ABSTRACT
Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.
ABSTRACT
BACKGROUND: Endoscopic ultrasonography (EUS) is recommended as the best tool for evaluating gastric subepithelial lesions (SELs); nonetheless, it has difficulty distinguishing gastrointestinal stromal tumors (GISTs) from leiomyomas and schwannomas. GISTs have malignant potential, whereas leiomyomas and schwannomas are considered benign. PURPOSE: This study aimed to establish a combined radiomic model based on EUS images for distinguishing GISTs from leiomyomas and schwannomas in the stomach. METHODS: EUS images of pathologically confirmed GISTs, leiomyomas, and schwannomas were collected from five centers. Gastric SELs were divided into training and testing datasets based on random split-sample method (7:3). Radiomic features were extracted from the tumor and muscularis propria regions. Principal component analysis, least absolute shrinkage, and selection operator were used for feature selection. Support vector machine was used to construct radiomic models. Two radiomic models were built: the conventional radiomic model included tumor features alone, whereas the combined radiomic model incorporated features from the tumor and muscularis propria regions. RESULTS: A total of 3933 EUS images from 485 cases were included. For the differential diagnosis of GISTs from leiomyomas and schwannomas, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were 74.5%, 72.2%, 78.7%, and 0.754, respectively, for the EUS experts; 76.8%, 74.4%, 81.0%, and 0.830, respectively, for the conventional radiomic model; and 90.9%, 91.0%, 90.6%, and 0.953, respectively, for the combined radiomic model. For gastric SELs <20 mm, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the combined radiomic model were 91.4%, 91.6%, 91.1%, and 0.960, respectively. CONCLUSIONS: We developed and validated a combined radiomic model to distinguish gastric GISTs from leiomyomas and schwannomas. The combined radiomic model showed better diagnostic performance than the conventional radiomic model and could assist EUS experts in non-invasively diagnosing gastric SELs, particularly gastric SELs <20 mm.
Subject(s)
Gastrointestinal Stromal Tumors , Leiomyoma , Neurilemmoma , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Endosonography , Stomach Neoplasms/diagnostic imaging , Leiomyoma/diagnostic imaging , Leiomyoma/pathology , Neurilemmoma/diagnostic imaging , Stomach/pathologyABSTRACT
BACKGROUND: There are many studies on submucosal injection materials, but their clinical use is restricted for various reasons. The objective of this study was to compare the feasibility and safety of injected EndoClot®SIS polysaccharide as a submucosal injection material (SFC) in ESD in the pig stomach to that of injected sigMAVisc™ or Eleview™. METHODS: Four pig stomachs were used for the ex vivo study. Eighteen pigs were used for the in vivo study. In the ex vivo study, four injections were made in the gastric submucosa to induce submucosal uplift and extend its duration. Tissue change was observed. The in vivo study was performed in 2 steps. First, 3 injections were made in the esophageal mucosa to induce submucosal uplift and extend its duration. Histological change was observed. Second, ESD was performed in the stomach by injecting EndoClot®SIS polysaccharide, sigMAVisc™, or Eleview™ (each, n = 6) as an SFC. The effects of these agents on wound healing were examined. We evaluated the efficacy and safety of endoscopic surgery after EndoClot®SIS polysaccharide injection. RESULTS: EndoClot®SIS polysaccharide produced a longer-lasting elevation with clearer margins than was achieved by sigMAVisc™, Eleview™, or 0.9% NaCl and thereby enabled precise ESD without complications, such as bleeding and perforation. No obvious histopathological damage was observed at the injection site on endoscopy and histology. CONCLUSION: Submucosally injected EndoClot®SIS polysaccharide increased the effective separation of the mucosa and submucosa and reduced surgical complications. Hence, EndoClot®SIS polysaccharide injection is a safe and effective submucosal injection material.
Subject(s)
Endoscopic Mucosal Resection , Gastric Mucosa , Intraoperative Complications/prevention & control , Polysaccharides/pharmacology , Starch/analogs & derivatives , Animals , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Excipients/pharmacology , Gastric Mucosa/pathology , Gastric Mucosa/surgery , Injections/methods , Male , Models, Animal , Preoperative Care/methods , Starch/pharmacology , Swine , Swine, MiniatureABSTRACT
BACKGROUND AND AIMS: Various methods have been reported as aids to cecal intubation. This study aimed to prospectively investigate whether an abdominal obstetric binder (AOB) used during pregnancy and attached to the patients' abdomen during colonoscopy could facilitate effective colonoscopic insertion. METHODS: This was a prospective study of 451 consecutive outpatient colonoscopies performed by a single experienced endoscopist. The recruited patients were randomly separated into two groups that received colonoscopy either with (Group A) or without an AOB attached (Group B). The cecal intubation time, cecal intubation length of the colonoscope, use of manual pressure, position change of each patient, and the number of patients with abdominal distension were collected for comparison. RESULTS: A total of 451 patients (224 in Group A and 227 in Group B) were ultimately included in this study. In Group A, cecal intubation time and cecal intubation length of colonoscope (CIL) were significantly reduced (P < 0.001). The patients had significantly fewer position changes and manual pressure in Group A (P < 0.001). Significantly less abdominal distension was reported by patients in Group A (P < 0.001). CONCLUSIONS: During colonoscopy, the application of an AOB provided a significantly faster and more effective colonoscope insertion.
Subject(s)
Bandages , Colonoscopy/methods , Intubation, Gastrointestinal/methods , Abdomen , Adolescent , Adult , Aged , Aged, 80 and over , Cecum , Humans , Male , Middle Aged , Operative Time , Prospective Studies , Young AdultABSTRACT
BACKGROUND/OBJECTIVES: Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS: AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS: AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS: Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.
Subject(s)
Autophagy , Pancreatitis/physiopathology , TOR Serine-Threonine Kinases/metabolism , Acute Disease , Animals , Biomarkers/metabolism , Blotting, Western , Disease Progression , In Situ Nick-End Labeling , Lysosomes/physiology , Male , Pancreatitis/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND/AIMS: To investigate the effects of edaravone, a potent free radical scavenger, on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and pancreatic fibrosis. METHODS: Male Sprague-Dawley rats were randomly divided into four groups (n = 16 each): control, DBTC, DBTC + edaravone, and control + edaravone. Edaravone or normal saline at a daily dose of 6 mg/kg body weight was given intraperitoneally from day 5 to day 28 after DBTC administration. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression of cytokines in pancreas TGF-ß, IL-6 and TNF
Subject(s)
Antipyrine/analogs & derivatives , Organotin Compounds/toxicity , Pancreatitis, Chronic/chemically induced , Actins/genetics , Actins/metabolism , Animals , Antipyrine/pharmacology , Chronic Disease , Cytokines/genetics , Cytokines/metabolism , Edaravone , Gene Expression Regulation/drug effects , Hydroxyproline , Male , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolismABSTRACT
BACKGROUND: Distinguishing malignant from benign pancreatic tumors is challenging with current imaging techniques. Endoscopic ultrasound (EUS) elastography has further improved the efficacy of EUS for characterizing pancreatic lesions. AIMS: To assess, by combining data from existing trials, the accuracy of EUS elastography in diagnosing malignant tumors for patients with pancreatic masses. METHODS: All relevant studies published were identified by systematic searching of databases. A meta-analysis was performed using a random-effects model to combine study results. RESULTS: Seven studies involving 752 patients were included. The sensitivity of EUS elastography for differential diagnosis of solid pancreatic masses was 97 % (95 % CI, 0.95-0.98), and the specificity was 76 % (95 % CI, 0.69-0.82). The area under the curve under summary receiver operating characteristic (SROC) was 0.9529. The combined positive likelihood ratio was 3.71 (95 % CI, 2.72-5.07), and the negative likelihood ratio was 0.05 (95 % CI, 0.02-0.13). CONCLUSION: Our meta-analysis shows that EUS elastography is a useful tool for differential diagnosis of solid pancreatic neoplasms with very high sensitivity and relatively low specificity. The results indicate that EUS elastography not only provides information complementary to that from EUS but also potentially increases the yield of fine needle aspiration and reduces the number of unnecessary biopsies.
Subject(s)
Pancreatic Neoplasms/diagnostic imaging , Diagnosis, Differential , Elasticity Imaging Techniques , Endosonography , Humans , Publication BiasABSTRACT
BACKGROUND: Distinguishing pancreatic adenocarcinomas from other pancreatic masses remains challenging with current imaging techniques. Contrast-enhanced EUS further improved the efficacy of EUS to characterize pancreatic lesions. OBJECTIVE: To assess the accuracy of contrast-enhanced EUS for diagnosing adenocarcinoma in patients with pancreatic masses by pooling data of existing trials. DESIGN: We systematically searched the Medline, PubMed, Web of Science, Embase, and Cochrane Central Trials databases for relevant studies published. Meta-analysis was performed. Pooling was conducted in a fixed-effect model or a random-effects model. PATIENTS: Twelve studies involving 1139 patients were included. INTERVENTION: Contrast-enhanced EUS. MAIN OUTCOME MEASUREMENTS: Meta-analysis and meta-regression analysis. RESULTS: The pooled sensitivity of contrast-enhanced EUS for the differential diagnosis of pancreatic adenocarcinomas was 94% (95% CI, 0.91-0.95), and the specificity was 89% (95% CI, 0.85-0.92). The area under the curve under summary receiver operating characteristic was 0.9732. The pooled positive likelihood ratio was 8.09 (95% CI, 4.47-14.64), and the negative likelihood ratio was 0.08 (95% CI, 0.06-0.10). The subgroup analysis by exclusion of the outliers provided a sensitivity of 93% (95% CI, 0.91-0.95) and a specificity of 93% (95% CI, 0.89-0.95) for the differential diagnosis of pancreatic adenocarcinomas. The area under the curve under summary receiver operating characteristic was 0.9745. LIMITATIONS: A small number of studies met the inclusion criteria. CONCLUSION: Contrast-enhanced EUS is a promising, reliable modality for the differential diagnosis of pancreatic adenocarcinoma in patients with pancreatic mass lesions. The finding of a hypoenhanced lesion was a sensitive and accurate predictor of pancreatic adenocarcinomas. It seems to be a useful tool in clinical practice.
Subject(s)
Adenocarcinoma/diagnostic imaging , Contrast Media , Endosonography/methods , Pancreatic Neoplasms/diagnostic imaging , Diagnosis, Differential , Humans , Models, Statistical , Regression Analysis , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP). METHODS: A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 µg/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-10, intercellular adhesion molecule (ICAM-1), E-selectin and nuclear factor (NF)-κB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-κB p65 protein was also measured by immunohistochemistry. RESULTS: Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 ± 1.3 vs 11.3 ± 1.5, 24 h: 7.8 ± 1.1 vs 11.7 ± 0.8) and the amount of ascites was lower(12 h: (6.88 ± 1.23) ml vs (12.32 ± 1.94) ml, 24 h: (6.53 ± 0.91) ml vs (14.15 ± 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4)-ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-α mRNA, IL-1ß mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-κB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-κB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% ± 3.0% vs 45.3% ± 3.4%, 24 h: 31.6% ± 3.0% vs 48.1% ± 4.6%, both P < 0.01). CONCLUSION: LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-κB activation.
Subject(s)
Lipoxins/pharmacology , Lipoxins/therapeutic use , Pancreatitis/drug therapy , Pancreatitis/metabolism , Acute Disease , Animals , Intercellular Adhesion Molecule-1/metabolism , Male , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: Linked color imaging (LCI) is a recently developed technique that emphasizes differences in mucosal color. In this study we aimed to develop a LCI classification based on the Narrow-band Imaging International Colorectal Endoscopic Classification for predicting colorectal polyp histology and evaluate the validity and performance of the endoscopists in differentiating hyperplastic polyps from adenomas using the LCI classification. METHODS: A workshop involving six international experts from China and Japan with substantial experience with LCI developed the classification. Three experienced and seven less-experienced endoscopists used the LCI images to predict the histology of polyps independently, recording their degrees of confidence in these predictions before and after completing the training test for the LCI classification. RESULTS: Of the 50 polyps included, 30 (60.0%) were adenomas. Overall diagnostic accuracy before training was 75.4% (95% confidence interval [CI] 71.4%-79.1%), which increased to 85.2% (95% CI 81.8%-88.2%) after training. After training, the experienced and less-experienced endoscopists achieved an overall accuracy of 87.3% and 84.3% for the prediction of polyp histology. Polyp prediction using the color criterion alone had the highest specificity and positive predictive value, whereas the vessel criterion achieved the highest accuracy and negative predictive value among all three individual LCI criteria. After training, both the experienced and less-experienced endoscopists had high degrees of interobserver agreement. CONCLUSIONS: We developed and validated the first LCI classification for endoscopic differentiation of adenomas and hyperplastic polyps. The LCI classification significantly improved the diagnostic accuracy of colorectal polyps.
Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Adenoma/diagnostic imaging , Adenoma/pathology , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colonoscopy/methods , Color , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Humans , Narrow Band Imaging/methods , Predictive Value of TestsABSTRACT
Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.
ABSTRACT
Procalcitonin (PCT) is widely used to diagnose a bacterial infection. An increased serum PCT can also be observed in tumors. We presented an unusual case of a metastatic PNET producing and secreting PCT. Immunohistochemistry was used to demonstrate that PCT can be secreted by PanNET.
ABSTRACT
BACKGROUND: Adenomyomatous hyperplasia of the distal common bile duct (CBD) is very rare, with only scarce case reports in the literature. Diagnosis is usually based on imaging findings, and endoscopic biopsy is very difficult before operation. It is believed that adenomyomatous hyperplasia has little or no risk of malignant transformation. CASE SUMMARY: A 68-year-old woman with abdominal pain in the right upper quadrant was referred to our hospital. Abdominal ultrasonography in the emergency ward revealed acute cholecystitis and dilated CBD. Laboratory findings showed elevated levels of transaminases, phosphatase, and γ-glutamyltranspeptidase. Pharmaceutical treatment for 3 d did not relieve the symptoms. Magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) showed proximal bile duct dilatation but could not identify the cause. Endoscopic ultrasonography (EUS) demonstrated a mixed echogenic mass in the distal CBD. During surgery, a firm mass was found in the distal CBD and the Whipple procedure was performed with the initial concern of malignancy. Histology showed diffuse adenomyomatous hyperplasia. CONCLUSION: EUS may be a useful choice to diagnose adenomyoma of the distal CBD before operation, especially in patients with ambiguous MRCP/CT findings.
ABSTRACT
BACKGROUND/AIM: To compare the efficacy and tolerance of different proton pump inhibitors (PPIs) in different doses for patients with duodenal ulcers. MATERIALS AND METHODS: An electronic database was searched to collect all randomized clinical trials (RCTs), and a pairwise and network meta-analysis were performed. RESULTS: A total of 24 RCTs involving 6188 patients were included. The network meta-analysis showed that there were no significant differences for the 4-week healing rate of duodenal ulcer treated with different PPI regimens except pantoprazle 40 mg/d versus lansoprazole 15 mg/d [Relative risk (RR) = 3.57; 95% confidence interval (CI) = 1.36-10.31)] and lansoprazole 30 mg/d versus lansoprazole 15 mg/d (RR = 2.45; 95% CI = 1.01-6.14). In comparison with H2receptor antagonists (H2RA), pantoprazole 40 mg/d and lansoprazole 30 mg/d significantly increase the healing rate (RR = 2.96; 95% CI = 1.78-5.14 and RR = 2.04; 95% CI = 1.13-3.53, respectively). There was no significant difference for the rate of adverse events between different regimens, including H2RA for a duration of 4-week of follow up. CONCLUSION: There was no significant difference for the efficacy and tolerance between the ordinary doses of different PPIs with the exception of lansoprazle 15 mg/d.
Subject(s)
Duodenal Ulcer/drug therapy , Proton Pump Inhibitors/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use , Drug Administration Schedule , Humans , Lansoprazole/administration & dosage , Lansoprazole/therapeutic use , Network Meta-Analysis , Pantoprazole , Proton Pump Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
AIMS: Thioredoxin-interacting protein (TXNIP) is associated with activation of oxidative stress through inhibition of thioredoxin (Trx). However, some evidences point out that TXNIP acts as a scaffolding protein in signaling complex independent of cellular redox regulation. The autophagy-lysosomal pathway plays important roles in the clearance of misfolded proteins and dysfunctional organelles. Lysosomal dysfunction has been involved in several neurodegenerative disorders including Parkinson's disease (PD). Although researchers have reported that TXNIP inhibited autophagic flux, the specific mechanism is rarely studied. METHODS: In this study, we investigated the effects of TXNIP on autophagic flux and α-synuclein accumulation by Western blot in HEK293 cells transfected with TXNIP plasmid. Further, we explored the influence of TXNIP on DA neuron survival in substantia nigra by IHC. RESULTS: We found that TXNIP induced LC3-II expression, but failed to degrade p62, a substrate of autophagy. Also, TXNIP aggravated α-synuclein accumulation. We also found that TXNIP inhibited the expression of ATP13A2, a lysosomal membrane protein. Moreover, we found that overexpression of ATP13A2 attenuated the impairment of autophagic flux and α-synuclein accumulation induced by TXNIP. Furthermore, overexpression of TXNIP in substantia nigra resulted in loss of DA neuron. CONCLUSION: Our data suggested that TXNIP blocked autophagic flux and induced α-synuclein accumulation through inhibition of ATP13A2, indicating TXNIP was a disease-causing protein in PD.
Subject(s)
Autophagy/genetics , Carrier Proteins/metabolism , Mesencephalon/metabolism , alpha-Synuclein/metabolism , AMP-Activated Protein Kinase Kinases , Adenosine Triphosphatases/metabolism , Animals , Carrier Proteins/genetics , Cell Death/genetics , Cell Line, Transformed , Dopaminergic Neurons/metabolism , Gene Expression Regulation/genetics , Humans , Lentivirus/genetics , Membrane Proteins/metabolism , Mesencephalon/cytology , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/metabolism , Mutation/genetics , Peptides/metabolism , Protein Kinases/metabolism , Proton-Translocating ATPases , TransfectionABSTRACT
AIM: Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA) on sodium channel activities and colonic hypersensitivity of rats with diabetes. METHODS: Streptozotocin was used to induce diabetes in adult female rats. Colonic sensitivity was measured by behavioral responses to colorectal distention in rats. The excitability and sodium channel currents of colon projection DRG neurons labeled with DiI were measured by whole-cell patch-clamp recordings. The expressions of NaV1.7 and NaV1.8 of colon DRGs were measured by western blot analysis. RESULTS: ALA treatment significantly increased distention threshold in responding to colorectal distension in diabetic rats compared with normal saline treatment. ALA treatment also hyper-polarized the resting membrane potentials, depolarized action potential threshold, increased rheobase, and decreased frequency of action potentials evoked by ramp current stimulation. Furthermore, ALA treatment also reduced neuronal sodium current densities of DRG neurons innervating the colon from rats with diabetes. In addition, ALA treatment significantly downregulated NaV1.7 and NaV1.8 expression in colon DRGs from rats with diabetes. CONCLUSION: Our results suggest that ALA plays an analgesic role, which was likely mediated by downregulation of NaV1.7 and NaV1.8 expressions and functions, thus providing experimental evidence for using ALA to treat colonic hypersensitivity in patients with diabetic visceral pain.
ABSTRACT
OBJECTIVE: To provide a retrospective assessment of clinical characteristics of the patients with gastric glomus tumors and the imaging features of the tumors on multidetector row computed tomography (MDCT). METHODS: Consecutive patients with gastric glomus tumor which was confirmed by postoperative pathology from January 2004 to January 2012 in a tertiary hospital were included in the study. The MDCT images and medical records of the patients including the imaging features of the tumor on MDCT such as its location, number, shape, growth pattern, size, density and enhancement pattern were retrospectively reviewed. RESULTS: Altogether ten patients were included in the study, including seven women and three men, with a mean age of 46.6 years (range 25-67 years). Most patients had nonspecific clinical symptoms. All lesions were located at the gastric antrum, with a mean diameter of 2.7 cm. The gastric glomus tumor showed strong enhancement at the arterial phase, a progressive filled-in enhanced pattern and prolonged enhancement during multiphasic scans. CONCLUSIONS: Gastric glomus tumor is clinically an extremely rare disease. The combination of tumor location, size and the characteristic enhancement pattern of the subepithelial lesion may suggest a diagnosis of gastric glomus tumor.
Subject(s)
Glomus Tumor/diagnostic imaging , Stomach Neoplasms/diagnostic imaging , Adult , Aged , Female , Gastrectomy/methods , Gastroscopy/methods , Glomus Tumor/surgery , Humans , Male , Middle Aged , Pyloric Antrum , Retrospective Studies , Stomach Neoplasms/surgery , Tomography, X-Ray Computed/methodsABSTRACT
eEF1A2 is a protein translation factor involved in protein synthesis that is overexpressed in various cancers, with important functions in tumor genesis and progression. We have previously showed that the ectopic expression of eEF1A2 is correlated with lymph node metastasis and perineural invasion in pancreatic cancer. In this study, we investigated the functional role of eEF1A2 in the regulation of cell migration, invasion, and metastasis in pancreatic cancer. Furthermore, we investigated the potential molecular mechanisms involved. By evaluating the invasive ability of a panel of pancreatic cancer cell lines with different metastatic potentials, eEF1A2 expression in cells was positively associated with their invasive ability. The knockdown of eEF1A2 by siRNA decreased the migration and invasion of PANC-1 cells. By contrast, the ectopic expression of exogenous eEF1A2 significantly promoted the migration and invasion of SW1990 cells. Stable eEF1A2 overexpression in a nude mouse model of peritoneal metastasis likewise dramatically enhanced the intraperitoneal metastatic ability of SW1990 cells. In addition, eEF1A2 overexpression could upregulate MMP-9 expression and activity. A significant positive correlation between the overexpression of both eEF1A2 and MMP-9 was observed in pancreatic cancer tissues. The inhibition of MMP-9 activity reduced the promoting effect of eEF1A2 on cell migration and invasion. Furthermore, eEF1A2-mediated cell migration and invasion, as well as MMP-9 expression and upregulation, were largely dependent on the eEF1A2-induced Akt activation. The findings suggested the potentially important role of eEF1A2 in pancreatic cancer migration, invasion, and metastasis. Thus, the results provide evidence of eEF1A2 as a potential therapeutic target in the treatment of aggressive pancreatic cancer.