Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma.

NTRK fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in NTRK-positive solid tumors. Although some NTRK fusion partners have been identified in thyroid cancer, the spectrum of NTRK fusion is not fully characterized. In this study, a dual NTRK3 fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between NTRK3 exon 13 and AJUBA exon 2, co-existing with a known in-frame fusion between ETV6 exon 4 and NTRK3 exon 14. The dual NTRK3 fusion was validated by Sanger sequencing and fluorescence in situ hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer. These findings extend the spectrum of translocation partners in NTRK3 fusion, and the effect of dual NTRK3 fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.

Neutrophil-to-lymphocyte ratio is associated with malnutrition risk estimated by the Royal Free Hospital-Nutritional Prioritizing Tool in hospitalized cirrhosis.

BACKGROUND: Liver cirrhosis is characterized by immune dysfunction, contributing to malnutrition. We previously revealed neutrophil-to-lymphocyte ratio (NLR) as an indicator of disordered immune system. Herein we aimed to (1) determine the optimal NLR cutoff that best predicts malnutrition risk and (2) clarify the association between NLR and nutrition status. METHODS: A total of 135 hospitalized patients with cirrhosis were included. Immune dysfunction was evaluated by levels of serum C-reactive protein (CRP), NLR, and other parameters. Malnutrition was screened by a risk score referring to the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Receiver operating characteristic (ROC) curve was implemented to determine the best NLR cutoff that predicts malnutrition risk. Correlation between NLR and indicators of hepatic and physical function (handgrip strength) were also examined. Multivariable logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS: ROC curve revealed that the optimum cutoff to predict malnutrition risk was NLR > 4.2, with a sensitivity of 47.2%, specificity of 81.0%, negative predictive value of 58.0%, and positive predictive value of 74.5%, respectively. Patients with NLR > 4.2 exhibited a higher RFH-NPT score, serum platelet-to-lymphocyte ratio, and CRP. A positive correlation was found between NLR values and Child-Turcotte-Pugh (r = 0.22; P = .010), model for end-stage liver disease (r = 0.36; P < .001), and RFH-NPT scores (r = 0.31; P < .001). NLR was a risk factor for malnutrition independently of alcoholic liver disease and presence of ascites. CONCLUSIONS: Immune dysfunction measured by NLR was associated with malnutrition risk estimated by RFH-NPT in cirrhosis.

Relationship between sarcopenia/myosteatosis and frailty in hospitalized patients with cirrhosis: a sex-stratified analysis.

BACKGROUND: Previous studies have shown that sarcopenia appears to be a significant contributor to physical frailty among outpatients with cirrhosis. However, the evidence is scant regarding the relationship between sarcopenia and multi-dimensional frailty among inpatients. We aimed to investigate the potential contribution of sarcopenia to frailty in hospitalized patients with cirrhosis in a sex-dependent manner. METHODS: This cohort enrolled consecutive cirrhotics. Muscle quantity and quality were assessed using the computed tomography-based skeletal muscle index (SMI) and intramuscular adipose tissue content, respectively. Frailty phenotype was clarified by a self-reported Frailty Index. Multiple linear regression determined the association between sarcopenia and frailty phenotype. RESULTS: A total of 202 cirrhotic patients with 48.5% male were included. The median Frailty Index was 0.13, rendering 17.3% subjects as frail. Among the 16 frail men, 68.8% had sarcopenia and 62.5% exhibited myosteatosis. In contrast, among the 19 frail women, 26.3% had sarcopenia and 15.8% exhibited myosteatosis. Frail patients had a significantly lower median SMI (42.80 cm2/m2) compared with those with pre-frailty (48.23 cm2/m2) and with robust status (50.82 cm2/m2) in the male but not the female group. In male patients, multivariate linear regression implicated age (ß = 0.330, p < 0.001), SMI (ß = -0.260, p < 0.001), albumin (ß = -0.245, p = 0.005), and sodium (ß = -0.179, p = 0.037) as independent risk factors for frailty. CONCLUSION: Sarcopenia is associated with multi-dimensional frailty in male patients with cirrhosis. It is tempting to incorporate sex-specific intervention with the purpose of mitigating frailty among inpatients.

A predictive nomogram incorporating gait speed for all-cause mortality in hospitalized cirrhotics.

OBJECTIVES: No tailored model incorporating physical frailty for 2-year mortality in cirrhosis is available for practitioners in general practice. Thus we aimed to develop a model based on laboratory results and physical frailty allowing clinicians for stratifying cirrhotics by using individual estimate. METHODS: One hundred and thirteen cases were assigned to the primary cohort, and all other 76 patients were regarded as the validation cohort. Multivariate Cox regression was performed, and a nomogram including five-meter gait speed (5MGS) were generated. The performance of the proposed model was assessed by C-index, calibration curve, and decision curve analysis (DCA). RESULTS: On multivariate analysis, the Model for End-Stage Liver Disease-Sodium, albumin and 5MGS were independent predictors for 2-year mortality in cirrhosis. A nomogram incorporating all these parameters achieved a C-index of 0.804 (95%CI, 0.731-0.877). The calibration curve implied optimal correspondence between the predicted survival and actual outcomes. Our model is useful in the clinical settings based on DCA. Similar results were observed in the validation cohort with a C-index of 0.796 (95%CI, 0.689-0.899). Moreover, 5MGS, as a surrogate of physical performance, significantly correlated with multiple domains of general frailty according to Frailty Index (our published data), including instrumental activities of daily living, self-reported health, social activity and falls. CONCLUSION: In conclusion, the nomogram incorporating 5MGS may represent an individualized tool for predicting mortality in cirrhosis for primary care physicians.

Myopenic obesity determined by visceral fat area strongly predicts long-term mortality in cirrhosis.

BACKGROUND: The impact of changes in body composition has proved to correlate with outcomes in cirrhosis, however, numerous issues remain elusive. The present study aimed to investigate the prognostic value of myopenic obesity (MO) on long-term mortality in cirrhosis. METHODS: We retrospectively analyzed 200 patients with cirrhosis. Body composition parameters including skeletal muscle index (SMI) and visceral fat area (VFA) were estimated by computed tomography images at the third lumbar vertebra level. We defined MO as a low SMI (male: SMI < 46.96 cm2/m2 and female: SMI < 32.46 cm2/m2) with BMI ≥ 25 kg/m2 or VFA ≥ 100 cm2 according to our previous publication. Patients were categorized into one of four body composition groups in terms of the presence or absence of myopenia and obesity. RESULTS: On the basis of VFA or BMI, the four group comparison demonstrated the prognosis was poor in MO, followed by myopenic/nonobesity (MN), nonmyopenic/obesity and nonmyopenic/nonobesity, in that order (log-rank test). Multivariate Cox analysis identified that MO (HR 2.498; 95% CI, 1.214-5.140; P = 0.013), MN (HR 2.763; 95% CI, 1.244-6.134; P = 0.013), age (HR 3.035; 95% CI, 1.904-4.839; P < 0.001), neutrophil-to-lymphocyte ratio (HR 1.142; 95% CI, 1.082-1.207; P < 0.001) and MELD (HR 1.140; 95% CI, 1.066-1.219; P = 0.001) were independently associated with 2-year mortality according to VFA classification. CONCLUSIONS: MO was an independent predictor of higher long-term mortality in cirrhosis. Prevention strategies by reducing visceral fat obesity rather than BMI should be the optimal target for MO management.

Scoparone as a therapeutic drug in liver diseases: Pharmacology, pharmacokinetics and molecular mechanisms of action.

Scoparone is an active and efficious ingredient of herbal medicine Artemisia capillaris Thunb, which has been used clinically in traditional Chinese medicine formula (e.g. Yin-Chen-Hao decoction) for the treatment of hepatic dysfunction, cholestasis and jaundice for over thousand years. More recently, scoparone has received increasing attention due to its multiple properties. In this comprehensive review, we provide the first summary of the pharmacological effects and pharmacokinetic characteristics of scoparone, and discuss future research prospects. The results implicated that scoparone possesses a wide spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-apoptotic, anti-fibrotic and hypolipidemic properties. Pharmacokinetic studies have addressed that isoscopoletin and scopoletin are major primary metabolites of scoparone. Moreover, hepatic dysfunction might promote bioavailability of scoparone due to limited intrinsic clearance. On the other hand, the bioavailability of multi-component including scoparone in certain TCM formula can also be enhanced by applying this formula at a high dose on account of their interacted effects. In view of good pharmacological actions, scoparone is anticipated to be a potential drug candidate for various liver diseases, such as acute liver injury, fulminant hepatitis, alcohol-induced hepatotoxicity, non-alcoholic fatty liver disease and fibrosis. However, further studies are warranted to clarify its molecular mechanisms and targets, elucidate its toxicity, and identify its interplay with other active ingredients of classical TCM formula in clinical settings.

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc- have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.

Incorporation of frailty estimated by gait speed within MELD-Na and the predictive potential for mortality in cirrhosis.

BACKGROUND: The 5 m gait speed (5MGS), a simple and reliable performance metric and surrogate indicator of frailty, consistently predicts adverse events in elders. Additionally, MELD-Na (model for end-stage liver disease-sodium) scores fail to capture nutritional and functional decline of cirrhotic patients that may confer excess mortality. We hypothesized that 5MGS might be associated with all-cause mortality, and that inclusion of frailty assessment within MELD-Na could improve the prediction of mortality in cirrhosis. METHODS: 5MGS was measured at baseline in 113 hospitalized cirrhotic patients. Survival status over 2 years and cirrhosis-related complications were recorded. We evaluated the prognostic value of 5MGS (as a continuous variable and as a dichotomous variable). The definition of slow versus preserved 5MGS was 0.8 ms-1 based on previous publication. Using Cox proportional hazards regression, a novel MELDNa-5MGS score was derived. Receiver operating characteristics (ROC) curves estimated discrimination between the new score model and established prognostic indices. RESULTS: The continuous 5MGS and slow 5MGS were independent predictors of all-cause mortality [5MGS: hazard ratio (HR) 0.133 (0.047-0.347), p < 0.001; slow 5MGS: HR 4.805 (1.536-15.026), p < 0.007]. The equation derived from Cox regression analysis was as follows: MELDNa-5MGS: MELD-Na score + 11 × slow 5MGS. The 2-year mortality in patients with high MELDNa-5MGS score was significantly higher (p < 0.001). Discriminatory power was significantly better for MELDNa-5MGS than MELD-Na score (AUC: 0.802 versus 0.724, p = 0.014 for 1 year; 0.773 versus 0.709, p = 0.044 for 2 years). CONCLUSION: In cirrhotic patients, 5GMS is an independent risk factor of mortality. Modification of MELD-Na to include frailty estimated by low 5GMS is related to improved prognostication of mortality.

Nitric oxide is involved in the oxytetracycline-induced suppression of root growth through inhibiting hydrogen peroxide accumulation in the root meristem.

Use of antibiotic-contaminated manure in crop production poses a severe threat to soil and plant health. However, few studies have studied the mechanism by which plant development is affected by antibiotics. Here, we used microscopy, flow cytometry, gene expression analysis and fluorescent dyes to study the effects of oxytetracycline (OTC), a widely used antibiotic in agriculture, on root meristem activity and the accumulation of hydrogen peroxide (H2O2) and nitric oxide (NO) in the root tips of tomato seedlings. We found that OTC caused cell cycle arrest, decreased the size of root meristem and inhibited root growth. Interestingly, the inhibition of root growth by OTC was associated with a decline in H2O2 levels but an increase in NO levels in the root tips. Diphenyliodonium (DPI), an inhibitor of H2O2 production, showed similar effects on root growth as those of OTC. However, exogenous H2O2 partially reversed the effects on the cell cycle, meristem size and root growth. Importantly, cPTIO (the NO scavenger) and tungstate (an inhibitor of nitrate reductase) significantly increased H2O2 levels in the root tips and reversed the inhibition of root growth by OTC. Out results suggest that OTC-induced NO production inhibits H2O2 accumulation in the root tips, thus leading to cell cycle arrest and suppression of root growth.

Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells.

OBJECTIVE: Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated. METHODS: In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay. Dose response curve analysis was performed in AGS and MKN-45 cells with stable ASNS knockdown to assess sensitivity to cisplatin. Xenograft experiment was performed to examine in vivo synergistic effects of ASNS depletion and cisplatin on tumor growth. Expression level of ASNS was evaluated in human patient samples using quantitative PCR. Kaplan-Meier curve analysis was performed to evaluate association between ASNS expression and patient survival. RESULTS: Transient knockdown of ASNS inhibited cell proliferation and colony formation in AGS and MKN-45 cells. Stable knockdown of ASNS conferred sensitivity to cisplatin in these cells. Depletion of ASNS and cisplatin treatment exerted synergistic effects on tumor growth in AGS xenografts. Moreover, ASNS was found to be up-regulated in human gastric cancer tissues compared with matched normal colon tissues. Low expression of ASNS was significantly associated with better survival in gastric cancer patients. CONCLUSION: ASNS may contribute to gastric cancer tumorigenesis and may represent a novel therapeutic target for prevention or intervention of gastric cancer.

A ratiometric fluorescent probe for in vivo tracking of alkaline phosphatase level variation resulting from drug-induced organ damage.

Clinical drug-induced organ toxicity and damage have been recognized as an important public health issue, and an effective approach capable of in vivo detection of biomarkers resulting from drug-induced organ damage is being actively pursued. Herein, we demonstrate a ratiometric fluorescent probe that can trace the variation in alkaline phosphatase (ALP, an organ damage biomarker) levels spatially in vivo. The probe was synthesized by incorporating a phosphate group and an amine-N-oxide group on a 1,8-naphthalimide derivative. The presence of ALP cleaves the phosphate group from naphthalimide and remarkably alters the probe's photophysical properties, thus achieving ratiometric detection of ALP. The incorporation of amine-N-oxide ensures excellent water solubility and biocompatibility, which guarantees the ratiometric detection of ALP in aqueous media and in the cells overexpressed with ALP. With a detection limit of 0.38 U L-1, the probe was successfully used in detecting ALP in human serum samples. Moreover, the probe can be employed to monitor and spatially map the endogenous variation in ALP levels in zebrafishes. This is the first observation, to our knowledge, of organ-scale ALP pattern in vivo as a result of clinical drug (APAP) induced damage.

Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms.

AIM: To explore whether clinical presentations of gastric small gastrointestinal tumors (GISTs) mimics gastrointestinal dyspepsia symptoms. METHODS: The endosonographic data of 167 patients who underwent endoscopic submucosal dissection at the Tianjin Medical University General Hospital, China between 2009 and 2011 were analyzed. GISTs and leiomyomas had a similar intragastric distribution and similar locations within the gastric wall. Therefore, patients with GISTs were chosen as the study group and those with leiomyomas were chosen as the control group. Dyspepsia symptom questionnaires were used to investigate and compare the gastrointestinal symptoms of patients with GISTs and those with gastric leiomyomas before and after endoscopic submucosal dissection (ESD). The questionnaires evaluated symptoms such as epigastric pain, heartburn, regurgitation, epigastric discomfort, nausea and vomiting, abdominal bloating, and eructation. Symptoms were assessed using a four-point scoring scale. RESULTS: GISTs were the most common gastric submucosal lesion (67 cases, 40.12%), followed by leiomyomas (38 cases, 22.75%). Both groups were similar in terms of gender distribution (P = 0.49), intragastric location (P = 0.525), and originating layer within the gastric wall (P = 0.449), but leiomyomas were more commonly found in the proximal fundus (P < 0.05). Overall, 94.2% of the patients with small GISTs and 93.5% of those with gastric leiomyomas experienced some dyspepsia; however, total symptom scores were significantly lower in the GIST group than in the leiomyoma group (1.34 ± 1.27 vs 2.20 ± 1.70, P < 0.05). Each component of the symptom score demonstrated a statistically significant improvement in the GIST patients after ESD (P < 0.05), including epigastric pain (0.80 ± 0.90 vs 0.13 ± 0.46), heartburn (0.63 ± 1.08 vs 0.13 ± 0.41), regurgitation (0.55 ± 0.87 vs 0.22 ± 0.57), epigastric discomfort (0.70 ± 0.98 vs 0.32 ± 0.47), nausea and vomiting (0.27 ± 0.62 vs 0.05 ± 0.21), abdominal bloating (0.70 ± 0.90 vs 0.27 ± 0.49), and eructation (0.36 ± 0.61 vs 0.21 ± 0.46). For leiomyoma patients, symptoms such as heartburn, nausea, vomiting, and eructation improved after treatment; however, these improvements were not statistically significant (P > 0.05). Thus, the pathophysiology of dyspepsia symptoms may be different between the two groups. CONCLUSION: Symptoms of gastric small GISTs may mimic those of functional dyspepsia. An alternative diagnosis should be considered in patients with functional dyspepsia and treatment failure.

Ratiometric fluorescence assay for γ-glutamyltranspeptidase detection based on a single fluorophore via analyte-induced variation of substitution.

The first ratiometric fluorescent probe for γ-glutamyltranspeptidase (GGT) was developed, which functions through GGT-induced variation of substitution and subsequent changes in photophysical properties. It can detect GGT in human serum, and be used to visualize the endogenous GGT in ovarian cancer cells.

Efficacy and safety of endoscopic submucosal dissection in treating gastric subepithelial tumors originating in the muscularis propria layer: a single-center study of 144 cases.

OBJECTIVE. Subepithelial tumors (SETs) in the stomach are usually considered benign. However, some do have potential for malignant transformation, especially when originating in the muscularis propria (MP). Our study aimed to evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for gastric SETs originating in MP. MATERIAL AND METHODS. A total of 145 gastric MP SETs in 144 patients were treated by ESD between September 2008 and December 2012. Characteristics of patients and SETs, therapeutic outcomes, pathologic characteristics, complications and follow-up outcomes were evaluated. RESULTS. Among the 144 patients, 104 were female (72.22%) and 40 were male (27.78%), and the mean age was 55.75 ± 11.29 years (range 18-78 years). The mean size of the tumors determined by endoscopic ultrasound (EUS) was 15.14 ± 9.70 mm (range 3-50 mm). En bloc complete resection was achieved in 134 of 145 tumors, giving a complete resection rate of 92.41%. The final histopathologic diagnoses included 52 leiomyomas, 89 gastrointestinal stromal tumors, 3 neurogenic tumors and 1 lipoma. Perforations occurred in 21 patients (14.48%) and were endoscopically repaired with clips or nylon bands. Intraoperative bleeding occurred in seven patients (4.83%) and was corrected with argon plasma coagulation (APC) or hot biopsy forceps. No local recurrence or distant metastasis was detected during a mean follow-up of 19.14 ± 10.29 months (range 3-51 months). CONCLUSIONS. ESD appears to be an effective and safe treatment for gastric SETs originating in MP.

Endoscopic submucosal dissection for gastrointestinal mesenchymal tumors adjacent to the esophagogastric junction: we need to do more.

OBJECTIVE: Extensive surgery is the mainstay of therapy for patients with gastrointestinal mesenchymal tumors (GIMTs) adjacent to the esophagogastric junction (EGJ). However, this modality is invasive and may interfere with anatomic consistency of the digestive tract. Therefore, we evaluated the feasibility, safety, and efficacy of endoscopic submucosal dissection (ESD) for GIMTs close to the EGJ and factors related to incomplete resection. PATIENTS AND METHODS: For 39 GIMTs adjacent to the EGJ in 39 consecutive patients, the baseline information, complications, and therapeutic outcomes were recorded. Subsequently, risk factors, focusing on age, sex, tumor size, extent, shape, perforation presence/absence, and histopathology, were analyzed. RESULTS: Complete removal of junctional GIMTs was achieved in 32 cases, giving an overall complete resection rate of 82%. The mean tumor size was 16.1±12.7 (median, 12; range, 4-50) mm. There were no major intra- and postoperative complications, but two small perforations were found. The final histopathologic diagnoses included 28 leiomyomas, 10 gastrointestinal stromal tumors, and 1 schwannoma. No local recurrence or distant metastasis was observed during a mean follow-up of 15.7±8.4 (median, 16; range, 6-35) months. Univariate analysis showed incomplete resection was associated with tumor shape and size. Multivariate regression analysis identified tumor irregularity (odds ratio=37.50, 95% confidence interval=4.253-330.627) as the single factor associated with incomplete resection. CONCLUSIONS: ESD is feasible and safe for well-selected patients with GIMTs adjacent to the EGJ. Irregular tumor shape should be considered as a technical difficulty while performing ESD. Oncologic outcomes need to be assessed with longer follow-up.

Endoscopic submucosal dissection of large gastrointestinal stromal tumors in the esophagus and stomach.

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract with potential for malignant transformation, are mainly treated by open surgery or laparoscopic resection. The aim of this retrospective study was to evaluate the clinical efficacy, safety, and feasibility of endoscopic submucosal dissection (ESD) for large-size (2-5 cm) GISTs in the esophagus and stomach. METHODS: A total of 31 patients with large-size GISTs in the esophagus (6 patients) and stomach (25 patients) underwent ESD between September 2008 and December 2011. Demographics, clinical data, therapeutic outcomes, complications, pathological characteristics, risk classification, and follow-up outcomes were recorded. RESULTS: ESD was successfully performed in 31 patients at age of 59.06 ± 7.23 years (range: 46-74). The mean time of the procedure was 70.16 ± 16.25 min (range: 40-105). Perforation for 2-10 mm occurred in six patients (19.35%) and was endoscopically repaired with clips or nylon bands, with no conversions to open surgery. Intraoperative bleeding occurred in three patients (9.68%) and was corrected with argon plasma coagulation or hot biopsy forceps. No mortalities occurred. The mean size of the resected tumors was 2.70 ± 0.72 cm (range: 2.0-5.0). Out of the 31 patients, 24 (77.42%) were at very low risk and 7 (22.58%) were at low risk. Positive rate of CD117, DOG-1, and CD34 were 83.87%, 12.90%, and 100%, respectively. A follow up for 14.29 ± 8.99 months (range: 3-39) showed no recurrence or metastasis. CONCLUSIONS: ESD appears to be an effective, safe, and feasible treatment for large-size GISTs in the esophagus and stomach.