COMP promotes pancreatic fibrosis by activating pancreatic stellate cells through CD36-ERK/AKT signaling pathways.

BACKGROUND: Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. METHODS: ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. RESULTS: ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-ß1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. CONCLUSION: In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.

Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

The usefulness of traction-assisted endoscopic papillectomy for ampullary early tumors(with video).

Objective Endoscopic papillectomy(EP) is a minimally invasive treatment for early ampullary tumors. However, the optimal method is unclear. The aim of this study is to explore the efficacy and safety of traction-assisted EP treatments for ampullary early tumors.Methods We retrospective analyzed the patients with ampullary adenoma or early adenocarcinoma underwent endoscopic papillectomy between January 2010 and August 2023, including patient characteristics, lesion size, papilla type, pathological diagnosis and lesion surrounding conditions, en-bloc resection rate, complete resection rate, procedure time, complications, recurrences.Results During the study period, a total of 106 patients with ampullary adenoma or early adenocarcinoma underwent EP. The number of patients in traction group (clip combined with dental floss traction, CDT-EP) and non-traction group (hot snare papillectomy, HSP or endoscopic mucosal resection, EMR) were 45 and 61 respectively. The traction group has a higher en-bloc resection rate and complete resection rate than the non-traction group (92.86% vs. 68.85%, p = 0.003; 90.48% vs. 60.66%, p = 0.001), and the procedure time is slightly shorter[(1.57 ± 1.93)min vs. (1.98 ± 1.76)min, p = 0.039]. The complications and recurrence in the traction group were lower than those in the non-traction group (7.14% vs. 19.72%, p = 0.076; 7.14% vs. 11.78%, p = 0.466), and all complications were successfully treated by endoscopy or conservative medical treatment. There was no statistical difference between the two groups in terms of patient characteristics, papilla type, pathological diagnosis and lesion surrounding conditions (p > 0.050), but there were differences in lesion size[(13 ± 1.09)mm vs. (11 ± 1.65)mm, p = 0.002]. The recurrence rate of the traction group is lower than that of the non-traction group, but the difference is not significant(7.14% vs. 13.11%, p = 0.335), and the non-traction group mainly has early recurrence. Further analysis shows that the size of the lesion, whether en-bloc resection or not, and the method of resection as independent risk factors for incomplete resection (OR = 1.732, p = 0.031; OR = 3.716, p = 0.049; OR = 2.120, p = 0.027).Conclusions CDT- EP, HSP and EMR are all suitable methods for the treatment of ampullary adenoma or early adenocarcinoma. Assisted traction technology can reduce the operation difficulty of large and difficult to expose lesions, thereby improving the efficacy and safety of EP.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Magnetic ring-assisted endoscopic submucosal dissection for gastric lesions with submucosal fibrosis: A preliminary study in beagle model.

BACKGROUND: During endoscopic submucosal dissection (ESD) for gastric lesions with fibrosis, appropriate traction could provide clear submucosal dissection visualization to improve safety and efficiency of procedures. Therefore, the aim of this study was to evaluate the feasibility of magnetic ring-assisted ESD (MRA-ESD) for gastric fibrotic lesions. METHOD: In the eight healthy beagles, 2-3 mL of 50% glucose solution was injected into submucosal layer of the stomach to induce gastric fibrotic lesions. A week after submucosal injection, two endoscopists at different levels performed MRA-ESD or standard ESD (S-ESD) for gastric simulated lesions, respectively. The magnetic traction system consisted of external handheld magnet and internal magnetic ring. The feasibility and procedure outcomes of the magnetic traction system were mainly evaluated. RESULTS: Forty-eight gastric simulated lesions with ulceration were confirmed to have submucosal fibrosis formation by preoperative endoscopic ultrasonography. The magnetic traction system could be easily established, only took 1.57 min, and allowed excellent submucosal visualization. The total procedure time was significantly shorter in the MRA-ESD group than in the S-ESD group for both endoscopists (mean: 46.83 vs. 25.09 min, p < 0.001), and this difference was accentuated in non-skilled endoscopist. There was significant difference between two groups in bleeding and perforation rates. Histological analysis showed the depth of resected specimens was a little deeper around the fibrotic portion in the S-ESD group (p < 0.001). CONCLUSION: The magnetic ring-assisted ESD technique may be an effective and safe treatment for gastric fibrotic lesions and may shorten the endoscopic learning curve for non-skilled endoscopists.

Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells.

BACKGROUND AND AIMS: The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro. METHODS: C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-ß1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs). RESULTS: The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-ß1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs. CONCLUSIONS: Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Case report: Advanced primary squamous cell carcinoma in the periampullary area with upregulation of programmed cell death-ligand 1 expression and response to sintilimab immunotherapy.

Primary squamous cell carcinoma (SCC) of the periampullary area is exceedingly rare. We report a case of a 45-year-old woman who presented with progressive upper abdominal pain and melena. Laboratory testing revealed an elevated level of carcinoembryonic antigen. Esophagogastroduodenoscopy revealed a very large irregular ulcerated tumor in the periampullary area. Contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis, 18 F-fluorodeoxyglucose positron emission tomography/CT, and thin-prep cytologic test excluded metastasis of the primary tumor to the periampullary area from other sites. Immunohistochemistry revealed positive p40 and cytokeratin (CK)5/6, indicating SCC. The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells was upregulated, and the patient responded well to chemotherapy combined with immunotherapy. To the best of our knowledge, this is the first reported case of advanced primary SCC in the periampullary area with high expression of PD-L1.

Experimental Study on Gastric Labeling by Magnetic Detector Combined With Magnetic Bead.

OBJECTIVE: Preoperative labeling of gastric cancer is an important means to determine the surgical margin. At present, there are many commonly used labeling methods. However, which is more accurate and has fewer complications remains to be studied. Through animal experiments, this study explored the feasibility, accuracy, and safety of a magnetic detector combined with magnetic beads for the preoperative labeling of gastric cancer. METHODS: A total of 10 beagle dogs were included in the study. Each dog was randomly labeled with magnetic beads in the gastric body and antrum. After labeling, the magnetic detector was used to explore the gastric serosa surface, and the positioning titanium clip was released at the detected magnetic bead. The main monitoring index was to measure the distance between the labeled magnetic beads and the positioning titanium clamped. The secondary indexes were detection time, magnetic induction intensity, magnetic bead shedding rate, mucosal injury rate, bleeding, and leukocyte and C-reactive protein levels before and 24 hours after the operation. RESULTS: All 10 beagle dogs completed the marking and exploration successfully. The average distance between the magnetic beads and the positioning titanium clip in 20 cases was 5.90±2.36 mm. The average detection time was 1.60±0.69 min, and the average magnetic induction intensity was 3.76±1.11 mT. No magnetic beads were found to fall off, 1 case had a mild mucosal injury, and 2 cases had a small amount of bleeding when releasing the positioning titanium clip. The white blood cells before and 24 hours after the operation were 7.43±0.94(×10 9 /L) versus 7.79±0.67(×10 9 /L) ( P =0.34). The C-reactive protein before and 24 hours after the operation were 5.24±0.97 µg/mL versus 5.95±1.02 µg/mL ( P =0.13). CONCLUSION: A magnetic detector combined with magnetic beads for gastric cancer labeling is feasible, accurate, and safe. It is expected to be further applied in the clinic.

Multiple ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography: a novel method to treat rectal neuroendocrine tumors.

OBJECTIVE: The first choice of treatment for rectal neuroendocrine tumors (R-NETs) 10 mm in size is endoscopic resection, there is still controversy concerning the optimal endoscopic treatment for resecting R-NETs. This study evaluated the efficacy and safety of multiple ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (EMR-MLUS) for R-NETs. METHODS: We retrospectively analyzed the data of 62 patients with R-NETs ≤10 mm in size who underwent EMR-MLUS or ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (EMR-LUS) between May 2019 and April 2022, including tumor characteristics, endoscopic complete resection, pathological complete resection, the procedure time, adverse events, and follow-up were compared between the two groups of patients. RESULTS: Of the 62 patients, 19 underwent EMR-MLUS and 43 underwent EMR-LUS. The endoscopic morphology of lesions was statistically different between group EMR-MLUS and group EMR-LUS ( P = 0.015), and most of them were flat and slightly raised lesions in group EMR-MLUS. Although the pathological complete resection rate was slightly higher in the EMR-MLUS group than in the EMR-LUS group (94.74% vs. 90.70%; P = 0.290), the endoscopic complete resection rate was high in both groups. Involvement of the lateral resection margin was found four cases in the ESMR-LUS group; one case of deep resection margin involvement in the EMR-MLUS group. The mean procedure time was longer in the EMR-MLUS group than in the EMR-LUS group (12.79 ± 1.01 min vs. 11.08 ± 1.89 min; P = 0.041). In group EMR-LUS, there were two cases of immediate bleeding; in group EMR-MLUS, one case of perforation, all of them were successfully treated by endoscopy. No recurrence, progression, or metastasis was found in all patients. CONCLUSION: EMR-MLUS is a safe and effective technique that could be considered when removing small rectal NETs, especially flat and slightly raised lesions.

A prospective, open-labeled, and randomized trial for assessing safety and clinical utility of gastric biopsies during emergency gastroscopy for patients with bleeding gastric ulcers.

OBJECTIVE: There is no consensus on whether a gastroscopic biopsy is necessary during the emergency treatment of gastrointestinal (GI) diseases such as gastric ulcer bleeding. In this study, we examined the clinical utility and safety of an emergency gastroscopic biopsy for the assessment of gastric ulcer bleeding. METHODS: We enrolled 150 patients with a single bleeding gastric ulcer after emergency gastroscopy (EG) from April 2020 to April 2022. The patients were randomly divided into the biopsy and no biopsy groups, and they were followed-up until June 2022 to examine whether recurrent gastric ulcer bleeding had occurred. RESULTS: Re-bleeding occurred in 15 out of 150 (10%) patients. We diagnosed malignancies in 17 (11.3%) patients and validated 14 (9.3%) of them during the initial gastroscopy procedure. Factors that could predict the occurrence of gastric ulcer re-bleeding with biopsy during EG included an absence of ischemic heart disease (odds ratio [OR] = 0.395, confidence interval [CI]: 0.24-0.65, p ≤ .005), renal disease (OR = 1.74, CI: 0.77-1.59, p ≤ .005), and using warfarin or oral anticoagulants (OR = 11.953, CI: 3.494-39.460, p ≤ .005). No significant differences were observed in 60-day bleeding (p = .077) and the duration of hospitalization (p = .700) between the two groups. CONCLUSIONS: Patients undergoing biopsy during EG did not exhibit an increased risk of re-bleeding compared with those who did not undergo a biopsy. An early biopsy facilitates an early pathologic diagnosis, early clinical intervention, safe discharge of low-risk patients, and improved outcomes in high-risk patients.

Usefulness of the combined orthodontic rubber band and clip method for gastric endoscopic submucosal dissection.

BACKGROUND AND AIMS: Effective traction is an important prerequisite for successful endoscopic submucosal dissection (ESD). The combined orthodontic rubber band (ORB) and clip method was effective in colorectal cancer ESD. To date, the method was not reported in gastric ESD. This study aimed to investigate its efficacy and safety for gastric neoplasms ESD. METHODS: We retrospectively analyzed data of 118 patients with gastric neoplasms treated by ESD from November 2020 to April 2022, 43 by ORB-ESD and 75 by the conventional ESD. The primary outcome measure was the ESD procedure time. Clinical data on efficacy and safety were also collected and analyzed. Propensity score matching (PSM) matched the patients in both groups. RESULTS: PSM successfully matched 31 pairs of patients. The ORB-ESD operation time was shorter (median [interquartile range], 35 [30-48] vs. 49 [40-70] min, P < 0.001) and dissection speed was higher (median [interquartile range], 22.6 [14.4-29.3] vs. 13.5 [9.6-17.9] mm2/min, P < 0.001) than in the conventional ESD. The groups were similar in muscular injury rate, frequency and time of use of thermal hemostatic forceps, postoperative adverse events, en bloc resection, and R0 resection rate (P > 0.05). CONCLUSIONS: Compared to the conventional ESD, ORB-ESD significantly reduced the procedure time and increased the dissection speed, proving beneficial to gastric ESD.

Antimicrobial prophylaxis in patients undergoing endoscopic mucosal resection for 10- to 20-mm colorectal polyps: A randomized prospective study.

BACKGROUND AND PURPOSE: Endoscopic mucosal resection (EMR) is frequently used for the removal of colorectal neoplasms. However, the use of prophylactic antibiotics in patients undergoing EMR is debatable. The aim of this randomized controlled trial was to assess whether antimicrobial prophylaxis is crucial in the perioperative period of EMR, especially for 10- to 20-mm lesions in this setting. METHODS: Two hundred and sixty-four patients were randomized equally into 2 groups, the antibiotic (cefixime) group and the control group. The occurrence of adverse events was examined at 1 to 3 days after EMR. Plasma levels of inflammatory markers were analyzed at pre-operation, 1 day post-operation and 3 days post-operation. Blood samples collected at 1 day post-operation were used for culture. RESULTS: A total of 264 and 268 polyps were removed by EMR in the antibiotic group and the control group, respectively. There were 5 cases of fever, with 2 in the antibiotic group and 3 in the control group. In the antibiotic group, 12 patients had abdominal pain and 10 suffered bleeding, whereas in the control group, abdominal pain and bleeding were observed in 10 and 11 patients, respectively. There were no significant differences in the proportion of patients with fever or the incidences of postoperative complications between the groups. No significant differences between the groups were reported in plasma levels of white blood cell count, erythrocyte sedimentation rate, C-reactive protein or procalcitonin at pre-operation or post-operation. No patients provided positive blood cultures. CONCLUSIONS: The use the prophylactic antibiotics for EMR procedures in the perioperative period is no longer required when the lesions are 10 to 20 mm in size.

Splenic infarction during acute falciparum malaria: A case report.

Splenomegaly is common in malaria, but splenic infarction is a rare complication of malaria. We report a case of a patient with Plasmodium falciparum infection who developed abdominal pain, reappearance of fever, elevated D-dimer during treatment, and abdominal CT confirmed splenic infarction. The abdominal pain was relieved and the fever subsided by analgesic and anticoagulant therapy. Six months later, abdominal CT showed splenic recovery. As a result, splenic infarction should be considered when a patient with malaria developed abdominal pain, reappearance of fever and elevated blood D-dimer during treatment. In the absence of surgical indications, conservative medical treatment is effective.

Linked color imaging-based endoscopic grading of gastric intestinal metaplasia and histological gastritis staging in the assessment of gastric cancer risk.

OBJECTIVE: To evaluate the value and compare the effectiveness of linked color imaging-based endoscopic grading of gastric intestinal metaplasia (LCI-EGGIM) and operative link on gastric intestinal metaplasia (OLGIM) in risk stratification of early gastric cancer (EGC). METHODS: Eighty-one patients with EGC who underwent endoscopic submucosal dissection were included. The general data and EGC-related risk factors of all participants were recorded. LCI-EGGIM and OLGIM were used for both groups. RESULTS: The number of patients with LCI-EGGIM score ≥ 5 was significantly higher in the EGC group than in the control group (58.02% vs. 12.35%, p < .001). Furthermore, the number of patients with OLGIM stage III/IV in the EGC group was significantly higher than that in the control group (56.79% vs. 7.41%, p < .001). Multivariate analysis showed that OLGIM stage III/IV (adjusted odds ratio [AOR]: 29.74, 95% CI: 7.49-117.94) and LCI-EGGIM score ≥ 5 (AOR: 12.33, 95% CI: 3.71-41.02) were significantly associated with EGC. There was no significant difference in the area under the receiver operating characteristic curve between LCI-EGGIM and OLGIM in predicting the risk of EGC (0.74 vs. 0.77, p = .1116). CONCLUSION: OLGIM and LCI-EGGIM can be used and have the same value for predicting the risk stratification of EGC in patients with gastric intestinal metaplasia.

Gallbladder-preserving polypectomy for gallbladder polyp by embryonic-natural orifice transumbilical endoscopic surgery with a gastric endoscopy.

BACKGROUND AND AIMS: Cholecystectomy is performed for most gallbladder polyps (GPs). However, cholecystectomy results concerning complications in some patients. For benign GPs, adoption of gallbladder-preserving surgery is worth to recommend. We describe our experiences performing gallbladder-preserving polypectomy for GPs by embryonic-natural orifice transumbilical endoscopic surgery (E-NOTES) with a gastric endoscopy. METHODS: This is a retrospective study of patients with GPs who underwent gallbladder-preserving polypectomy by E-NOTES with a gastric endoscopy from April 2018 to September 2019 in our hospital. The operative time, intraoperative hemorrhage, intraoperative and postoperative complications, gallbladder emptying function were obtained and analyzed. RESULTS: The procedure was performed successfully in all 12 patients with 5 cases of single polyp and 7 cases of multiple polyps. The range of GPs size was 2 mm to 15 mm. The mean operation time was (95.33 ± 23.08) minutes (55-135 min). There were no adverse events including heavy bleeding, mortality and conversion to open surgery during operation. All patients were discharged in 4-5 days after surgery without postoperative complications such as delayed bleeding, fever, peritonitis, intra-abdominal abscess and abdominal wall incisional hernia. All patients were followed up at 1, 3, 6, and 12 months postoperation who had almost no visible incision on the umbilical region, no recurrent GPs. The gallbladder emptying function decreased one month after surgery, and gradually improved 3, 6 and 12 months after surgery. CONCLUSION: E-NOTES gallbladder-preserving polypectomy is a safe and effective option for patients with GPs and is close to scar-free surgery which can be performed in routine clinical practice.

Orthodontic Rubber Band-Assisted Endoscopic Submucosal Dissection: An Efficient Method for Treating Superficial Colorectal Tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a complex operation. Effective traction is crucial. We have successfully used an orthodontic rubber band (ORB) combined with the clip traction method to assist ESD (ORB-ESD). The aim of this retrospective study is to describe the method and to compare the efficacy and safety of ORB-ESD versus conventional ESD in the treatment of superficial colorectal tumors. METHODS: We retrospectively analyzed the data of patients with superficial colorectal tumor (with diameter ≥ 20 mm) who received either ORB-ESD (n = 34) or conventional ESD (n = 90) between January 2019 and September 2020. Propensity score matching (PSM) was used to match the clinical data of 31 pairs of patients in each group. RESULTS: Operation time was significantly shorter for ORB-ESD than for conventional ESD (34.5 minutes vs. 56 minutes, P ≤ 0.001). In the propensity-matched cohorts, the operation time remained significantly shorter in the ORB-ESD patients (35 minutes vs. 50 minutes, P = 0.001). Postoperative adverse events, en bloc resection rate, and R0 resection rate were comparable between the two groups (P > 0.05), both before and after propensity score matching. In the ORB subgroup analysis, the trainee and expert ESD operation times were similar (37 (26-53) vs. 33.5 (26-37) minutes, respectively; P = 0.274). CONCLUSION: ORB-ESD appears to be an effective technique for ESD of colorectal cancer. Our findings need to be confirmed in large prospective multicenter studies.

Efficacy and safety of ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography for treatment of rectal neuroendocrine tumors.

OBJECTIVE: Rectal neuroendocrine tumors (R-NETs) usually invade the submucosa, and so complete resection is difficult. The treatment of choice for R-NETs ≤10 mm in size is endoscopic resection, but there is still controversy concerning the best endoscopic method. This study evaluated the efficacy and safety of ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (ESMR-LUS) for treatment of R-NETs. METHODS: We retrospectively analyzed the data of 101 patients with R-NETs ≤10 mm in size who underwent ESMR-LUS (n = 48) or conventional ligation-assisted endoscopic submucosal resection (ESMR-L; n = 53) between May 2019 and September 2021 at the 900th Hospital of Joint Logistics Support Force. Complete resection rate, pathological complete resection rate, procedure time, and adverse events were compared between the two groups of patients. RESULTS: The endoscopic complete resection rate was slightly higher in the ESMR-LUS group than in the ESMR-L group (100 vs. 96.2%, p = .496). The pathological complete resection rate was also slightly higher in the ESMR-LUS group (97.9 vs. 88.7%, p = .152), these findings, though statistically non-significant, have practical clinical significance. Margin involvement was less common in ESMR-LUS patients than in ESMR-L patients (1 vs. 6). Involvement of the lateral resection margin was found one patient in the ESMR-LUS group versus two patients in the ESMR-L group, and deep resection margin involvement in no patient in the ESMR-LUS group versus four patients in the ESMR-L group. Mean procedure time was longer in the ESMR-LUS group than in the ESMR-L group (11.08 ± 1.89 min vs. 9.38 ± 2.09 min, p = .061). Immediate bleeding occurred in two patients in the ESMR-LUS group vs. seven patients in the ESMR-L group. Two patients in the ESMR-L group also suffered perforation; both patients were successfully treated by endoscopy. CONCLUSIONS: ESMR-LUS appears to be a safe and effective technique for removal of small rectal NETs confined to the submucosal layer without metastasis. Further studies are warranted to compare the efficacy and safety of different methods.

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

Puerarin Ameliorates Caerulein-Induced Chronic Pancreatitis via Inhibition of MAPK Signaling Pathway.

Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP), and pancreatic stellate cells (PSCs) are considered to be the key cells. Puerarin is the most important flavonoid active component in Chinese herb Radix Puerariae, and it exhibited anti-fibrotic effect in various fibrous diseases recently. However, the impact and molecular mechanism of puerarin on CP and pancreatic fibrosis remain unknown. This study systematically investigated the effect of puerarin on CP and pancreatic fibrosis in vivo and in vitro. H&E staining, Sirius Red staining, qRT-PCR and Western blotting analysis of fibrosis and inflammation related genes of pancreatic tissues showed that puerarin notably ameliorated pancreatic atrophy, inflammation and fibrosis in a model of caerulein-induced murine CP. Western blotting analysis of pancreatic tissues showed the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) significantly increased after modeling of cerulein, while puerarin could inhibit their phosphorylation levels to a certain extent. We found that puerarin exerted a marked inhibition on the proliferation, migration and activation of PSCs, determined by CCK-8 assay, transwell migration assay, scratch wound-healing assay and expression levels of α-SMA, Fibronectin, Col1α1 and GFAP. Western blotting result demonstrated that puerarin markedly inhibited the phosphorylation of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) of PSCs in a dose-dependent manner whether or not stimulated by platelet-activating factor. In conclusion, the present study showed that puerarin could be a potential therapeutic candidate in the treatment of CP, and the MAPK pathway might be its important target.