Comparison of clinical utility of deep learning-based systems for small-bowel capsule endoscopy reading.

BACKGROUND AND AIM: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting. METHODS: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. RESULTS: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). CONCLUSIONS: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed.

Impact of looping on premalignant polyp detection during colonoscopy.

BACKGROUND: The presence of premalignant polyps on colonoscopy is an indicator of metachronous colorectal cancer. Looping during colonoscopy is associated with old age, female sex, and colonoscopy insertion time. However, the clinical significance of looping is not fully understood. We aimed to clarify the effect of looping on colorectal premalignant polyp detection. AIM: To assess the effects of looping on premalignant polyp detection using logistic regression analyses. METHODS: We retrospectively investigated patients who underwent colonoscopy at Toyoshima Endoscopy Clinic between May, 2017 and October, 2020. From the clinic's endoscopy database, we extracted data on patient age, sex, endoscopist-assessed looping, colonoscopy duration, endoscopist experience, detection rate, and number of premalignant polyps. RESULTS: We assessed 12259 patients (mean age, 53.6 years; men, 50.7%). Looping occurred in 54.3% of the patients. Mild and severe looping were noted in 4399 and 2253 patients, respectively. The detection rates of adenomas, advanced adenomas, high-risk adenomas, clinically significant serrated polyps (CSSPs), and sessile serrated lesions (SSLs) were 44.7%, 2.0%, 9.9%, 8.9% and 3.5%, respectively. The mean numbers of adenomas and SSLs were 0.82 and 0.04, respectively. The detection rates of adenomas, high-risk adenomas, and CSSPs increased with looping severity (all P < 0.001). The number of adenomas increased with looping severity (P < 0.001). Multivariate analyses found that detection of adenomas, high-risk adenomas, and CSSPs was associated with severe looping (P < 0.001, P < 0.001, and P = 0.007, respectively) regardless of age, sex, time required for colonoscope insertion and withdrawal, and endoscopist experience. CONCLUSION: Looping severity was independently associated with high detection rates of premalignant polyps. Therefore, looping may predict the risk of metachronous colorectal cancer. Endoscopists should carefully examine the colorectum of patients with looping.

Impairment of endothelium-dependent vasodilator function of retinal blood vessels in adult rats with a history of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease, initiated by delayed retinal vascular growth after premature birth. In the majority of cases, ROP resolves spontaneously; however, a history of ROP may increase the risk of long-term visual problems. In this study, we evaluated the endothelial function of retinal blood vessels in adult rats with a history of ROP. ROP was induced in rats by subcutaneous injection of a vascular endothelial growth factor receptor tyrosine kinase inhibitor (KRN633) on postnatal day (P) 7 and P8. On P56, vasodilator responses to acetylcholine, GSK1016790A (an activator of transient receptor potential vanilloid 4 channels), NOR3 (a nitric oxide [NO] donor), and salbutamol (a ß2-adrenoceptor agonist) were assessed. Compared to age-matched controls, retinal vasodilator responses to acetylcholine and GSK1016790A were attenuated in P56 rats with a history of ROP. No attenuation of acetylcholine-induced retinal vasodilator response was observed under inhibition of NO synthase. Retinal vasodilator responses to NOR3 and salbutamol were unaffected. These results suggest that the production of and/or release of NO is impaired in retinal blood vessels in adult rats with a history of ROP. A history of ROP might increase the risk of impaired retinal circulation in adulthood.

Priority stratification for colonoscopy based on two-sample faecal immunochemical test screening: results from a cross-sectional study at an endoscopy clinic in Japan.

OBJECTIVES: Little has been reported on the yield and characteristics of colorectal neoplasia detected by the two-sample faecal immunochemical test (FIT), particularly the difference between subjects with two-positive results on the two-sample FIT and those with one-positive results. We aimed to assess risk stratification among patients with positive two-sample FIT to prioritise colonoscopy. DESIGN: A retrospective cross-sectional study. SETTING: A single-centre, representative endoscopy clinic in Japan. PARTICIPANTS: Consecutive patients who underwent colonoscopy were enrolled. Indications for colonoscopy included two-positive results on the two-sample FIT (FIT (+/+)), one-positive results on the two-sample FIT (FIT (+/-)), and other reasons (non-FIT group, including presence of symptoms, screening or surveillance). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were detection rates of colorectal cancers, including in situ (all cancers) and invasive cancers, based on the indications for colonoscopy. Secondary outcomes were cancer features, such as location, size, T stage and histological subtype. RESULTS: Of the 8724 patients, 264 underwent colonoscopy following FIT (+/+), 1018 following FIT (+/-) and 7442 for reasons other than positive FIT. Detection rates of all (and invasive) cancers in the FIT (+/+), FIT (+/-) and non-FIT groups were 12.1% (8.3%), 1.9% (0.3%) and 0.4% (0.2%), respectively. The cancer detection rates were much higher in the FIT (+/+) group than in the FIT (+/-) group, which in turn had higher rates than the non-FIT group. Moreover, the FIT (+/+) group showed more advanced T stages on tumour, node, metastasis (TNM) classification (Tis/T1/T2/T3/T4: 10/7/4/10/1) than the FIT (+/-) group (16/1/2/0/0, p<0.001). CONCLUSIONS: Two-positive results for two-sample FIT showed a much higher yield for more advanced colorectal cancers than the one-positive result. High priority for diagnostic colonoscopy should be assigned to patients with two-positive-FIT results.

A single nucleotide polymorphism in Prostate Stem Cell Antigen is associated with endoscopic grading in Kyoto classification of gastritis.

The risk allele of a single nucleotide polymorphism (SNP) rs2294008 in the Prostate stem cell antigen (PSCA) gene is strongly associated with gastric cancer. Although the Kyoto classification score is believed to be an indicator of gastric cancer risk, it lacks supporting genetic evidence. We investigated the effect of this risk allele of PSCA SNP on the Kyoto score. Participants without a history of gastric cancer or Helicobacter pylori (H. pylori) eradication underwent esophagogastroduodenoscopy, H. pylori evaluation, and SNP genotyping. The Kyoto score is the sum of scores obtained from endoscopy-based atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The Kyoto score is novel in the light of scoring for gastritis. A total of 323 patients were enrolled (number of individuals with genotype CC: 52; CT: 140; TT: 131, average age: 50.1 years, male: 50.8%). The patient baseline characteristics including age, sex, body mass index, smoking, drinking, family history of gastric cancer, and H. pylori status had no association with PSCA SNP. The Kyoto score was higher in T (CT or TT genotype; risk allele) carriers than in CC carriers. Atrophy, enlarged folds, and diffuse redness scores were higher in T allele carriers (risk allele) than in CC genotype individuals. In multivariate analysis, the Kyoto score was independently associated with PSCA SNP (OR: 1.30, p = 0.012). Thus, the Kyoto score was associated with a genetic predisposition.

The simplified Kyoto classification score is consistent with the ABC method of classification as a grading system for endoscopic gastritis.

The ABC method combined with Helicobacter pylori antibody and serum pepsinogen is a useful predictive method for stomach cancer. Kyoto classification is a new grading system for endoscopic gastritis. However, the consistency of the Kyoto score with the ABC method remains unclear. The Kyoto classification score, which ranges from 0 to 8, is based on the following findings: atrophy, intestinal metaplasia, diffuse redness, nodularity, and enlarged folds. Furthermore, we defined a simplified Kyoto classification score as the sum of scores of just atrophy and intestinal metaplasia. The association between the Kyoto classification score and the ABC method was analyzed using the Kruskal-Wallis and Steel-Dwass tests. A total of 307 subjects were enrolled. Kyoto classification scores were similar in groups B, C, and D, while scores in group A were significantly lower than those of the other groups. The simplified Kyoto classification score showed the same stepwise increase as the classification of the ABC method. In conclusion, unlike the Kyoto classification score, the simplified Kyoto score showed the same significant stepwise increase as the classification of the ABC method.

Abnormal Vascular Phenotypes Associated with the Timing of Interruption of Retinal Vascular Development in Rats.

Pathological angiogenesis is a leading cause of blindness in several retinal diseases. The key driving factor inducing pathological angiogenesis is the pronounced hypoxia leading to a marked, increased production of vascular endothelial growth factor (VEGF). The aim of this study was to determine whether the abnormal vascular growth occurs in a manner dependent on the degree of the vascular defects. Vascular defects of two different degrees were created in the retina by subcutaneously treating neonatal rats with the VEGF receptor (VEGFR) tyrosine kinase inhibitor KRN633 on postnatal day (P) 4 and P5 (P4/5) or P7 and P8 (P7/8). The structure of the retinal vasculature changes was examined immunohistochemically. Prevention of vascular growth and regression of some preformed capillaries were observed on the next day, after completion of each treatment (i.e., P6 and P9). The vascular regrowth occurred as a result of eliminating the inhibitory effect on the VEGFR signaling pathway. KRN633 (P4/5)-treated rats exhibited a retinal vasculature with aggressive intravitreal neovascularization on P21. On the other hand, the appearance of tortuous arteries is a representative vascular pathological feature in retinas of KRN633 (P7/8)-treated groups. These results suggest that an interruption of the retinal vascular development at different time points induces different vascular pathological features in the retina. Pharmacological agents targeting the VEGF signaling pathway are useful for creating an abnormal retinal vasculature with various pathological features in order to evaluate the efficacy of anti-angiogenic compounds.

Clinical usefulness of a deep learning-based system as the first screening on small-bowel capsule endoscopy reading.

BACKGROUND AND AIM: To examine whether our convolutional neural network (CNN) system based on deep learning can reduce the reading time of endoscopists without oversight of abnormalities in the capsule-endoscopy reading process. METHODS: Twenty videos of the entire small-bowel capsule endoscopy procedure were prepared, each of which included 0-5 lesions of small-bowel mucosal breaks (erosions or ulcerations). At another institute, two reading processes were compared: (A) endoscopist-alone readings and (B) endoscopist readings after the first screening by the proposed CNN. In process B, endoscopists read only images detected by CNN. Two experts and four trainees independently read 20 videos each (10 for process A and 10 for process B). Outcomes were reading time and detection rate of mucosal breaks by endoscopists. Gold standard was findings at the original institute by two experts. RESULTS: Mean reading time of small-bowel sections by endoscopists was significantly shorter during process B (expert, 3.1 min; trainee, 5.2 min) compared to process A (expert, 12.2 min; trainee, 20.7 min) (P < 0.001). For 37 mucosal breaks, detection rate by endoscopists did not significantly decrease in process B (expert, 87%; trainee, 55%) compared to process A (expert, 84%; trainee, 47%). Experts detected all eight large lesions (>5 mm), but trainees could not, even when supported by the CNN. CONCLUSIONS: Our CNN-based system for capsule endoscopy videos reduced the reading time of endoscopists without decreasing the detection rate of mucosal breaks. However, the reading level of endoscopists should be considered when using the system.

Changes in components of the neurovascular unit in the retina in a rat model of retinopathy of prematurity.

An impairment of cellular interactions between the elements of the neurovascular unit contributes to the onset and/or progression of retinal diseases. The present study aims to examine how elements of the neurovascular unit are altered in a rat model of retinopathy of prematurity (ROP). Neonatal rats were treated subcutaneously with the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8 to induce ROP. Morphological assessments were performed of blood vessels, astrocytes and neuronal cells in the retina. Aggressive angiogenesis, tortuous arteries and enlarged veins were observed in the retinal vasculature of KRN633-treated (ROP) rats from P14 to P28, compared to age-matched control (vehicle-treated) animals. Morphological abnormalities in the retinal vasculature showed a tendency toward spontaneous recovery from P28 to P35 in ROP rats. Immunofluorescence staining for glial fibrillary acidic protein and Pax2 (astrocyte markers) revealed that morphological changes to and a reduction in the number of astrocytes occurred in ROP rats. The developmental cell death was slightly accelerated in ROP rats; however, no visible changes in the morphology of retinal layers were observed on P35. The abnormalities in astrocytes might contribute, at least in part, to the formation of abnormal retinal blood vessels and the pathogenesis of ROP.

Detection of circulating colorectal cancer cells by a custom microfluid system before and after endoscopic metallic stent placement.

Although the detection of circulating tumor cells (CTCs) should be crucial for future personalized medicine, no efficient and flexible methods have been established. The current study established a polymeric custom-made chip for capturing CTCs with a high efficiency and flexibility. As an example of clinical application, the effects of self-expandable metallic stent (SEMS) placement on the release of cancer cells into the blood of patients with colorectal cancer and bowel obstruction were analyzed. This was assessed as the placement of SEMS may cause mechanical damage and physical force to malignant tissue, increasing the risk of cancer cell release into the bloodstream. The present study examined the number of CTCs using a custom-made chip, before, at 24 h after and at 4 days after SEMS placement in patients with colorectal cancer. The results revealed that, among the 13 patients examined, the number of CTCs was increased in three cases at 24 h after SEMS placement. However, this increase was temporary. The number of CTCs also decreased at 4 days after stent placement in most cases. The CTC chip of the current study detected the number of CD133-positive cancer stem-like cells, which did not change, even in the patient whose total number of CTCs temporarily increased. The results indicated that this custom-made microfluid system can efficiently and flexibly detect CTCs, demonstrating its potential for obtaining information during the management of patients with cancer.

Retinal neuronal cell loss prevents abnormal retinal vascular growth in a rat model of retinopathy of prematurity.

A short-term blockade of the vascular endothelial growth factor (VEGF)-mediated pathway in neonatal rats results in formation of severe retinopathy of prematurity (ROP)-like retinal blood vessels. The present study aimed to examine the role of retinal neurons in the formation of abnormal retinal blood vessels. Newborn rats were treated subcutaneously with the VEGF receptor tyrosine kinase inhibitor, KRN633 (10 mg/kg), or its vehicle (0.5% methylcellulose in water) on postnatal day (P) 7 and P8. To induce excitotoxic loss of retinal neurons, N-methyl-D-aspartic acid (NMDA) was injected into the vitreous chamber of the eye on P9. Changes in retinal morphology, blood vessels, and proliferative status of vascular cells were evaluated on P11 and P14. The number of cells in the ganglion cell layer and the thickness of the inner plexiform layer and inner nuclear layer were significantly decreased 2 days (P11) after NMDA treatment. The pattern and degree of NMDA-induced changes in retinal morphology were similar between vehicle-treated (control) and KRN633-treated (ROP) rats. In ROP rats, increases in the density of capillaries, the tortuosity index of arteries, and the proliferating vascular cells were observed on P14. The expansion of the endothelial cell network was prevented, and the capillary density and the number of proliferating cells were reduced in NMDA-treated retinas of both control and ROP rats. Following NMDA-induced neuronal cell loss, no ROP-like blood vessels were observed in the retinas. These results suggest that retinal neurons play an important role in the formation of normal and ROP-like retinal blood vessels.

Effect of corrective long spinal fusion to the ilium on physical function in patients with adult spinal deformity.

PURPOSE: To identify the effects of corrective long spinal fusion to the ilium on physical function in patients with adult spinal deformity (ASD). METHODS: Thirty patients who underwent corrective long spinal fusion to the ilium were prospectively analysed. Patients were divided into the ++ group [sagittal vertical axis (SVA) ≥ 95 mm and pelvic tilt (PT) ≥ 30°, 14 patients] and 0+ group (SVA <95 mm or PT <30°, 16 patients). Subjects' low back pain [visual analogue scale (VAS) (pain with motion)], muscle strength (knee extensors and hip flexors), balance [timed up and go (TUG)], gait performance [10-metre walking test (10MWT, maximum speed), and 6-minute walk test (6MWT)] were assessed before surgery, at discharge, and 6 and 12 months after the surgery. RESULTS: All study patients had a significant improvement in the VAS score between baseline and at discharge, 6 months postoperatively, and 12 months postoperatively. The values of the TUG and 6MWT significantly improved 12 months postoperatively. The values of the TUG, 10MWT, and 6MWT improved significantly more in the ++ group than in the 0+ group at 12 months. CONCLUSION: Corrective long spinal fusion contributed to improving back pain at discharge and gait ability at 12 months in patients with ASD.