Efficacy and safety of piecemeal submucosal tunneling endoscopic resection for giant esophageal leiomyoma.

BACKGROUND AND AIMS: Giant esophageal leiomyoma usually requires a thoracotomy or thoracoscopic surgery, which is more invasive than an endoscopic treatment. The purpose of this study is to evaluate the efficacy and safety of piecemeal submucosal tunneling endoscopic resection (P-STER) for giant leiomyoma originating from the muscularis propria (MP) layer of the esophagus. METHODS: This is a retrospective study. Patients with giant esophageal leiomyoma (transverse diameter ≥ 3 cm) who underwent P-STER were enrolled from November 2012 to May 2023. Clinical data and results were investigated. RESULTS: A total of 16 patients were enrolled for analysis. The lesion mean transverse diameter and longitudinal diameter were 4.22 ± 1.20 cm and 6.20 ± 1.57 cm, respectively. Our mean operation time was 195.38 ± 84.99 min. The mean number of piecemeal resected was 4.31 ± 2.36. An adverse event noted was an esophageal fistula that occurred in one case (6.25%) and was treated conservatively. The mean length of hospital stay was around 11.81 ± 7.30 days. The mean total hospitalization cost was U.S. dollars (USD) $5976.50 ± 2866.39. No recurrence or metastasis was found during the follow-up period. CONCLUSIONS: P-STER can be an effective and safe treatment for giant leiomyoma originating from the MP layer of the esophagus.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

Development and Validation of an Artificial Intelligence Model for Small Bowel Capsule Endoscopy Video Review.

Importance: Reading small bowel capsule endoscopy (SBCE) videos is a tedious task for clinicians, and a new method should be applied to solve the situation. Objectives: To develop and evaluate the performance of a convolutional neural network algorithm for SBCE video review in real-life clinical care. Design, Setting, and Participants: In this multicenter, retrospective diagnostic study, a deep learning neural network (SmartScan) was trained and validated for the SBCE video review. A total of 2927 SBCE examinations from 29 medical centers were used to train SmartScan to detect 17 types of CE structured terminology (CEST) findings from January 1, 2019, to June 30, 2020. SmartScan was later validated with conventional reading (CR) and SmartScan-assisted reading (SSAR) in 2898 SBCE examinations collected from 22 medical centers. Data analysis was performed from January 25 to December 31, 2021. Exposure: An artificial intelligence-based tool for interpreting clinical images of SBCE. Main Outcomes and Measures: The detection rate and efficiency of CEST findings detected by SSAR and CR were compared. Results: A total of 5825 SBCE examinations were retrospectively collected; 2898 examinations (1765 male participants [60.9%]; mean [SD] age, 49.8 [15.5] years) were included in the validation phase. From a total of 6084 CEST-classified SB findings, SSAR detected 5834 findings (95.9%; 95% CI, 95.4%-96.4%), significantly higher than CR, which detected 4630 findings (76.1%; 95% CI, 75.0%-77.2%). SmartScan-assisted reading achieved a higher per-patient detection rate (79.3% [2298 of 2898]) for CEST findings compared with CR (70.7% [2048 of 2298]; 95% CI, 69.0%-72.3%). With SSAR, the mean (SD) number of images (per SBCE video) requiring review was reduced to 779.2 (337.2) compared with 27 910.8 (12 882.9) with CR, for a mean (SD) reduction rate of 96.1% (4.3%). The mean (SD) reading time with SSAR was shortened to 5.4 (1.5) minutes compared with CR (51.4 [11.6] minutes), for a mean (SD) reduction rate of 89.3% (3.1%). Conclusions and Relevance: This study suggests that a convolutional neural network-based algorithm is associated with an increased detection rate of SBCE findings and reduced SBCE video reading time.

Simultaneous imaging of hypochlorous acid and nitric oxide in live cells based on a dual-channel fluorescent probe.

Both reactive oxygen species (ROS) and reactive nitrogen species (RNS) are inevitably produced during normal human metabolism. Various ROS and RNS together form tangled networks that play important roles in many physiological and pathological processes. Here we used 1,8-naphthalene diamine as a reactive group to develop a fluorescent probe, N-[2-(6-phenylethynyl)quinolinylmethyl]-1,8-diamino naphthalene (QBN), for HOCl and NO. QBN showed a "turn-on" fluorescent response at 464 nm to HOCl in the range of 0-75 µM with rapid responding time (10 s) and detection limit (0.11 ± 0.03 µM). Furthermore, a "turn-on" fluorescent responses at 512 nm to NO in the range of 0-40 µM with responding time (20 s) and detection limit (25.7 ± 3.4 nM) was found. The response mechanisms of QBN to HOCl and NO were discussed based on mass analysis of the different products. The dual-channel probe was then successfully applied for simultaneous imaging of both exogenous and endogenous HOCl and NO in live cells.

Fully automated magnetically controlled capsule endoscopy for examination of the stomach and small bowel: a prospective, feasibility, two-centre study.

BACKGROUND: The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. METHODS: We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18-80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. FINDINGS: Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0-55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3-100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45-99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00-20·00), compared with 5·21 min (2·00; 5·18, 3·68-6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. INTERPRETATION: The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. FUNDING: Chinese National Key Research and Development Program.

Novel endoscopic treatment strategy for early esophageal cancer in cirrhotic patients with esophageal varices.

The safety and efficacy of endoscopic submucosal dissection (ESD) and radiofrequency ablation for early esophageal cancer (EEC) in cirrhotic patients has not been thoroughly investigated to date. The present study aimed to establish a standard treatment strategy for EEC in cirrhotic patients with esophageal varices. Six cirrhotic patients with early flat-type EECs (high-grade intraepithelial neoplasia) on or adjacent to esophageal varices were enrolled. Esophageal varix ligation (EVL) or transjugular intrahepatic portosystemic shunt (TIPS) were used for the initial management of esophageal varices. Follow-up endoscopy was performed two months following the initial procedure. The mean longitudinal length of the lesions was 4.3 cm (range, 2-6 cm). The average procedure time was 72.8 min (range, 34-135 min) and the average longitudinal length of the resected specimens was 45.6 mm (range, 30-90 mm). One case had a tumor-positive lateral margin with lymphovascular infiltration. Both complete and curative resection rates were 80% (4/5 lesions). Large intraoperative bleeding was detected in patients undergoing EVL compared with TIPS prior to the ESD procedure. No severe complications or mortality-associated events, including massive postoperative bleeding, perforation or hepatic failure, were observed. No recurrence and metastasis were observed during the follow-up period. The current study suggested a novel treatment strategy for EECs complicated by esophageal varices in cirrhosis with good treatment results, no neoplastic progression and an acceptable adverse event profile.

Regulation of the master regulator FOXM1 in cancer.

FOXM1 (forkhead box protein M1) is a critical proliferation-associated transcription factor that is widely spatiotemporally expressed during the cell cycle. It is closely involved with the processes of cell proliferation, self-renewal, and tumorigenesis. In most human cancers, FOXM1 is overexpressed, and this indicates a poor prognosis for cancer patients. FOXM1 maintains cancer hallmarks by regulating the expression of target genes at the transcriptional level. Due to its potential role as molecular target in cancer therapy, FOXM1 was named the Molecule of the Year in 2010. However, the mechanism of FOXM1 dysregulation remains indistinct. A comprehensive understanding of FOXM1 regulation will provide novel insight for cancer and other diseases in which FOXM1 plays a major role. Here, we summarize the transcriptional regulation, post-transcriptional regulation and post-translational modifications of FOXM1, which will provide extremely important implications for novel strategies targeting FOXM1.

A Quninolylthiazole Derivatives as an ICT-Based Fluorescent Probe of Hg(II) and its Application in Ratiometric Imaging in Live HeLa Cells.

As a structural analogue of pyridylthiazole, 2-(2-benzothiazoyl)-phenylethynylquinoline (QBT) was designed as a fluorescent probe for Hg(II) based on an intramolecular charge transfer (ICT) mechanism. The compound was synthesized in three steps starting from 6-bromo-2-methylquinoline, with moderate yield. Corresponding studies on the optical properties of QBT indicate that changes in the fluorescence ratio of QBT in response to Hg(II) could be quantified based on dual-emission changes. More specifically, the emission spectrum of QBT before and after interactions with Hg(II) exhibited a remarkable red shift of about 120 nm, which is rarely reported in ICT-based fluorescent sensors. Finally, QBT was applied in the two-channel imaging of Hg(II) in live HeLa cells.

Application of clip traction in endoscopic submucosal dissection to the treatment of early esophageal carcinoma and precancerous lesions.

BACKGROUND AND AIM: It is usually difficult to obtain a good view of the dissection plane during esophageal endoscopic submucosal dissection (ESD). Therefore, the aim of this study was to investigate the efficacy and safety of clip traction in ESD for the treatment of early esophageal carcinoma (EEC) or precancerous lesions. METHODS: This is a case-matched comparative study. We selected 100 EEC patients who had undergone ESD. Fifty cases underwent ESD without clip traction (non-clip group), and 50 cases underwent ESD with clip traction (clip group). The patient-related variables, dissection time, data regarding muscularis propria injury, etc. were statistically analyzed. RESULTS: ESD was successful in all cases without complication. There were no significant differences between the two groups with respect to age, gender, the longitudinal diameter of the lesions, etc. Wide visual field exposure of the submucosal tissue below the lesion was obtained by applying clip traction. The dissection time of ESD was shorter in the clip group than in the non-clip group [22.02 (6.77) min vs 26.48 (12.56); P = 0.018] when the extent of lesion was less than half of the circumference of the esophagus; otherwise, there was no difference between the two groups (P = 0.252). Moreover, the muscularis propria injuries in the clip group were obviously less than the non-clip group (10 vs 30 %, P = 0.007). CONCLUSION: Clip traction can decrease the rate of muscularis propria injury and shorten the dissection time. It is recommended as a safe and effective auxiliary procedure for the treatment of esophageal ESD.

Endoscopic submucosal dissection for superficial esophageal cancer with near-circumferential lesions: our experience with 40 patients.

BACKGROUND: Nowadays, there are few reports indicating whether early esophageal cancers (EsC) with near-circumferential lesions are still appropriate for the endoscopic submucosal dissection (ESD) procedure. METHODS: Between November 2009 and December 2013, a total of 40 patients with early esophageal cancers were treated with ESD. The characteristics of the patients, the ESD procedure variables, the rates of en bloc resection, and the major complications were evaluated. The outcomes listed were reliably followed up, and postoperative endoscopic balloon dilation was conducted to treat the esophageal strictures. RESULTS: A total of 40 patients with superficial esophageal cancers were treated with ESD procedure. The extent of the lesions as a proportion of the whole circumference of the esophageal lumen ranged from three-quarters (18/40) to four-fifths (4/40) and complete circumference (18/40). The median longitudinal diameter of the lesions was 50 mm. The median procedure time was 92.5 min (range, 70-125 min). The en bloc resection rate was 100 % (40/40). Immediate bleeding, perforation, and postoperative stenosis were noted in 7.5 (3/40), 7.5 (3/40), and 45 % (18/40) of the patients. The median number of endoscopic balloon dilations (EBDs) was 4 (range 1-14). Additional surgical treatment was performed in 2 cases, and local recurrence was detected in 1 patient (2.5 %). 2 patients (5 %) died of EsC 3 months after ESD. CONCLUSIONS: These data will greatly expand the criteria for the use of ESD in esophageal cancer and increase the number of patients eligible for endoscopic treatment and the acceptance of the ESD procedure.

Small Bowel Endoscopy Diagnostic Yield and Reasons of Obscure GI Bleeding in Chinese Patients.

Aim. To investigate the diagnostic yield and etiologies of patients with obscure gastrointestinal bleeding (OGIB) using capsule endoscopy (CE) or double-balloon enteroscopy (DBE). Method. We studied the data of 532 consecutive patients with OGIB that were referred to Xinqiao Hospital in Chongqing from December 2005 to January 2012. A lesion that was believed to be the source of the bleeding (ulceration, mass lesion, vascular lesion, visible blood, inflammation, or others) was considered to be a positive finding. We analyzed the diagnostic yield of CE and SBE and the etiologies of OGIB. Result. CE and SBE have similar diagnostic yields, at 71.9% (196/231) and 71.8% (251/304), respectively. The most common etiology was erosions/ulceration (27.1%) followed by mass lesion (19.4%) and angiodysplastic/vascular lesions (13.9%). By stratified analysis, we found that erosions/ulceration (27.1%) was the most common etiology for the 21-40-year age group. Mass lesion was the most common etiology in the 41-60-year age group. However, in the >60 years age group, angiodysplastic/vascular lesions were significantly increased compared with the other groups, even though erosions/ulceration was most common. Conclusion. In this study, we found that CE and SBE have similar diagnostic yields and erosions/ulceration was the most common reason for OGIB, followed by mass lesion and angiodysplasias.

Diepitope multiple antigen peptide of hTERT trigger stronger anti-tumor immune responses in vitro.

Rapid advances in immune system knowledge have led to the exploration of immunologic approaches for eliminating tumor cells. Human telomerase reverse transcriptase (hTERT) is considered to be an ideal universal target for novel immunotherapies against cancers. Thus far, studies of effective antitumor immunotherapies have focused on the quantity and quality of the effector function of the CD8 compartment. However, increasing evidence has demonstrated that CD4+ T cells play important roles in generating and maintaining antitumor immune responses in animal models. The aim of this work was to verify whether diepitope multiple antigen peptides (MAPs) that were composed of the cytotoxic T lymphocyte (CTL) epitope of hTERT and the T-helper epitope of hTERT could improve upon the immunogenicity of a monoepitope MAP of hTERT. Dendritic cells (DCs) pulsed with diepitope MAPs composed of the CTL epitope hTERT-540 and the T-helper epitope hTERT-766 were used to evaluate immune responses against various tumor cells. A standard in vitro 4-h 5¹Cr-release assay was employed in this study. The results demonstrated that CTLs activated by the diepitope MAP that consisted of hTERT-540 and hTERT-766 could cause 8.56% more lysis than CTLs activated by the monoepitope MAP containing hTERT-540. Moreover, the activated CTLs could kill neither hTERT-negative tumor cells, such as U2OS cells, nor HLA-A2 negative cells, such as HepG2 cells. Our results indicate that diepitope MAPs that are generated from hTERT can be exploited for cancer immunotherapy.

CpG oligodeoxynucleotides discriminately enhance binding capacity of human naïve B cells to Hepatitis B virus epitopes.

CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen-presenting cells function of human naïve B cells. In this study, we aim to define the effect of CpG ODNs on the binding capacity of human naïve B cells for different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were selected to incubate with CpG ODN-primed human naïve B cells. Binding capacity for each epitope and expression of CD80, CD86, class I major histocompatibility complex (MHC), and class II MHC of naïve B cells was tested, respectively, by flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of human naïve B cells for HBV epitopes (p < 0.01), and induced markedly higher expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of CpG-treated naive B cells for each epitope was significantly different. In all the 3 subjects, CpG ODN 2216-primed naïve B cells showed the highest binding ability for Env172-180 compared with the other epitopes with a high expression of co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively enhance the binding capacity of human naïve B cells for HBV epitopes. These results suggest new strategies for development of vaccine design.

[Sulfur dioxide-induced liver pathology].

OBJECTIVE: To investigate effects of short-term sulfur dioxide inhalation to the liver. METHODS: Haematoxylin and eosin staining (HE) and transmission electron microscopy (TEM) were used to study the pathologic changes in mice liver after sulfur dioxide (SO(2)) inhalation. RESULTS: Exposure to 56 mg/m(3), 112 mg/m(3) 168 mg/m(3) SO(2) caused increasingly severe liver injuries, as detected by HE staining and TEM. The morphologic changes included spotty necrosis with lymphocyte, monocyte, and neutrophil infiltration, fatty degeneration of hepatocytes with dilatation of rough endoplasmic reticulum and dissociation of ribosomes, as well as degeneration of mitochondria and karyorrhexis. CONCLUSION: SO(2) inhalation can cause marked liver injury in experimental settings.