surgical resection. In 2010, 50 specialists of different specialties from different countries gathered in a consortium to generate guidelines for PDA screening, the CAPS consortium, and this meeting drew some conclusions5: screening in the general population is not recommended, as the the disease’s cumulative risk is low (1.3%) throughout life; individuals considered to be at high risk for the development of PDA (>5% cumulative lifetime risk or relative risk increased by 5x) should be screened; the main tool used to quantify this risk is family history, the risk stratification being determined by the number of relatives affected and their relationship to the individuals under risk assessment; several genetic tests may identify familial susceptibility, but their role is limited because the genetic basis of PDA is not fully understood and additional genetic testing may be discovered in the near future. A screening program should aim to identify and treat T1N0M0 lesions with negative margins,. In Brazil it accounts for 2% of all types of neoplasias and for 4% of all cancer deaths. Although not among the top ten cancers in Brazil, it is the eighth leading cause of cancer death, since most patients are diagnosed in locally advanced or metastatic disease stages. Nevertheless, it holds the 13th position in incidence by type of cancer in the rankings made by the National Cancer Institute of the Brazilian Ministry of Health

In vivo endoluminal ultrasound biomicroscopic imaging of colon lesions in mouse models of cancer and inflammation

Colorectal cancer (CRC) is the third most common cancer in the world and the third leading cause of cancer-related mortality in United States. Most malignant tumors are cured if diagnosed and properly treated during the disease early stage. CRC risk increases in patients with inflammatory bowel disease (IBD), a chronic inflammatory condition affecting about five million people worldwide. Mice models of CRC and IBD are used to understand the pathogenic mechanisms, to establish therapeutic and preventive measures and to evaluate diagnostic tools. The development of minimally invasive tools to detect and monitor colon diseases could improve the studies in mice models for IBD and CRC. This has motivated the use endoluminal ultrasound biomicroscopy (eUBM) to image colon lesions in mice models for CRC and IBD, in vivo. An eUBM system was employed using a 40 MHz transducer attached to a microcomputer controlled front-end electronics. The transducer rotates inside a catheter and ultrasound cross-sectional colon images were obtained with the catheter inserted into the working channel of flexible bronchofiberscope. Water, injected through the catheter, was the ultrasound coupling medium. All colonic tissue layers in control mice (mucosa, muscularis mucosae, submucosa and muscularis externa) were detected by eUBM. Small adenomas and invasive adenocarcinomas were well visualized in eUBM images of CRC and IBD mouse models. All eUBM images correlated well with the post-mortem colon histology sections.

Comparative study between ultrasound biomicroscopy and histopathology of diversion colitis on rats

An ultrasound biomicroscopic image system, using a 50 MHz PVDF transducer (f-number = 1.5, focal distance = 4.4 mm, -6 dB bandwidth of 31.2 MHz), was employed as a complementary method to improve the diagnosis and to characterize the course and severity of diversion colitis. Nine SPF Wistar rats, Rattus norvegicus (Berkenhout, 1769), were randomly distributed into groups I- Control, II and III-Hartmanns colostomy. Tissue samples comprised the distal colon (n=3) for group I and the excluded segment excised 8 weeks in group II (n=3) and 25 weeks in group III (n=3), after colostomy. UBM images of each sample, in rectangular fragments of 5times5 mm, were obtained. Mucosa, lamina propria, submucosa and muscular layers were identified in the UBM images and morphologically correlated with the histology of the samples from group I. UMB images from group II revealed morphologically preserved muscle layer and enlarged lamina propria and submucosa (due to an edema associated with leukocyte infiltration of the lamina propria). Extensive mucosa atrophy was found in group III. The morphological results found in ultrasound images for groups I, II and III are similar to those obtained by histological examinations.