Method for Acute Intravital Imaging of the Large Intestine in Live Mice.

Intravital microscopy is an imaging technique aimed at the visualization of the dynamics of biological processes in live animals. In the last decade, the development of nonlinear optical microscopy has enormously increased the use of this technique, thus addressing key biological questions in different fields such as immunology, neurobiology and tumor biology. In addition, new upcoming strategies to minimize motion artifacts due to animal respiration and heartbeat have enabled the visualization in real time of biological processes at cellular and subcellular resolution. Recently, intravital microscopy has been applied to analyze different aspect of mucosal immunity in the gut. However, the majority of these studies have been performed on the small intestine. Although crucial aspects of the biology of this organ have been unveiled, the majority of intestinal pathologies in humans occur in the large intestine.Here, we describe a method to surgically expose and stabilize the large intestine in live mice and to perform short-term (up to 2 h) intravital microscopy.

Small and Large Intestine (I): Malabsorption of Nutrients.

Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.

¿Está asociada la malrotación intestinal sintomática en el paciente adulto con el sobrecrecimiento bacteriano de intestino delgado? / Is there an association between adult symptomatic intestinal malrotation and small intestinal bacterial overgrowth?

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Near-infrared fluorescent solid material for visualizing indwelling devices implanted for medical use.

BACKGROUND: In clinical practice, various devices are implanted into the body for medical reasons. As X-ray fluoroscopy is necessary to visualize medical devices implanted into the body, the development of a less-invasive visualization method is highly desired. This study aimed to investigate the clinical applicability of our novel solid material that emits near-infrared fluorescence. METHODS: We developed a solid resin material that emits near-infrared fluorescence. This material incorporates a near-infrared fluorescent pigment, with quantum yield ≥ 20 times than that of indocyanine green. It can be sterilized for medical treatment. This resin material is designed to be molded into a catheter and inserted into the body with an endoscope clip. In this preclinical experiment using a swine model, the resin material was embedded into the body of the swine and visualized with a near-infrared fluorescence camera system. RESULTS: Endoscopic clips were placed in the mucosa of the stomach, esophagus, and large intestine, and the indwelling ureteral catheters were successfully visualized by near-infrared fluorescence laparoscopy. CONCLUSIONS: We confirmed the tissue permeability of the fluorescence emitted by our novel near-infrared fluorescent material and the possibility of its clinical application. This material may allow visualization of devices embedded in the body.

Comparison Between Small and Large Bowel Intussusception in Children: The Experience of a Large Tertiary Care Pediatric Hospital.

BACKGROUND: Intussusception is the most common cause of intestinal obstruction in young children, and delayed diagnosis may lead to serious sequelae. The objective of this study was to determine the prevalence of ileoileal intussusception and to document and compare clinical outcomes with ileocolic intussusception. METHODS: A retrospective cohort study of children with an abdominal ultrasound that diagnosed intussusception. Clinical data and diagnostic studies were retrieved, to compare ileoileal with ileocolic intussusception. RESULTS: A total of 488 patients were evaluated with an abdominal ultrasound on suspicion of intussusception; 54 (11%) had ileoileal intussusception and 30 (6%) ileocolic intussusception. The significant features distinguishing the 2 conditions were fever, more common in patients with ileoileal intussusception, and an abdominal mass, which was papable more commonly in ileocolic intussusception. None of the ileoileal intussusception patients required surgical intervention, and all were discharged without complication. CONCLUSIONS: With recent advances in abdominal ultrasound, the diagnosis of ileoileal intussusception has become easier than before. Patients presenting with small bowel intussusception may not need any immediate intervention. The presence of fever supports the diagnosis of ileoileal intussusception.

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.

Obesity is associated with risk of colorectal adenoma (CRA) and colorectal cancer. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps. We hypothesized that metformin would affect colorectal tissue S6Ser235 among obese patients with recent history of CRA. A phase IIa clinical biomarker trial was conducted via the U.S. National Cancer Institute-Chemoprevention Consortium. Nondiabetic, obese subjects (BMI ≥30) ages 35 to 80 with recent history of CRA were included. Subjects received 12 weeks of oral metformin 1,000 mg twice every day. Rectal mucosa biopsies were obtained at baseline and end-of-treatment (EOT) endoscopy. Tissue S6Ser235 and Ki-67 immunostaining were analyzed in a blinded fashion using Histo score (Hscore) analysis. Among 32 eligible subjects, the mean baseline BMI was 34.9. Comparing EOT to baseline tissue S6Ser235 by IHC, no significant differences were observed. Mean (SD) Hscore at baseline was 1.1 (0.57) and 1.1 (0.51) at EOT; median Hscore change was 0.034 (P = 0.77). Similarly, Ki-67 levels were unaffected by the intervention. The adverse events were consistent with metformin's known side-effect profile. Among obese patients with CRA, 12 weeks of oral metformin does not reduce rectal mucosa pS6 or Ki-67 levels. Further research is needed to determine what effects metformin has on the target tissue of origin as metformin continues to be pursued as a colorectal cancer chemopreventive agent.

Narrow-band imaging with magnification and the water immersion technique: a case-finding, cost-effective approach to diagnose villous atrophy.

INTRODUCTION: Narrow-band imaging with magnification endoscopy (NBI-ME) allows real-time visual assessment of the mucosal surface and vasculature of the gastrointestinal tract. This study aimed to determine the performance of NBI-ME combined with the water immersion technique (NBI-ME-WIT) in detecting villous atrophy. METHODS: All patients who underwent gastroscopy were included. The duodenum was further examined with NBI-ME-WIT only after examination with white light endoscopy did not reveal a cause of anaemia or dyspepsia. Targeted biopsies were taken of visualised areas. NBI-ME-WIT findings were compared with the final histopathological analysis. We calculated the sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of NBI-ME-WIT in detecting villous atrophy and the hypothetical cost saved by using a biopsy-avoiding approach. RESULTS: 124 patients (83 female) with a mean age of 46 (range 18-82) years were included. The most common indication for gastroscopy was abdominal pain (39%), followed by anaemia (35%), chronic diarrhoea/altered bowel habits (19%) and dyspepsia (6%). NBI-ME-WIT was able to detect all nine patients with villous atrophy - eight patchy and one total villous atrophy. The Sn, Sp, PPV and NPV of NBI-ME-WIT in detecting villous atrophy were 100.0%, 99.1%, 90.0% and 100.0%, respectively. Taking into account the cost of biopsy forceps (AUD 17) and pathology (AUD 140), this biopsy-avoidance strategy could have saved AUD 18,055 in these patients. CONCLUSION: NBI-ME-WIT is a specific and sensitive tool to recognise and accurately diagnose villous atrophy. Biopsies can be avoided in patients with normal-sized villi, which may decrease the overall cost of the procedure.

A bio-inspired self-propelling endoscopic device for inspecting the large intestine.

This article presents an inchworm-inspired, pneumatic, endoscopic device intended to navigate inside a colon. The device consists of a propulsion segment with two linear balloons and two gripper segments with four twisted balloons. The three segments can be sequentially actuated by pressurized air, which achieves a propulsive motion like an inchworm. Experimental results of the pneumatic characteristics show that the device has excellent adaptability to pipes of different diameters and good controllability of the propulsion velocity. The device is flexible enough to pass through an elbow pipe without requiring special controls, and the inspection performance of a device equipped with a camera in a flexible pipe is also presented. Moreover, the device is able to advance in an excised swine colon, which shows its great potential for applications in colonoscopy.

Spatial frequency domain imaging in 2019: principles, applications, and perspectives.

Spatial frequency domain imaging (SFDI) has witnessed very rapid growth over the last decade, owing to its unique capabilities for imaging optical properties and chromophores over a large field-of-view and in a rapid manner. We provide a comprehensive review of the principles of this imaging method as of 2019, review the modeling of light propagation in this domain, describe acquisition methods, provide an understanding of the various implementations and their practical limitations, and finally review applications that have been published in the literature. Importantly, we also introduce a group effort by several key actors in the field for the dissemination of SFDI, including publications, advice in hardware and implementations, and processing code, all freely available online.

Automated Segmentation of Colorectal Tumor in 3D MRI Using 3D Multiscale Densely Connected Convolutional Neural Network.

The main goal of this work is to automatically segment colorectal tumors in 3D T2-weighted (T2w) MRI with reasonable accuracy. For such a purpose, a novel deep learning-based algorithm suited for volumetric colorectal tumor segmentation is proposed. The proposed CNN architecture, based on densely connected neural network, contains multiscale dense interconnectivity between layers of fine and coarse scales, thus leveraging multiscale contextual information in the network to get better flow of information throughout the network. Additionally, the 3D level-set algorithm was incorporated as a postprocessing task to refine contours of the network predicted segmentation. The method was assessed on T2-weighted 3D MRI of 43 patients diagnosed with locally advanced colorectal tumor (cT3/T4). Cross validation was performed in 100 rounds by partitioning the dataset into 30 volumes for training and 13 for testing. Three performance metrics were computed to assess the similarity between predicted segmentation and the ground truth (i.e., manual segmentation by an expert radiologist/oncologist), including Dice similarity coefficient (DSC), recall rate (RR), and average surface distance (ASD). The above performance metrics were computed in terms of mean and standard deviation (mean ± standard deviation). The DSC, RR, and ASD were 0.8406 ± 0.0191, 0.8513 ± 0.0201, and 2.6407 ± 2.7975 before postprocessing, and these performance metrics became 0.8585 ± 0.0184, 0.8719 ± 0.0195, and 2.5401 ± 2.402 after postprocessing, respectively. We compared our proposed method to other existing volumetric medical image segmentation baseline methods (particularly 3D U-net and DenseVoxNet) in our segmentation tasks. The experimental results reveal that the proposed method has achieved better performance in colorectal tumor segmentation in volumetric MRI than the other baseline techniques.

Ultrasonographic evaluation of changes over time in one defecation cycle in adults with functional constipation: A report of two cases.

We described fecal retention during the defecation cycles of adults with functional constipation via ultrasonography (US) of the large intestine. US was performed continuously after the last defecation until the next defecation. We defined the fecal finding level on US as follows: weak fecal retention, a marginally high echo in the colonic lumen; or strong fecal retention, a strongly echoic colon lumen with showing a crescent-shaped acoustic shadow on transverse images and haustrations on longitudinal images. The findings confirmed weak fecal retention in the colon throughout the defecation cycle and a pattern of strong fecal retention in the descending and sigmoid colon and over the colon, including the transverse colon and ascending colon, in patients with functional constipation.

Usefulness of close observation with non-magnified blue laser imaging for determining cold polypectomy indications.

PURPOSE: To examine the usefulness of non-magnified close observation with blue laser imaging (BLI) using a colonoscope with close observation capability in determining indications for cold polypectomy. METHODS: We conducted an image evaluation study on 100 consecutive colorectal lesions of 10 mm or less which were observed endoscopically without magnification using BLI mode prior to treatment. Two experts and two non-experts reviewed the images using the Japan NBI expert team (JNET) classification and the diagnostic accuracy was analyzed. RESULTS: The final pathological diagnoses of the 100 lesions were hyperplastic/sessile serrated polyp (HP/SSP), low grade dysplasia (LGD), high grade dysplasia (HGD) and deep submucosal invasive cancer (dSM), respectively, in 12, 79, 9 and 0 lesions. When JNET classification type 1 corresponds to HP/SSP; 2A to LGD; 2B to HGD; and 3 to dSM; the overall diagnostic accuracy was 84.3%. Accuracy was 90.5% for experts and 78.0% for non-experts. High confidence rate was 67.5% for experts and 48.0% for non-experts. In diagnostic accuracy for HGD, the sensitivity, specificity, PPV and NPV were, respectively, 77.8%, 98.9%, 87.5% and 97.8% for experts; and 66.6%, 92.3%, 46.2% and 96.6% for non-experts. CONCLUSIONS: The diagnostic accuracy of unmagnified close observation with BLI using a colonoscope with close observation capability is similar to that reported for magnifying endoscopy and is useful in predicting the histological diagnosis of colorectal polyps of 10 mm or less although the effectiveness may be limited for non-experts. This modality is a potentially useful tool in deciding indications for cold polypectomy.

Clinical characteristics of lupus enteritis in Japanese patients: the large intestine-dominant type has features of intestinal pseudo-obstruction.

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4-14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.

Clinical features and outcome in horses with severe large intestinal thickening diagnosed with transabdominal ultrasonography: 25 cases (2003-2010).

OBJECTIVE To describe clinical features and outcome of horses with severe large intestinal thickening diagnosed with transabdominal ultrasonography. DESIGN: Retrospective case series. ANIMALS 25 horses. PROCEDURES Medical records of horses that underwent transabdominal ultrasonography between 2003 and 2010 were reviewed. Horses were included if the wall of the large intestine was ≥ 9 mm thick in any of 6 abdominal zones. RESULTS Median age was 13 years (range, 3 to 28 years). Horses were initially examined because of colic, diarrhea, inappetence, weight loss, lethargy, fever, or hematuria. Severe large intestinal thickening (range, 9 to 46.6 mm; mean ± SD, 18.8 ± 6.8 mm) was the primary ultrasonographic finding in all horses. Thickened large intestine was more likely to be detected in ventral versus upper (ie, combined paralumbar and intercostal) abdominal zones and in right versus left zones. Eleven horses survived and had resolution of clinical signs, including the l horse treated surgically for colon torsion. An additional horse survived but continued to have intermittent colic. Ten horses were euthanized or died, including 3 horses with neoplasia and 3 with colitis. Three horses were lost to follow-up, including 1 horse with a cecal mass and 1 with hepatosplenic lymphoma. Severity of thickening and number of zones affected were not significantly different between survivors and nonsurvivors. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in horses undergoing transabdominal ultrasonography, large intestinal wall thickness ≥ 9 mm may be detected in patients with a variety of conditions. Ultrasonographic examination of all abdominal zones was helpful to determine the extent of thickening and identify additional findings that helped prioritize differential diagnoses.