Impact of an artificial intelligence-aided endoscopic diagnosis system on improving endoscopy quality for trainees in colonoscopy: Prospective, randomized, multicenter study.

OBJECTIVE: This study was performed to evaluate whether the use of CAD EYE (Fujifilm, Tokyo, Japan) for colonoscopy improves colonoscopy quality in gastroenterology trainees. METHODS: The patients in this multicenter randomized controlled trial were divided into Group A (observation using CAD EYE) and Group B (standard observation). Six trainees performed colonoscopies using a back-to-back method in pairs with gastroenterology experts. The primary end-point was the trainees' adenoma detection rate (ADR), and the secondary end-points were the trainees' adenoma miss rate (AMR) and Assessment of Competency in Endoscopy (ACE) tool scores. Each trainee's learning curve was evaluated using a cumulative sum (CUSUM) control chart. RESULTS: We analyzed data for 231 patients (Group A, n = 113; Group B, n = 118). The ADR was not significantly different between the two groups. Group A had a significantly lower AMR (25.6% vs. 38.6%, P = 0.033) and number of missed adenomas per patient (0.5 vs. 0.9, P = 0.004) than Group B. Group A also had significantly higher ACE tool scores for pathology identification (2.26 vs. 2.07, P = 0.030) and interpretation and identification of pathology location (2.18 vs. 2.00, P = 0.038). For the CUSUM learning curve, Group A showed a trend toward a lower number of cases of missed multiple adenomas by the six trainees. CONCLUSION: CAD EYE did not improve ADR but decreased the AMR and improved the ability to accurately locate and identify colorectal adenomas. CAD EYE can be assumed to be beneficial for improving colonoscopy quality in gastroenterology trainees. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000044031).

Polybacterial Iliopsoas Muscle Abscess as an Indication for Early Diagnosis of Crohn's Disease.

BACKGROUND Crohn disease (CD) is a chronic, relapsing inflammatory bowel disease characterized by penetrations or fistulae in the gastrointestinal tract and abscesses in the surrounding tissues. Diagnosis of CD is difficult with an iliopsoas muscle abscess (IMA) as an initial presentation. CASE REPORT A 22-year-old Japanese man had right hip pain 17 days prior to admission. Because of worsening pain, he was admitted to our hospital. Physical examination revealed limitation of his right hip motion and a positive right psoas sign. Abdominal contrast-enhanced computed tomography (CT) revealed a large right IMA. Continuous drainage, which revealed polymicrobial pus, with intravenous administration of antibiotics dramatically decreased the size of the IMA. The drainage tube was removed on hospitalization day 9 because barium enema and contrast radiography of the abscess through the drainage tube showed no fistula. However, on day 19 of hospitalization, the IMA was redetected by abdominal CT. Continuous abscess drainage was resumed, and the third contrast radiograph of the abscess revealed contrast medium flow into the small intestine. Colonoscopy detected stenoses and circumferential ulceration of the terminal ileum. Histopathological examination of the ileum biopsy showed histocyte aggregation with lymphocyte or plasmacyte infiltration of the lamina propria, compatible with a CD diagnosis. Laparoscopic ileocecal resection was performed on day 64 of hospitalization. CONCLUSIONS Penetration of the intestinal tract caused by CD should be suspected in a patient with a polymicrobial IMA. It is essential to identify the fistula and subsequently perform surgical resection of the affected intestinal area.

Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn's disease: tertiary centers experience in Japan.

PURPOSE: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab. METHODS: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3 mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed. RESULTS: The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2 years) and higher baseline serum albumin levels (≥ 3.1 g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19 mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found. CONCLUSION: A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels.

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.).

Gastrointestinal bleeding after endoscopic mucosal resection in a case of Peutz-Jeghers syndrome with hypofibrinogenemia: A case report.

Backgroud: Peutz-Jegers syndrome (PJS) is an autosomal dominant hereditary disorder characterized by hamartomatous polyposis of the entire gastrointestinal tract. Fibrinogen (Fbg) is synthesized by the liver, and hypofibrinogenemia is often asymptomatic and manifests with bleeding after trauma or invasive surgical procedures. Here, we present a case of a pediatric patient with PJS and hypofibrinogenemia who manifested with gastrointestinal bleeding after endoscopic mucosal resection (EMR) of small intestinal polyps. Case Presentation: An 11-year-old boy with PJS was referred to our hospital. Since his mother was diagnosed with PJS, with black pigments being observed on his lips, mouth, and limbs, he underwent upper and lower gastrointestinal endoscopy at the age of 8 years at a previous hospital. EMR for duodenal polyp was performed, and the pathological findings were consistent with hamartoma. His Fbg level was 117 mg/dl at the time, with no post-bleeding being detected after EMR. The small intestine was not assessed at the prior facility and was left neglected for three years. At our hospital, small intestine fluoroscopy was performed and revealed a polyp in the jejunum, and abdominal computed tomography showed two polyps and intussusception. On double-balloon enteroscopy, the resected polyps were hamartoma with diameters of 20 and 30 mm. The patient's Fbg level was 107 mg/dl. The day after EMR, he had melena and black stools. He was diagnosed with post-EMR bleeding and started to stop eating, and hemostatic agents were given. His hemoglobin level dropped to 9.2 g/dl the next day. Genetic testing for congenital Fbg deficiency revealed a heterozygous pathogenic variant in fibrinogen gamma chain Exon 10. Therefore, he was diagnosed with concurrent hypofibrinogenemia and PJS. Conclusion: To the best of our knowledge, this is the first reported case with concurrent PJS and hypofibrinogenemia. In patients with PJS, hypofibrinogenemia should be considered as one of the risk factors of postoperative bleeding during polypectomy, and appropriate prophylactic measures should be taken.

Small intestinal hamartomatous polyp due to Peutz-Jeghers syndrome in middle childhood.

Small-bowel surveillance is recommended from the age of 8 years in asymptomatic individuals with Peutz-Jeghers syndrome. Because intussusception and risk of strangulated ileus were noted in an 11-year-old patient, small-bowel surveillance should be reliably performed from the age of 8 years to avoid urgent surgery.

Estimating colorectal polyp size with a virtual scale endoscope and visual estimation during colonoscopy: Prospective, preliminary comparison of accuracy.

The virtual scale endoscope (VSE) is a new endoscope that helps estimate the size of neoplasms in the gastrointestinal tract. We compared the accuracy of polyp size estimation by VSE with that of visual estimation. A dual center prospective study was conducted in two Japanese academic endoscopy units. Ten endoscopists (five trainees and five experts) estimated the size of 20 simulated polyps in four colon phantoms during colonoscopy by two methods: conventional visual estimation and estimation by VSE. The primary endpoint was the relative accuracy in relation to true polyp size according to visual estimation and VSE estimation during colonoscopy. The secondary endpoint was the required time (the time needed to measure in each procedure). The mean values of the primary end-point were 62.5% for visual estimation and 84.0% for VSE estimation; hence the result differed significantly (95% confidence interval 18.3-24.7; P < 0.001). The mean of required times was significantly longer for estimation by VSE (6.4 min) than that by visual estimation (2.9 min; P < 0.001). The accuracy of colorectal polyp size estimation was superior with VSE than with visual estimation during colonoscopy. In the future, VSE should be evaluated in actual clinical settings, including the time required for size estimation.

Collagenous Colitis Possibly Associated with Dipeptidyl Peptidase-4 Inhibitor.

A 60-year-old man with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor was referred to our hospital because of his refractory watery diarrhea. Ileocolonoscopy revealed increased capillary growth, fine granular mucosa, and longitudinal mucosal tears mainly in the left side of the colon. A bioptic examination revealed thickened subepithelial collagen bands, thus confirming the diagnosis of collagenous colitis. Systemic steroid therapy was initiated, but his symptoms recurred when tapering the steroid. However, withdrawal of the DPP-4 inhibitor was successful even after the cessation of steroid therapy. We therefore considered his collagenous colitis to have been caused by the DPP-4 inhibitor.

Efficacy of elobixibat as bowel preparation agent for colonoscopy: Prospective, randomized, multi-center study.

BACKGROUND AND AIM: Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG-Asc) solution versus the combination of sodium picosulfate and 1-L PEG-Asc solution as bowel preparation for colonoscopy. METHODS: This multi-center, randomized, observer-blinded, non-inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1-L PEG-Asc group (group A) or the sodium picosulfate plus 1-L PEG-Asc group (group B). The quality of the bowel cleansing level was assessed by the Boston Bowel Preparation Scale (BBPS) and compared the bowel cleansing level between the groups. Data regarding bowel preparation time, patients' tolerability, and adverse events were also analyzed. RESULTS: Data for 196 patients (99 in group A and 97 in group B) were analyzed finally. BBPS was comparable between group A and B (8.3 ± 0.9 vs. 8.3 ± 0.7; P = 0.88). Consequently, the adequate bowel preparation rate in groups A and B was 95.0% and 99.0%, respectively (-4.0%, 95% CI -9.3 to 1.5). Bowel preparation time in group A was similar to that in group B (348.2 ± 79.8 min vs. 330.8 ± 82.5 min; P = 0.13), whereas, sleep disturbance was significantly less frequent in group A than in group B (10.2% vs. 22.7%; P = 0.02). CONCLUSIONS: The combination of elobixibat and 1-L PEG-Asc can be considered an alternative bowel preparation for colonoscopy considering the equivalent bowel cleansing effect and less frequent sleep disturbance. The Japan Registry of Clinical Trials (jRCTs41180026).

Lifestyle- and comorbidity-related factors for the prescription of proton pump inhibitors after Helicobacter pylori eradication in Japan.

BACKGROUND AND AIM: The aim of the present study was to examine the lifestyle- and comorbidity-related determinant factors of the prescription of proton pump inhibitors (PPIs) for patients in whom Helicobacter pylori has been eradicated, and to evaluate the relationship between PPI prescription and the severity of endoscopic esophagitis. METHODS: This retrospective study included patients who underwent H. pylori eradication from May 2012 to September 2016 at Saiseikai Karatsu Hospital. All patients received upper gastrointestinal endoscopy before H. pylori eradication. Patients with open peptic ulcers and/or malignant diseases were excluded, and a final total of 389 patients were evaluated. Medical records were reviewed to determine the prescription of PPIs after H. pylori eradication, lifestyle-related factors, and comorbidities. Lifestyle-related factors were confirmed by a questionnaire. RESULTS: PPIs were administered to 124 of 389 patients (31.9%). The only lifestyle-related risk factor for the prescription of PPIs after H. pylori eradication was older age (P < 0.01). Hypertension increased the prescription of PPIs (P = 0.034). The prescription of PPIs was not influenced by the presence of grade A esophagitis, whereas the PPI prescription rate was significantly increased in patients with grades B/C/D endoscopic esophagitis (P < 0.01). The grade of chronic gastritis before H. pylori eradication had no effect on the prescription of PPIs. CONCLUSION: The lifestyle- and comorbidity-related risk factors for the prescription of PPIs after H. pylori eradication were older age and hypertension, while mild endoscopic esophagitis had no influence on PPI prescription.

Tissue-specific Physical and Biological Microenvironments Modulate the Behavior of Cervical Squamous Cell Carcinoma.

The mechanisms controlling the aggressiveness and survival of cervical SCC cells remain unclear. We investigated how the physical and biological microenvironments regulate the growth, apoptosis and invasiveness of cervical cancer cells. Dynamic flow and air exposure were evaluated as physical microenvironmental factors, and stromal fibroblasts were evaluated as a biological microenvironmental factor. To investigate any regulatory effects of these microenvironmental factors, we established a new culture model which concurrently replicates fluid streaming, air exposure and cancer-stromal interactions. Three cervical cancer cell lines were cultured with or without NIH 3T3 fibroblasts. Air exposure was realized using a double-dish culture system. Dynamic flow was created using a rotary shaker. Dynamic flow and air exposure promoted the proliferative activity and decreased the apoptosis of cervical cancer cells. Fibroblasts regulated the invasive ability, growth and apoptosis of cervical cancer cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by dynamic flow, air exposure and cellular interactions, depending on the cervical cancer cell type. This study demonstrates that the physical and biological microenvironments interact to regulate the aggressiveness and survival of cervical cancer cells. Our simple culture system is a promising model for developing further treatment strategies for various types of cancer.

Safety and Efficacy of the Noncessation Method of Antithrombotic Agents after Emergency Endoscopic Hemostasis in Patients with Nonvariceal Upper Gastrointestinal Bleeding: A Multicenter Pilot Study.

Background and Aims: The present study aimed to clarify the safety and efficacy of the noncessation method of antithrombotic agents after emergency endoscopic hemostasis in patients with nonvariceal upper gastrointestinal bleeding (UGIB). Methods: In this multicenter, prospective, pilot study, we performed emergency endoscopic hemostasis for nonvariceal UGIB in patients taking antithrombotic agents and resumed the medications without a cessation period (group A). The clinical characteristics, types of antithrombotic agents, UGIB etiology, treatment outcome, and adverse events were evaluated. We used propensity score matching to compare treatment outcomes and adverse events with our previous cohort (group B) in whom antithrombotic agents were transiently discontinued after emergency endoscopic hemostasis. Results: Forty-three consecutive patients were prospectively enrolled. The main antithrombotic agents were low-dose aspirin and direct oral anticoagulants; 11 patients (25.6%) were taking multiple antithrombotics. Peptic ulcers were the main cause of bleeding (95.4%). Endoscopic hemostasis was successful in all patients and the incidence of rebleeding within a month was 7.0%. Propensity score matching created 40 matched pairs. Endoscopic hemostasis was performed by soft coagulation significantly more frequently in group A than in group B (97.5% versus 60.0%, P < 0.001). Neither the rebleeding rate within a month nor thromboembolic event rate was different between the two groups. However, the mean duration of hospitalization was significantly shorter in group A than in group B (8.6 ± 5.2 d versus 14.4 ± 7.1 d, P < 0.001). Conclusions: Antithrombotic agents possibly can be continued after successful emergency endoscopic hemostasis for nonvariceal UGIB.

Collagen Vitrigel Membrane-Coated Nylon Line Prevents Stenosis After Conization of the Cervix Uteri.

Cervical stenosis is a postoperative complication of conization for uterine cervical malignancy, but a standard method of preventing this complication has yet to be established. Collagen vitrigel is a collagen-based biomaterial that has antifibrotic and epithelization promoting actions. We evaluated the antistenotic effect of an indwelling collagen vitrigel membrane-coated nylon line (CVNL) after cervical conization in rabbits. In one group of rabbits, a CVNL was placed in the cervical canal after conization. In another group, a nylon line without a collagen coating was placed in the cervical canal after conization. The control group underwent cervical conization without placement of a device. The control (conization alone) and nylon (conization plus indwelling nylon line) groups exhibited cervical swelling. Rabbits in the CVNL group (cervical conization plus indwelling CVNL in the xerogel state) had a normal cervical surface. The cervical canal in the control group was enlarged and showed cystic changes attributed to cervical stenosis. The nylon group exhibited a trend toward cervical canal dilatation. In the CVNL group, the cervical canal was normal and did not show cystic dilatation. Fibrosis occurred to a lesser degree in the nylon group than in the control group, and the CVNL group exhibited minimal interstitial fibrosis. The control and nylon groups showed increased numbers of myofibroblasts in the regenerated cervix, but few myofibroblasts were observed in the CVNL group. Abundant collagen type III was observed in regenerated cervical tissue in the control and nylon groups but not in the CVNL group. The number of proliferative mesenchymal cells in the regenerated cervix was lowest in the CVNL group. The expressions of connective tissue growth factor (CTGF, a regulator of fibroblast growth and extracellular matrix secretion), extracellular signal-regulated protein kinases 1 and 2, and c-Jun N-terminal kinase (which are involved in the induction of CTGF by transforming growth factor-ß) were lower in the CVNL group than in the control or nylon groups. This study describes an indwelling CVNL that prevents cervical stenosis and cystic changes after conization. These effects were likely mediated by inhibition of fibrosis, myofibroblast emergence, CTGF expression, and collagen type III deposition in regenerating cervix. Impact statement Collagen vitrigel is a high-density collagen material that promotes epithelization, inhibits fibrosis, and suppresses inflammation in regenerating tissue. We evaluated whether a collagen vitrigel membrane-coated nylon line would prevent cervical stenosis after conization in the rabbit. We found that an indwelling collagen vitrigel membrane-coated nylon line prevented cervical canal stenosis and cystic changes after cervical conization by inhibiting fibrosis, myofibroblast emergence, connective tissue growth factor expression, and collagen type III deposition in the regenerating cervix. Our device has potential as a new method of preventing cervical canal fibrosis and stenosis after conization for cervical cancer.

Decline incidence in upper gastrointestinal bleeding in several recent years: data of the Japan claims database of 13 million accumulated patients.

This study was to examine the recent trends in upper gastrointestinal bleeding in Japan using a large-scale real-world database. The incidence of upper gastrointestinal bleeding was evaluated in the Japan Medical Data Center claims database of 13,019,713 patients aged 20 to 74 years with traceability for 3 months from 2009 to 2014. The incidence was compared with peptic ulcers and gastroesophageal reflux disease. The prescription of medications was also evaluated. The incidence of bleeding was 0.137%, 0.121%, 0.113%, 0.106%, 0.099%, and 0.105% during 2009 to 2014 with a time-dependent decline (p<0.001). Peptic ulcers (>10 times higher than the incidence of bleeding) decreased with time (p<0.001), whereas gastroesophageal reflux disease increased (p = 0.006). Upper gastrointestinal bleeding was higher in male patients and older patients (60-74 years old) (p<0.001 respectively). The prescription rate of antithrombotic medications and proton pump inhibitors increased from 2009 to 2014 (p<0.001 respectively). The incidence of upper gastrointestinal bleeding decreased from 2009 to 2014 in this relatively large-scale real-world database in Japan, concomitant with the decrease in peptic ulcers. The decreased incidence might have been due to changes in the disease structure and therapeutic strategies over time.

Cellular and physical microenvironments regulate the aggressiveness and sunitinib chemosensitivity of clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most predominant type of kidney cancer in adults and is responsible for approximately 85% of clinical cases. The tumor-specific microenvironment includes both cellular and physical factors, and it regulates the homeostasis and function of cancer cells. Perirenal adipose tissue and tumor-associated macrophages are the major cellular components of the RCC microenvironment. The RCC microvasculature network generates interstitial fluid flow, which is the movement of fluid through the extracellular compartments of tissues. This fluid flow is a specific physical characteristic of the microenvironment of RCC. We hypothesized that there may be an interaction between the cellular and physical microenvironments and that these two factors may play an important role in regulating the behavior of RCC. To elucidate the effects of adipose tissue, macrophages, and fluid flow stimulation on RCC and to investigate the relationships between these factors, we used a collagen gel culture method to generate cancer-stroma interactions and a gyratory shaker to create fluid flow stimulation. Adipose-related cells, monocytes, and fluid flow influenced the proliferative potential and invasive capacity of RCC cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by both fluid flow and cellular interactions between RCC and adipose tissue fragments or macrophages. Fluid flow stimulation synergistically enhanced the anti-proliferative effect of sunitinib on RCC cells, but macrophages abolished the synergistic anti-proliferative effect related to fluid flow stimulation. In conclusion, we established a reconstructed model to investigate the cellular and physical microenvironments of RCC in vitro. Our alternative culture model may provide a promising tool for further therapeutic investigations into many types of cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

A Study on the Status of Proton Pump Inhibitor Prescriptions Using Diagnosis Procedure Combination Data in Japan.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are widely used for the management of acid-related diseases. This study aimed to clarify the status of PPI use in hospitalized patients. METHOD: A retrospective observational study was performed. We analyzed PPI prescription data for the past 8 years (2009-2016) using Diagnosis Procedure Combination survey data from approximately 10,000 patients per year at Saga University Hospital. We investigated the trend in the number of hospitalized patients who were prescribed PPI for the past 8 years and the changes in patient characteristics. RESULTS: We identified 11,009 patients using PPIs throughout the study period. PPI prescription proportions significantly increased over the study period. The use of PPIs increased steadily with increasing age. The proportion of PPIs prescribed was 1.3-times higher among men than compared with women. In most clinical departments, the number of patients prescribed PPIs was up to 3 times higher in the second half of the period (2013-2016) compared with the first half of the period (2009-2012). The number of patients taking concomitant PPIs and anticoagulants or dual antithrombotic combination therapy increased. CONCLUSION: PPI use has increased substantially in hospitalized patients. The prevalence of PPI prescription by doctors other than gastroenterologists also increased.