Transumbilical endoscopic surgery in the diagnosis of ascites of unknown origin.

OBJECTIVE: To explore whether transumbilical endoscopic surgery (TUES) can effectively and safely elucidate the causes of ascites of unknown origin.
 Methods: A total of 23 consecutive patients with ascites of unknown origin who undertook TUES procedures in the Department of Gastroenterology of The Third Xiangya Hospital of Central South University between January 2014 and January 2016 were retrospectively investigated. Clinical manifestations, laboratory examinations and findings from radiological examinations and endoscopic investigations were noted before the procedure. Conditions of the abdominal cavity under endoscope, final diagnosis and outcome of patients were carefully recorded.
 Results: TUES procedure was successfully performed in all 23 patients with an operation time of (58.2±13.9) min. Twenty-two patients were undertaken biopsy on the nodules or masses that found in the abdominal cavity. Definite diagnoses were established in the overwhelming majority of patients (22/23). The most common causes of ascites for the 23 cases was tuberculosis (8 cases), followed by peritoneal carcinomatosis (6 cases), and pseudomyxoma peritonei (5 cases). Operation-related complications, such as postoperative bleeding, perforation, peritonitis, intraabdominal chronic abscesses, were not observed, except one case showed a transient moderate fever in 24 hours after operation. No mortality related to TUES occurred. We concluded that TUES was a feasible, economic and minimally invasive approach to access the peritoneal cavity.
 Conclusion: TUES combinated with biopsy can effectively elucidate the causes of ascites of unknown origin.

Correction to: Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

The HTML version of this article was updated to indicate that the copyright is with The Author(s).

Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

BACKGROUND: To compare the diagnostic yield and safety of 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in the diagnosis of pancreatic solid lesions. METHODS: Between April 2014 and September 2015, 36 patients with pancreatic solid lesions were included for endoscopic ultrasound test. Patients were randomly divided into two groups: EUS-FNA (n = 18) and EUS-FNB (n = 18). Each nidus was punctured three times (15 ~ 20 insertions for each puncture) with a 22G needle. The core specimens were analyzed, and the diagnostic yields of FNA and FNB were evaluated. RESULTS: The procedure success rate was 100% with no complications. Cytological and histological examinations found that the diagnostic yield of FNB and FNA were both 83.3%. To get a definitive diagnosis, FNB needed fewer punctures than FNA (1.11 vs. 1.83; P  <  0.05). CONCLUSIONS: 22G EUS-FNB is a safe and effective way to diagnose pancreatic solid lesions. FNB required a lower number of needle passes to achieve a diagnosis compared with FNA.

Incomplete ileus and hemafecia as the presenting features of multi-organ involved primary systemic AL amyloidosis: a rare case report.

BACKGROUND: AL Amyloidosis is known to be a systemic disease affecting multiple organs and tissue while it's rare that patients present with gastrointestinal symptoms at first and later develop multiple-organ dysfuction. Clinical signs are not specific and the diagnosis is rarely given before performing immunofixation and endoscopy with multiple biopsies. We would like to emphasize the value of precise diagnostic process of AL amyloidosis. CASE PRESENTATION: In this case report, we describe a 56-year-old man who presented with recurrent periumbilical pain for 4 months and gradually worsened over a month. After a series of tests, he was finally diagnosed with primary systemic AL amyloidosis. He was treated with a chemotherapy regimen (Melphalan, dexamethasone and thalidomide) achieving a good clinical response. CONCLUSION: On account of the high misdiagnosis rate, establishing the most precise diagnosis in first time with typing amyloidogenic protein becomes increasingly vital. Although the presenting feature is usually nonspecific, AL amyloidosis ought to be considered when multiple organs are involved in a short period.

Application of clips assisted with foreign body forceps in defect closure after endoscopic full-thickness resection.

BACKGROUND: This study was designed to evaluate the feasibility and efficacy of metallic clips assisted with foreign body forceps closing the gastric wall defect after endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs). METHODS: Eighteen patients with gastric SMTs originated from the muscularis propria were treated by EFR between September 2012 and June 2014. Twelve patients underwent endoscopic closure of the gastric wall defects after EFR with endoloop and metallic clips (endoloop string suture method, ESSM), and six patients with clips and foreign body forceps (clips assisted with foreign body forceps clip method, CFCM). RESULTS: No significant differences existed between the two groups in terms of demographics, clinical characteristics, and the size of the gastric wall defects. The average time spent in closing the gastric wall defects (14.83 ± 1.94 min for the CFCM group and 22.42 ± 5.73 min for the ESSM group) and hospitalization fees of the CFCM group were significantly lower than those of the ESSM group. The average hospitalization time of the two groups had no statistical significance. No single case had surgical intervention or complications, such as gastric bleeding, perforation, peritonitis, or abdominal abscess. CONCLUSION: The CFCM and the ESSM are safe and effective techniques for gastric defect closure after EFR for gastric SMTs. Because of the "chopsticks effect," the CFCM more suitable for the lesions located at the gastric fundus, the greater curvature or anterior wall of the gastric body and gastric antrum.

[Experience in transumbilical endoscopic surgery diagnosis for 3 cases of pseudomyxoma peritonei].

Three patients of pseudomyxoma peritonei who were diagnozed by transumbilical endoscopic surgery (TUES) were reviewed retrospectively from September 2014 to November 2014. Three cases of ascites patients underwent TUES were diagnozed as pseudomyxoma peritonei. All operations were successful. No open surgery or laparoscopic surgery was required. The mean operative time was (45±16) min; the mean intraoperative blood loss was 510 mL; the mean hospital stay time was 3 days. During the follow up of 911 months, no obvious scar was observed. Cosmetic results appear to be excellent. All patients were treated with intraperitoneal hyperthermia and chemotherapy. The survival rate was 100%. As a novel scarless endoscopic invasive abdominal surgery, TUES has high clinical value with the advantages such as small trauma, no scars, small risk and low cost in the diagnosis of unexplained ascites.

[Efficacy and safety of peroral endoscopic myotomy in the treatment of achalasia cardia].

OBJECTIVE: To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) for achalasia cardia (AC).
 METHODS: A total of 62 patients with AC were enrolled and treated with POEM in the Third Xiangya Hospital, Central South University from April 2012 to October 2014. The symptoms and complications were retrospectively analyzed.
 RESULTS: The ages of patients, including 32 males and 30 females, were 14-68 (43.2±5.6) years old. Eckardt scores were 4-6 or ≥7 for 25 patients or 37 patients (including 20 patients were at a score of 12). Thirteen patients suffered balloon expansion for 2-3 times. Sixty-one patients had completed POEM treatment, 1 patient were given Heller surgery instead of POEM because of extensive submucosal adhesion during POEM. The operative time for POEM was (60.8±15.1) min. Fourteen patients had mild subcutaneous emphysema. Among them, 5 suffered pneumoperitoneum and felt better after abdominal puncture exhaust; 2 patients suffered bronchospasm hypoxemia and were relieved after treatment by positive pressure oxygen for 1 h. The hospital stay was (4.3±1.2) d. The postoperative follow-up period was (11.4±5.4) months. Swallowing obstruction, vomiting and chest pain in patients was relieved at different degrees. The treatment effective rate was 100%. 
 CONCLUSION: POEM is a safe, effective and minimally invasive approach for AC.

[Application of endoscopic full-thickness resection in the treatment of gastric tumors originated fromthe muscularis propria].

OBJECTIVE: To evaluate the curative effect and safety of endoscopic full-thickness resection (EFR) in the treatment of gastric tumor originated from the muscularis propria.
 METHODS: Clinical data were collected from 34 patients, who underwent EFR of gastric tumor originated from muscularis propria, to observe the resection rate and complications from November 2012 to August 2014.
 RESULTS: Of the 34 patients, 15 were male, 19 were female, with the age of 38.3-70.6 (52.3±4.3) years old. The lesions of 25 patients located in the fundus of stomach and the rest was in the gastric body. EFR was successfully performed in the 34 patients with no need for surgery. The complete resection rate was 100%. Lesion diameter ranged from 1.0 to 5.0 (2.8±1.2) centimeters. The operation time was 50-100 (76.5±18.2) min. Patients with pneumoperitoneum were relieved after abdominal puncture exhaust, without post-operation bleeding and perforation. The hospitalization duration was 3-5 (3.6±0.8) days. Except 1 case, the remaining 33 cases were spindle cell tumors, consistent with the results of immunohistochemistry. The risk for two lesions with 4.5 cm and 5.0 cm was moderate. The risk of invasion was low or very low in the remaining 31 cases. Among them, 2 stromal tumors near the cardia showed a differentiation tendency toward smooth muscle. No lesion residual or recurrence happened during the follow-up period (range 5-23 months) in 34 cases. 
 CONCLUSION: EFR is a safe and effective method for gastric tumor originated from muscularis propria.

[A case of complex Crohn's disease with severe complication].

Crohn's disease (CD) is a nonspecific chronic intestinal inflammatory disease with unknown etiology. The course of CD is persistent and recurrent. In the progress, CD can come with many complications such as obstruction, fistula formation, perforation, and hemorrhage. The early diagnosis, treatment, and the time of the surgery for CD pose a big controversy and challenge. There was a female patient diagnosed as Crohn's disease with severe complication in department of Gastroenterology of the Third Xiangya Hospital, Central South University.  We reported the diagnosis and treatment on this patient. The choice for the medicine and surgury was discussed.

Inflammation-induced S100A8 activates Id3 and promotes colorectal tumorigenesis.

The aberrant expression of S100A8 and S100A9 is linked to nonresolving inflammation and ultimately to carcinogenesis, whereas the underlying mechanism that allows inflammation to progress to specific cancer types remains unknown. Here, we report that S100A8 was induced by inflammation and then promoted colorectal tumorigenesis downstream by activating Id3 (inhibitor of differentiation 3). Using gene expression profiling and immunohistochemistry, we found that both S100A8 and S100A9 were upregulated in the chemically-induced colitis-associated cancer mouse model and in human colorectal cancer specimens. Furthermore, we showed that S100A8 and S100A9 acted as chemoattractant proteins by recruiting macrophages, promoting the proliferation and invasion of colon cancer cell, as well as spurring the cycle that culminates in the acceleration of cancer metastasis in a nude mouse model. S100A8 regulated colon cancer cell cycle and proliferation by inducing Id3 expression while inhibiting p21. Id3 expression was regulated by Smad5, which was directly phosphorylated by Akt1. Our study revealed a novel mechanism in which inflammation-induced S100A8 promoted colorectal tumorigenesis by acting upstream to activate the Akt1-Smad5-Id3 axis.

LY294002 and Rapamycin promote coxsackievirus-induced cytopathic effect and apoptosis via inhibition of PI3K/AKT/mTOR signaling pathway.

Coxsackievirus B3 (CVB3) is a common human pathogen for acute myocarditis, pancreatitis, non-septic meningitis, and encephalitis; it induces a direct cytopathic effect (CPE) and apoptosis on infected cells. The Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT/PKB)/mammalian target of Rapamycin (mTOR) signaling pathway regulates several cellular processes and it is one of the most important pathways in human networks. However, the effect and mechanism of PI3K/AKT/mTOR signaling pathway in CVB3 infected cells are poorly understood. In this study, we demonstrate that inhibition of PI3K/AKT/mTOR signaling pathway increased CVB3-induced CPE and apoptosis in HeLa cells. The activity of downstream targets of PI3K and mTOR is attenuated after CVB3 infection and inhibitors of PI3K and mTOR made their activity to decrease more significantly. We further show that LY294002 and Rapamycin, the inhibitor of PI3K and mTOR respectively, promote CVB3-induced CPE and apoptosis. Taken together, these data illustrate a new and imperative role for PI3K/AKT/mTOR signaling in CVB3 infection in HeLa cells and suggest an useful approach for the therapy of CVB3 infection.

[Effect of Feridex-GFP double-labeled BMSC transplant on the damaged liver under the condition of constant magnetic field].

OBJECTIVE: To evaluate the effect of the bone marrow mesenchymal stem cells (BMSCs) transplant through peripheral vein, portal vein and hepatic artery into liver under the condition of constant magnetic field and to analyze the therapeutic effect on liver function recovery. METHODS: BMSCs were isolated, purified and induced to differentiate into liver-like cells, which were double labeled by Feridex-GFP. The double-labeled BMSCs were transplanted into liver through different ways including peripheral vein, portal vein and hepatic artery with or without constant magnetic field in vitro. The rats were sacrificed at the 1st, 2nd, 3rd and 4th week after the transplant. ALB, ALT, AST were tested. The liver tissue biopsy was collected. GFP-positive cells in liver were observed by fluorescence microscopy. RESULTS: Double-labeled BMSCs could be transplanted into liver through all ways. GFP expression was found in liver in all groups at the 4th week and the liver functions were improved. Based on the long term efficacy, the liver functions recovered more rapidly in the portal vein + constant magnetic field group and the hepatic artery + constant magnetic field group. CONCLUSION: BMSCs transplantation can reduce acute liver damage. The first choice for BMSCs transplantation was via portal vein or hepatic artery under the condition of constant magnetic field. The second choice was via peripheral vein alone or under the condition of constant magnetic field.

MiR-126 suppresses colon cancer cell proliferation and invasion via inhibiting RhoA/ROCK signaling pathway.

Recent data strongly suggests the profound role of miRNAs in cancer progression. Here, we showed miR-126 expression was much lower in HCT116, SW620 and HT-29 colon cancer cells with highly metastatic potential and miR-126 downregulation was more frequent in colorectal cancers with metastasis. Restored miR-126 expression inhibited HT-29 cell growth, cell-cycle progression and invasion. Mechanically, microarray results combined with bioinformatic and experimental analysis demonstrated miR-126 exerted cancer suppressor role via inhibiting RhoA/ROCK signaling pathway. These results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies.

Endoscopic ultrasound diagnosis system based on deep learning in images capture and segmentation training of solid pancreatic masses.

BACKGROUND: Early detection of solid pancreatic masses through contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) is important. But CH-EUS is difficult to learn. PURPOSE: To design a deep learning-based CH-EUS diagnosis system (CH-EUS MASTER) for real-time capture and segmentation of solid pancreatic masses and to verify its value in the training of pancreatic mass identification under endoscopic ultrasound (EUS). METHODS: We designed a real-time capture and segmentation model for solid pancreatic masses and then collected 4530 EUS images of pancreatic masses retrospectively, used for training and testing of this model at a ratio of 8:2. The model is loaded into the EUS host computer to establish the CH-EUS MASTER system. A crossover trial was then conducted to evaluate the model's value in EUS trainee training by successfully conducting two groups of EUS trainees in model learning and trainer-guided training. The intersection over union (IoU) and the time to find the lesion were used to evaluate the model performance metrics, and the Mann-Whitney test was used to compare the IoU and the time to find the lesion in different groups of subjects. Paired t-test was used to compare the effects before and after training. When α ≤ 0.05, it is considered to have a significant statistical difference. RESULTS: The model test showed that the model successfully captured and segmented the pancreatic solid mass region in 906 EUS images. The real-time capture and segmentation model had a Dice coefficient of 0.763, a recall rate of 0.941, a precision rate of 0.642, and an accuracy of 0.842 (when the threshold is set to 0.5), and the median IoU of all cases was 0.731. For the AI training effect, the average IoU of eight trainees improved from 0.80 to 0.87 (95% CI, 0.032-0.096; p = 0.002). The average time for identifying lesions in the pancreatic body and tail improved from 22.75 to 17.98 s (95% CI, 3.664-5.886; p < 0.01). The average time for identifying lesions in the pancreatic head and uncinate process improved from 34.21 to 25.92 s (95% CI, 7.661-8.913; p < 0.01). CONCLUSION: CH-EUS MASTER can provide an effect equivalent to trainer guidance in training pancreatic solid mass identification and segmentation under EUS.

The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori.

Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism. Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism. Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome. Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05097846.

Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) MASTER: A novel deep learning-based system in pancreatic mass diagnosis.

BACKGROUND AND AIMS: Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning-based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS-guided fine-needle aspiration (EUS-FNA) in real time. METHODS: This is a prospective study. The CH-EUS MASTER system is composed of Model 1 (real-time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH-EUS examinations followed by EUS-FNA were recruited. All patients underwent CH-EUS and were diagnosed both by endoscopists and CH-EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS-FNA with or without CH-EUS MASTER guidance. RESULTS: Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH-EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH-EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH-EUS MASTER guided EUS-FNA, and were not significantly different compared to the control group. CH-EUS MASTER-guided EUS-FNA significantly improved the first-pass diagnostic yield. CONCLUSION: CH-EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. TRIAL REGISTRATION NUMBER: NCT04607720.

Dynamic activation of the key pathways: linking colitis to colorectal cancer in a mouse model.

An association between carcinogenesis and inflammation has long been appreciated. Chemically induced colitis-associated cancer (CAC) is a classical mouse model for investigating 'inflammation-cancer link' in the intestine. Diverse mechanisms behind this non-resolving inflammation model have been reported before, most of them were emphasized on key cancer genes, cytokines, and signal transduction abnormality based on prior knowledge. In this study, we dynamically and globally dissect the alteration of key pathways in the development from colitis to colorectal cancer. Striking evidence from gene expression profiling, serum cytokines detection, and immunohistochemistry analysis all reveals that different key pathways [NF-κB, STAT3, p38 mitogen-activated protein kinase (MAPK), and Wnt/ß-catenin signaling] and their target genes are hyperactive in different phases of the inflammation-cancer link. Nuclear factor-κB (NF-κB) and STAT3 signaling are hyperactive in the whole process, while p38 MAPK and Wnt/ß-catenin signaling are only hyperactive in the beginning and ending, respectively. Through this unbiased system biological approach, we provide strong evidence that different key pathways are specifically involved in different phases, which bridge the gap between inflammation and cancer.

HMOX1 promotes lung adenocarcinoma metastasis by affecting macrophages and mitochondrion complexes.

Background: Metastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis. Methods: Pan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network. Results: HMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin. Conclusions: Our analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.

Circular RNA KIF4A Promotes Liver Metastasis of Breast Cancer by Reprogramming Glucose Metabolism.

Background: Circular RNAs (circRNAs) regulate complex functional processes and play crucial roles in cancer development and progression. It was reported that circKIF4 regulates the progression of triple-negative breast cancer (TNBC). This study evaluates the role of circKIF4 in breast cancer distant metastasis and metabolic reprogramming. Methods: RT-qPCR was performed to verify the expression of circKIF4A in breast cancer, liver metastatic tissues, and cell lines. The function of circKIF4A in metastasis was evaluated both in vitro and in vivo through a series of experiments, including cell migration and glucose intake experiments. Additionally, we conducted molecular experiments to clarify the regulatory role of circKIF4A. We then conducted a Luciferase reporter assay and an RNA immunoprecipitation assay to identify the molecular interactions between circKIF4A and miRNA. Results: circKIF4A was overexpressed in breast cancer cell lines and tissues, inhibiting its expression and suppressing breast cancer growth and metastasis. Interestingly, we observed that circKIF4A reprogrammed the glucose metabolism of breast cancer, and silencing circKIF4A greatly affected glucose uptake and lactate production in breast cancer cells. miR-335 can be sponged by circKIF4A, which affected the expression of ALDOA/OCT4 protein and regulated HK2/PKM2 expression. Conclusions: This study demonstrated that the circKIF4A-miR-335-OCT4/ALDOA-HK2/PKM2 axis is critical to breast cancer metabolic reprogramming, indicating that this axis could be a novel therapeutic target for the treatment of liver metastasis of breast cancer.