Improving bowel preparation for colonoscopy with a smartphone application driven by artificial intelligence.

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.

A long noncoding RNA-microRNA expression signature predicts metastatic signature in pheochromocytomas and paragangliomas.

PURPOSE: In hopes of discovering new markers for metastatic or aggressive phenotypes of pheochromocytomas and paragangliomas (PCPG), we analyzed the noncoding transcriptome from patient gene expression data in The Cancer Genome Atlas. METHODS: Differential expression of miRNAs was observed between PCPG molecular subtypes. We specifically characterized candidate miRNAs that are upregulated in pseudohypoxic PCPGs with mutations in succinate dehydrogenase complex subunits, B and/or D (SDHB and/or SDHD, respectively), which are mutations associated with unfavorable clinical outcomes. RESULTS: Our computational analysis identified four candidate miRNAs that showed elevated expression in metastatic compared to non-metastatic PCPGs: miR-182, miR-183, miR-96, and miR-383. We also found six candidate lncRNAs harboring opposite expression patterns from the miRNAs when we analyzed the expression profiles of their predicted target lncRNAs. Three of these lncRNA candidates, USP3-AS1, LINC00877, and AC009312.1, were validated to have reduced expression in metastatic compared to non-metastatic PCPGs. Finally, using univariate and multivariate analysis, we found miRNA miR-182 to be an independent predictor of metastasis-free survival in PCPGs. CONCLUSIONS: We identified candidate miRNA and lncRNAs associated with metastasis-free survival in PCPGs.

Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy.

Immunotherapy has become an essential component in cancer treatment. However, the majority of solid metastatic cancers, such as pheochromocytoma, are resistant to this approach. Therefore, understanding immune cell composition in primary and distant metastatic tumors is important for therapeutic intervention and diagnostics. Combined mannan-BAM, TLR ligand, and anti-CD40 antibody-based intratumoral immunotherapy (MBTA therapy) previously resulted in the complete eradication of murine subcutaneous pheochromocytoma and demonstrated a systemic antitumor immune response in a metastatic model. Here, we further evaluated this systemic effect using a bilateral pheochromocytoma model, performing MBTA therapy through injection into the primary tumor and using distant (non-injected) tumors to monitor size changes and detailed immune cell infiltration. MBTA therapy suppressed the growth of not only injected but also distal tumors and prolonged MBTA-treated mice survival. Our flow cytometry analysis showed that MBTA therapy led to increased recruitment of innate and adaptive immune cells in both tumors and the spleen. Moreover, adoptive CD4+ T cell transfer from successfully MBTA-treated mice (i.e., subcutaneous pheochromocytoma) demonstrates the importance of these cells in long-term immunological memory. In summary, this study unravels further details on the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination.

Therapeutic Targeting of SDHB-Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid.

PURPOSE: Pheochromocytomas and paragangliomas (PCPG) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit (SDHB) have a poor prognosis and frequently develop metastatic lesions. SDHB-mutated PCPGs exhibit dysregulation in oxygen metabolic pathways, including pseudohypoxia and formation of reactive oxygen species, suggesting that targeting the redox balance pathway could be a potential therapeutic approach. EXPERIMENTAL DESIGN: We studied the genetic alterations of cluster I PCPGs compared with cluster II PCPGs, which usually present as benign tumors. By targeting the signature molecular pathway, we investigated the therapeutic effect of ascorbic acid on PCPGs using in vitro and in vivo models. RESULTS: By investigating PCPG cells with low SDHB levels, we show that pseudohypoxia resulted in elevated expression of iron transport proteins, including transferrin (TF), transferrin receptor 2 (TFR2), and the divalent metal transporter 1 (SLC11A2; DMT1), leading to iron accumulation. This iron overload contributed to elevated oxidative stress. Ascorbic acid at pharmacologic concentrations disrupted redox homeostasis, inducing DNA oxidative damage and cell apoptosis in PCPG cells with low SDHB levels. Moreover, through a preclinical animal model with PCPG allografts, we demonstrated that pharmacologic ascorbic acid suppressed SDHB-low metastatic lesions and prolonged overall survival. CONCLUSIONS: The data here demonstrate that targeting redox homeostasis as a cancer vulnerability with pharmacologic ascorbic acid is a promising therapeutic strategy for SDHB-mutated PCPGs.

A novel injectable thermo-sensitive binary hydrogels system for facilitating endoscopic submucosal dissection procedure.

Background and aims: Making an optimal and lasting submucosal cushion is critical for endoscopic submucosal dissection. The thermo-sensitive binary hydrogels system composed of poloxamer 407 and poloxamer 188 might be an excellent submucosal injection solution considering the unique feature that it remains liquid at room temperature and becomes gelatinous after being injected in the submucosa of the digestive tract. The present study focuses on preparing the thermo-sensitive binary hydrogels system and testing its capacity in mucosal lifting and its role in the endoscopic submucosal dissection procedure. Methods: Various concentrations of poloxamer 407 and poloxamer 188 were added to normal saline. The gelation temperature viscosity of the thermo-sensitive binary hydrogels system was measured to choose the best formula. The thermo-sensitive binary hydrogels system and normal saline were first compared in extracted porcine stomach. For in vivo study, the thermo-sensitive binary hydrogels system and normal saline were compared for facilitating the endoscopic submucosal dissection procedure. Results: Among the 46 kinds of thermo-sensitive binary hydrogels system, gelation temperatures of the thermo-sensitive binary hydrogels system I (poloxamer 407/poloxamer 188, 17%/0.5%, w/w) and the thermo-sensitive binary hydrogels system II (poloxamer 407/poloxamer 188, 18%/2%, w/w) were among the ideal range of gelation temperature. The injecting pressure in vitro study of thermo-sensitive binary hydrogels system II was significantly higher than that of thermo-sensitive binary hydrogels system I and normal saline (p < 0.001). Sixteen gastric endoscopic submucosal dissection procedures were performed in a porcine model. The initial volume of normal saline injection (13.88 ± 3.91 ml vs 5.88 ± 3.44 ml, p = 0.001) was significantly larger than the thermo-sensitive binary hydrogels system group. The postoperative wound showed a significant difference in the two groups (p = 0.023) indicating that the thermo-sensitive binary hydrogels system can create a cleaner wound. Conclusions: Considering the gelation temperature, viscosity, injection pressure, and the height of the mucosal elevation, the thermo-sensitive binary hydrogels system I was the better submucosal injection solution.

Submucosal tunnel endoscopic resection for extraluminal tumors: a novel endoscopic method for en bloc resection of predominant extraluminal growing subepithelial tumors or extra-gastrointestinal tumors (with videos).

BACKGROUND AND AIMS: The management of subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors can be challenging and traditionally requires a surgical resection that is not only invasive but may carry a significant risk of morbidity and mortality. We aimed to assess the feasibility, safety, and efficacy of a novel endoscopic technique termed submucosal tunnel endoscopic resection for extraluminal tumors (STER-ET). METHODS: We prospectively enrolled patients who underwent STER-ET for GI subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors located at the level of cardia or the proximal part of the lesser curvature of the stomach seen on cross-sectional imaging between January 2016 and March 2017. RESULTS: Eight patients underwent STER-ET. The mean (± standard deviation) tumor size was 2.8 ± 0.6 cm and 2.3 ± 0.8 cm in longest and shortest dimension, respectively. The average procedure time was 67 ± 4.4 minutes. The rates of curative en bloc resection and en bloc retrieval was 100% and 87.5%, respectively. On final histology, 6 tumors were GI stromal tumors, 1 was a schwannoma, and 1 was a foregut cyst. Five patients had capnoperitoneum during the procedure and required abdominal decompression. One patient had a small mucosotomy successfully treated with a hemostatic clip. There were no major adverse events or deaths. The median length of hospital stay was 3 days. There was no residual tumor on surveillance imaging after a mean follow-up period of 10.0 ± 2.1 months. CONCLUSIONS: STER-ET is a novel technique that appears to be safe and effective in achieving a curative resection for GI subepithelial tumors with a predominantly extraluminal growth pattern or extraluminal tumors in a selected group of patients. However, larger studies are required to validate our finding.

Thoracic CT after peroral endoscopic myotomy for the treatment of achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a promising new endoscopic method for the treatment of achalasia. OBJECTIVE: The aim of this study was to analyze the value of routine postoperative CT of the chest to detect POEM-associated adverse events. DESIGN: Single-center, retrospective study. SETTING: Tertiary care center. PATIENTS AND INTERVENTIONS: Between August 2010 and July 2012, 428 patients underwent POEM. Three hundred postprocedure CT POEM patients were retrospectively analyzed and findings correlated with clinical outcome and management. MAIN OUTCOME MEASUREMENTS: The frequency of postoperative pathological CT scan findings after POEM and the rate of interventions required for adverse event management. RESULTS: The main CT findings could be divided into frequent and reversible sequelae of POEM, pneumomediastinum (48%), pneumoperitoneum (37%), and subcutaneous emphysema (28%), and into potential adverse events such as pneumothorax (17%), pleural effusion (66%), pneumonitis (52%), and focal atelectasis (21%). Only 17 of 50 patients with pneumothorax (5.6% of all patients) and 2 of 200 patients with pleural effusion (0.7% of all patients) required interventional treatment based on clinical symptoms. In 1 patient, a hematoma was observed on a CT scan before any clinical manifestation occurred. Increasing age and the use of air instead of CO2 were associated with an increased rate of pneumothorax (P = .031; 95% confidence interval, 1.002-1.049 and P < .001; 95% confidence interval, 0.012-0.157, respectively). LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Routine chest CT scan for achalasia patients undergoing POEM is probably not warranted because of the high rate of minor and clinically irrelevant findings. The use of CO2 is obligatory to reduce related adverse events.

Peroral endoscopic myotomy for idiopathic achalasia: randomized comparison of water-jet assisted versus conventional dissection technique.

BACKGROUND: Peroral endoscopic myotomy (POEM) has recently been introduced as a promising alternative to laparoscopic Heller myotomy for idiopathic achalasia. Several proposed technical modifications are yet to be tested in randomized trials. OBJECTIVE: The objective of our study was to evaluate efficacy and safety of water-jet (WJ) assisted POEM versus the conventional (C) technique. The clinical trial registration number is NCT01742494. METHODS: A prospective randomized trial was carried out in Zhongshan Hospital, Fudan University (Shanghai, China), in 100 consenting achalasia patients between August 2011 and April 2012. Patients eligible for POEM were randomized to use of either the HybridKnife (WJ group) or the conventional technique using injection and triangle tip knife interchangeably (C group). RESULTS: A total of 100 patients with comparable characteristics between groups were included. Procedure time was significantly shorter for the WJ group (22.9 ± 6.7 vs. 35.9 ± 11.7 min; p < 0.0001), mostly due to less replacement of accessories (2.0 ± 2.4 vs. 19.2 ± 7.6; p < 0.0001). Injection volume was larger in the WJ group (45.3 ± 10.2 vs. 35.2 ± 9.5 ml; p < 0.0001) and was associated with fewer minor bleeding episodes (3.6 ± 1.8 vs. 6.8 ± 5.2; p < 0.0001). No severe complications occurred; one case of cutaneous emphysema occurred in the WJ group, and four cases occurred in the C group (p = 0.17), three cases of pneumonia were encountered in the C group and none in the WJ group (p = 0.24). Treatment success (Eckardt score ≤3) was achieved in 96.5 % of patients, with no significant differences between groups. CONCLUSIONS: The use of the HybridKnife leads to a significant decrease in POEM procedure time and facilitates reinjection, possibly contributing to a lower rate of minor intra-procedural bleeding.

[Effects of peroral endoscopic myotomy on esophageal dynamics in patients with esophageal achalasia].

OBJECTIVE: To investigate the effects of peroral endoscopic myotomy(POEM) on esophageal dynamics in patients with esophageal achalasia. METHODS: From September 2011 to November 2011, 20 cases with esophageal achalasia received POEM at the Endoscopic Center in the Zhongshan Hospital of Fudan University. Pre-operation esophageal dynamics of all the patients were evaluated by high resolution manometry(HRM) system and 3 days after operation the test was repeated. Lower esophagus sphincter resting pressure(LESP), 4-second integrated relaxation pressure(4sIRP), lower esophagus sphincter relax rate(LESRR), lower esophagus sphincter length(LESL), and esophageal manometry were analyzed. RESULTS: After POEM, LESP decreased from(29.1±17.0) mm Hg to(14.6±4.9) mm Hg, and decrease rate was 49.8%(P<0.01). However, the decreases in LESRR and LESL were not statistically significant(P>0.05). Esophageal peristaltic contraction was absent in all the 20 patients preoperatively. After POEM, changes in the esophageal contraction were seen in 7 patients, and peristalsis was noticed but was below normal level. There were no significant changes in peristalsis in the remaining 13 patients. CONCLUSION: POEM can significantly reduce LESP and 4sIRP in patients with achalasia, but can not affect the contraction of the esophagus.

[A pilot study of closure of gastric full-thickness defect with metallic clips in a rabbit model].

OBJECTIVE: To evaluate the feasibility, efficacy, and safety of metallic clips for closure of full-thickness defects in the stomach wall. METHODS: Forty-eight rabbits were randomly divided into 4 groups with 12 in each group using random digits table. A 2 cm×2 cm full-thickness defect was created in the gastric body. No closure was performed in the first group; in the second group, mucosa closure with metallic clips; the third group, closure of full-thickness gastric tissue with metallic clip; the fourth group closure with 3-0 silk suture. After operation the animals were sacrificed at the third day and the seventh day. Wound healing was evaluated. Bursting pressure was recorded. HE and Masson staining was performed to inspect wound inflammation and tissue fibrosis situation. RESULTS: After operation all the animals in the first group died within 34 hours, while those in other groups survived. No intraperitoneal bleeding or infection were seen in the survived animals. General observation showed that the metallic closure group caused less intraperitoneal adhesions. Operative time was shorter in the second and third group compared to the fourth group [(45.8 ± 1.6) min and (42.5 ± 1.5) min vs. (48.0 ± 1.4) min, P<0.05]. The bursting pressure on the third day was lower [(36.9 ± 4.6) mm Hg and (39.8 ± 4.1) mm Hg vs. (50.5 ± 4.2) mm Hg, P<0.05]. There was no significant difference in bursting pressure on the 7th day among the three groups [(95.0 ± 7.9) mm Hg and (97.8 ± 6.8) mm Hg vs. (98.5 ± 7.0) mm Hg, P>0.05]. HE staining revealed that metal closure had a better healing and Masson staining reflected no significant difference in healing at the same time point. CONCLUSIONS: Metal clips closure full-thickness defects in the stomach, regardless in full thickness or mucosa closure, is as safe and effective as suture closure.