Computer-aided diagnosis of early-stage colorectal cancer using nonmagnified endoscopic white-light images (with videos).

BACKGROUND AND AIMS: Differentiation of colorectal cancers (CRCs) with deep submucosal invasion (T1b) from CRCs with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer-aided diagnosis (CADx) system to establish the diagnosis of early-stage cancers using nonmagnified endoscopic white-light images alone. METHODS: From 5108 images, 1513 lesions (Tis, 1074; T1a, 145; T1b, 294) were collected from 1470 patients at 10 academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Oversampling and focal loss were used to compensate class imbalance of the invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and 2 trainees read the identical testing dataset. RESULTS: At a 90% cutoff for the per-lesion score, CADx showed the highest specificity of 94.4% (95% confidence interval [CI], 91.3-96.6), with 59.8% (95% CI, 48.3-70.4) sensitivity and 87.3% (95% CI, 83.7-90.4) accuracy. The area under the characteristic curve was 85.1% (95% CI, 79.9-90.4) for CADx, 88.2% (95% CI, 83.7-92.8) for expert 1, 85.9% (95% CI, 80.9-90.9) for expert 2, 77.0% (95% CI, 71.5-82.4) for trainee 1 (vs CADx; P = .0076), and 66.2% (95% CI, 60.6-71.9) for trainee 2 (P < .0001). The function was also confirmed on 9 short videos. CONCLUSIONS: A CADx system developed with endoscopic white-light images showed excellent per-lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (Clinical trial registration number: UMIN000037053.).

Regional differences in the prevalence of oral allergy syndrome among Japanese children: A questionnaire-based survey.

BACKGROUND: Oral allergy syndrome (OAS) is characterized by an immediate allergic reaction that mainly or partially affects the oral mucosa, pharynx, or lips, and it is usually caused by ingesting fresh fruits or vegetables. Most patients with OAS also have allergic rhinitis due to pollen. As allergic rhinitis is increasingly prevalent in the Japanese population and the age at disease development is decreasing, morbidity associated with OAS among the younger population is likely to increase. However, there is little information about the prevalence of this disease among Japanese children, specifically the influences of residency in regions with different environments. OBJECTIVE: To investigate the prevalence of OAS and seasonal allergic rhinitis (SAR) among Japanese children and evaluate the relationship between OAS and SAR. METHODS: We administered a questionnaire-based survey among children aged 7-15 years, living in 4 cities in central Japan. RESULTS: The questionnaires were administered to 4103 children and completed by 3365 (82.0%). Overall, 524 children (15.6%) reported OAS-like symptoms after ingesting fruits or vegetables. The prevalence of seasonal SAR and oral symptoms significantly differed among the 4 cities. The total prevalence of oral symptoms co-occurring with SAR was 24.4%, which was significantly higher than the prevalence of symptoms occurring without SAR (10.2%, p < 0.001). CONCLUSIONS: Herein, oral symptoms were more likely to occur in patients with SAR than in those without SAR. The prevalence of SAR and food-induced oral symptoms significantly differed among the regions, suggesting they might be affected by regional differences in lifestyles and flora.

Expression of Leucine-rich Repeat-containing Protein 32 Following Lymphocyte Stimulation in Patients with Non-IgE-mediated Gastrointestinal Food Allergies.

The lymphocyte stimulation test (LST) facilitates the diagnosis of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs). However, LSTs require large volumes of blood and prolonged culture durations. Recently, we found that IL2RA mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with non-IgE-GI-FAs increased after a 24 h stimulation with milk proteins. We designated this gene expression test as the instant peripheral blood allergen stimulation test (iPAST). In this study, we investigated whether other activated T cell-associated genes are superior to IL2RA in the iPAST for the supplementary diagnosis of non-IgE-GI-FAs. After incubating PBMCs with milk proteins for 24 h, the mRNA levels of three genes, LRRC32, TNFRSF4, and CD69, were assessed using quantitative RT-PCR. The diagnostic significance of the mRNA expression was evaluated by analyzing the receiver operating characteristic (ROC) curve. Upon stimulation with α-casein, κ-casein, α-lactalbumin, or a mixture of four milk protein components (Pmix), LRRC32 expression in the PBMCs of 16 patients with non-IgE-GI-FAs was found to be higher than that in their 17 control counterparts, whereas TNFRSF4 and CD69 levels remained unaltered. Except for ß-lactoglobulin and cow's milk (CM), the area under the ROC curve (AUC) for LRRC32 mRNA expression upon stimulation was >0.7, which validated the diagnostic ability of this test. Notably, α-casein and Pmix had higher AUC scores of 0.820 and 0.842, respectively, than other antigens. iPAST assessed by LRRC32 as well as IL2RA may be useful for the supplementary diagnosis of non-IgE-GI-FAs as an alternative to LSTs and provide insight into the pathogenesis of non-IgE-GI-FAs.

Severity scales of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) are one type of food allergy found in neonates and infants. Few reports have defined the severity of non-IgE-GI-FAs in these populations. METHODS: Grading scales of the severity of non-IgE-GI-FAs according to extra-GI symptoms, such as poor weight gain, as well as systemic symptoms, including fever and shock, were developed and retrospectively applied to patients with non-IgE-GI-FAs. The relationship between the severity of non-IgE-GI-FAs and both clinical and laboratory findings were examined. RESULTS: Elevation of C-reactive protein levels and a decrease in total protein and albumin were observed in accordance with allergy severity. In an endoscopic examination, inflammatory findings were confirmed in large areas of the colonic mucosa in case of higher severity levels, and infiltration of inflammatory cells other than eosinophils was found in the severest grade. Extensively hydrolyzed milk or amino acid-based milk was required for all patients with the severest grade. In addition, the timing of acquiring tolerance tended to be late for this grade. CONCLUSIONS: Classification and determination of the severity of non-IgE-GI-FAs in neonates and infants may not only contribute to elucidation of the pathogenesis but may also be useful in the clinical setting.

[SWITCHING BIOLOGICS LED TO GOOD CONTROL IN SEVERE CHILDHOOD ASTHMA: A CASE REPORT].

The two biologic therapies, anti-IgE (omalizumab) and anti-IL-5 antibodies (mepolizumab), are used in the treatment of severe pediatric asthma. We present here a case study of a 13-year-old girl with severe asthma who switched from omalizumab to mepolizumab therapy and achieved good control over her asthma. The patient was diagnosed with asthma at one year of age and presented with poor disease control, even while taking high doses of inhaled corticosteroids (ICS). As such, she was considered to have severe persistent asthma. At 10 years old, she began omalizumab therapy which improved asthma control. However, after two years of this therapy, she manifested frequent acute exacerbations. At 12 years old, she switched to mepolizumab and has since maintained good control of asthma. Additionally, total serum IgE levels and peripheral eosinophil counts decreased. As the underlying mechanisms of omalizumab and mepolizumab therapy are distinct, it is recommended to use either one if the other proves ineffective.

A prospective randomized study of the use of an ultrathin colonoscope versus a pediatric colonoscope in sedation-optional colonoscopy.

BACKGROUND: Ultrathin colonoscopes (UTC) reportedly produce less pain during colonoscopy than standard colonoscopes. The aim of this study was to assess the tolerability of an UTC compared with that of a pediatric colonoscope. METHODS: A total of 270 adult patients scheduled to undergo colonoscopy were randomized, with 134 allocated to the UTC group and 136 to the pediatric colonoscope group. Pain was assessed using a visual analog scale. For all procedures, sedation was administered only if requested. Overall pain, rate and time of cecal and terminal ileum intubation, number of patients requesting sedation, adenoma detection rates (ADR), and rate of complications were measured and analyzed. RESULTS: Among all patients, the medians of maximum pain and overall pain were significantly lower in the UTC group than in the pediatric colonoscope group (23 vs. 38, P < 0.001; 12 vs. 22, P = 0.0003, respectively). Significantly fewer patients requested sedation in the UTC group than in the pediatric colonoscope group (1.4 vs. 6.6%; P = 0.0269). No significant differences were seen in either the rate and time of successful cecal and terminal ileum intubation, or in other procedure-related outcomes, including ADR. CONCLUSIONS: Compared with a pediatric colonoscope, the UTC was associated with reduced overall and maximum pain during colonoscopy, with no difference in ADR.

Intrahepatic cholangiocarcinoma producing granulocyte colony-stimulating factor and parathyroid hormone-related protein.

A 78-year-old man was referred to our hospital with suspected liver abscess. Fever and inflammatory reaction resolved after percutaneous drainage and administration of antibiotics. However, leukocyte count was remarkably increased, and hypercalcemia was noted. The liver mass was also enlarged, as observed in the follow-up abdominal CT scans. Therefore, a percutaneous needle biopsy was performed, and the histopathological findings indicated the presence of adenocarcinoma. Additional blood examination revealed high serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). Lastly, the patient was diagnosed with cholangiocarcinoma producing G-CSF and PTHrP. Chemoradiotherapy with S-1 was initiated, which was partially effective. However, the patient died 134 days after initiating the therapy. Only two cases of cholangiocarcinoma producing G-CSF and PTHrP have been reported to date. Here we reported an additional case of cholangiocarcinoma producing G-CSF and PTHrP.

A Strategy against the Osteonecrosis of the Jaw Associated with Nitrogen-Containing Bisphosphonates (N-BPs): Attempts to Replace N-BPs with the Non-N-BP Etidronate.

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) can occur when enhanced bone-resorptive diseases are treated with nitrogen-containing BPs (N-BPs). Having previously found, in mice, that the non-N-BP etidronate can (i) reduce the inflammatory/necrotic effects of N-BPs by inhibiting their intracellular entry and (ii) antagonize the binding of N-BPs to bone hydroxyapatite, we hypothesized that etidronate-replacement therapy (Eti-RT) might be useful for patients with, or at risk of, BRONJ. In the present study we examined this hypothesis. In each of 25 patients receiving N-BP treatment, the N-BP was discontinued when BRONJ was suspected and/or diagnosed. After consultation with the physician-in-charge and with the patient's informed consent, Eti-RT was instituted in one group according to its standard oral prescription. We retrospectively compared this Eti-RT group (11 patients) with a non-Eti-RT group (14 patients). The Eti-RT group (6 oral N-BP patients and 5 intravenous N-BP patients) and the non-Eti-RT group (5 oral N-BP patients and 9 intravenous N-BP patients) were all stage 2-3 BRONJ. Both in oral and intravenous N-BP patients (particularly in the former patients), Eti-RT promoted or tended to promote the separation and removal of sequestra and thereby promoted the recovery of soft-tissues, allowing them to cover the exposed jawbone. These results suggest that Eti-RT may be an effective choice for BRONJ caused by either oral or intravenous N-BPs and for BRONJ prevention, while retaining a level of anti-bone-resorption. Eti-RT may also be effective at preventing BRONJ in N-BP-treated patients at risk of BRONJ. However, prospective trials are still required.

Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis.

Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion-induced allergic contact dermatitis.

A case of a child with an APC pathogenic mutation, aberrant expression of splice variants and positive family history of FAP.

Familial adenomatous polyposis is an autosomal dominant hereditary disease characterized by the appearance of hundreds to thousands of colorectal adenomatous polyps; if left untreated, there is nearly a 100% lifetime risk of colorectal cancer. In the present case, adenomatous polyps were observed at 6 years of age. Unlike our previous assumption, adenomatous polyps were detected by colonoscopy at <10 years of age. Considering the clinical importance of early diagnosis, we report this case involving germline adenomatous polyposis coli mutation (c.1958G > C, GenBank: M74088.1) that caused an increase in the isoform without exon 15. Although this isoform has been reported previously, it remains controversial whether the variant is pathogenic or not because it was observed both in patients with familial adenomatous polyposis and in normal controls. Nonetheless, due to quantitative distortion of splice variants in adenomatous polyposis coli transcripts and the early development of adenomatous polyps, we believe that this variant may be pathogenic.

Factors affecting the technical difficulty and clinical outcome of endoscopic submucosal dissection for colorectal tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) for colorectal tumors is technically difficult due to the anatomy of the large intestine, with its narrow lumen, thin walls, and redundancy. Here, we assessed factors associated with incomplete resection and difficult colorectal ESD. METHODS: Between November 2009 and April 2013, we performed ESD on 151 consecutive colorectal tumors in 147 patients. We evaluated the clinical outcomes of all cases and conducted multiple logistic regression analysis of the following factors related to incomplete resection and difficult procedure: age, gender, location (right colon, left colon or rectum), tumor size (diameter ≥40 or <40 mm), operation time, morphology [granular-type laterally spreading tumor (LST-G), non-granular-type laterally spreading tumor (LST-NG), or protruded type], fibrosis, and paradoxical movement during the procedure. A procedure that required more than 120 min was defined as a difficult colorectal ESD. RESULTS: Average tumor size was 32.1 ± 10.7 mm, and the average procedure length was 71.8 ± 49.5 min. The rate of en bloc resection was 94.7%, while that of en bloc curative resection was 86.8%. Perforation occurred in 1.3% of the ESD procedures. Multivariate logistic regression analysis revealed that only severe fibrosis [odds ratio (OR) 4.51; 95% confidence interval (CI) 1.36-14.91, p = 0.014] contributed to incomplete resection and that a tumor size exceeding 40 mm (OR 5.73 [95% CI 1.66-19.74], p = 0.006), severe fibrosis (OR 23.31 [95% CI 6.59-82.54], p < 0.001), and paradoxical movement (OR 4.26 [95% CI 1.11-16.44], p = 0.035) were independent factors exacerbating the difficulty of colorectal ESD. CONCLUSIONS: Severe fibrosis contributed to both incomplete resection and difficult colorectal ESD. Larger tumor size and paradoxical movement during the procedure were independent factors contributing to the difficulty of colorectal ESD. These factors might enable endoscopists to develop strategies for treating colorectal ESD.

Evidence of brain atrophy detected on magnetic resonance imaging is associated with failure of acquisition of the ability for insulin self-injection.

Type 2 diabetes is known to be associated with cognitive dysfunction and an increased risk of dementia in the elderly. Although it is one of the most efficacious therapies in diabetic patients, insulin therapy requires that patients learn to inject themselves with insulin. We studied the association between brain atrophy detected on magnetic resonance imaging (MRI) of the head and the ability of type 2 diabetic patients to learn self-injection. MRI of the head was performed in 41 type 2 diabetic patients aged 60-80 years old. The area of the cerebrum relative to the intracranial area (the brain parenchymal fraction: BPF) was calculated with the WinROOF software program. Learning ability was assessed by counting the number of training sessions needed to acquire the ability to self-inject. Patients were divided into a failure group and success group. The average age was significantly higher (P < 0.001) and the BPF was significantly lower (P < 0.001) in the failure group (patients requiring 14 or more training sessions) than the success group (the remaining patients). A binary logistic regression analysis revealed that both age and BPF were independent predictors of success/failure in acquiring self-injection ability (P = 0.005 and P = 0.031, respectively). We conclude that brain atrophy on MRI is an important determinant of the ability of patients to learn insulin self-injection.

Evidence of brain atrophy detected on magnetic resonance imaging is associated with failure of acquisition of the ability for insulin self-injection.

Type 2 diabetes is known to be associated with cognitive dysfunction and an increased risk of dementia in the elderly. Although it is one of the most efficacious therapies in diabetic patients, insulin therapy requires that patients learn to inject themselves with insulin. We studied the association between brain atrophy detected on magnetic resonance imaging (MRI) of the head and the ability of type 2 diabetic patients to learn self-injection. MRI of the head was performed in 41 type 2 diabetic patients aged 60-80 years old. The area of the cerebrum relative to the intracranial area (the brain parenchymal fraction: BPF) was calculated with the WinROOF software program. Learning ability was assessed by counting the number of training sessions needed to acquire the ability to self-inject. Patients were divided into a failure group and success group. The average age was significantly higher (P < 0.001) and the BPF was significantly lower (P < 0.001) in the failure group (patients requiring 14 or more training sessions) than the success group (the remaining patients). A binary logistic regression analysis revealed that both age and BPF were independent predictors of success/failure in acquiring self-injection ability (P = 0.005 and P = 0.031, respectively). We conclude that brain atrophy on MRI is an important determinant of the ability of patients to learn insulin self-injection.

Outcomes and Recurrence Rate of Esophageal Varices after Endoscopic Treatment in Patients with Alcoholic Cirrhosis and Viral Cirrhosis.

BACKGROUND: The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC). METHODS: We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis. RESULTS: The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively). CONCLUSION: When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.

Neuroendoscopic cyst fenestration for delayed enlargement of perianeurysmal cyst formation through long-term follow-up after endovascular treatment: A case report and review of literature.

Background: Perianeurysmal cyst formation after endovascular treatment of cerebral aneurysms is a rare complication; however, the number of reports has gradually increased in recent years due to the development of several endovascular treatments. Case Description: We present a case of delayed perianeurysmal cyst enlargement 8 years after endovascular treatment for multiple recurrences of a large cerebral aneurysm in the anterior communicating artery. The patient presented with obstructive hydrocephalus caused by an enlarged perianeurysmal cyst. The patient underwent cyst fenestration using neuroendoscopy and ventriculoperitoneal shunting, recovered from the clinical symptoms, and had a good prognosis. Histopathological findings showed that the cyst wall contained a fibrotic layer under the monoependymal layer with hemosiderosis without evidence of neovascularization or inflammatory cell infiltration. These findings suggest that the origin of the perianeurysmal cyst wall is not the aneurysm itself but the adjacent brain tissue. Conclusion: Perianeurysmal cysts can develop during long-term follow-up, and clinicians should consider surgical treatment, including cyst fenestration, using neuro-endoscopy if the cyst presents with clinical symptoms.

Time to symptom onset and manual reduction outcomes as predictors of bowel viability in incarcerated obturator hernias.

The current study aimed to identify the indications for manual reduction in incarcerated obturator hernias (OH). Further, whether time to symptom onset and manual reduction outcomes can be predictors of bowel viability and the need for bowel resection in incarcerated OH were examined. This retrospective study included 26 patients with incarcerated OH who underwent surgery. All patients underwent manual reduction, and computed tomography scan after manual reduction confirmed hernia release. Multivariate analyses were performed to determine the predictors of bowel resection. The bowel resection group had a significantly longer average time to symptom onset than the nonbowel resection group (88 vs 36 h). Further, the bowel resection group was more likely to have failed manual reduction than the nonbowel resection group. A time to symptom onset of ≥ 72 h and failed manual reduction were significant predictors of bowel viability. Age, sex, hernia localization, American Society of Anesthesiologists physical status score, and laboratory findings did not differ significantly between the bowel resection and nonbowel resection groups. Time to symptom onset and manual reduction outcomes are significant predictors of bowel viability in incarcerated OH. Patients with a time to symptom onset of ≥ 72 h and failed manual reduction require surgical evaluation due to a high risk of bowel nonviability. Therefore, a cautious approach is required in the management of OH, and further research on optimized treatment protocols should be conducted.