Assessment of a Real-world Learning Curve for the Endoscopic Resection of Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Endoscopic resection (ER) is a proven treatment for gastric gastrointestinal stromal tumors (gGISTs). We aimed to assess the learning curve (LC) associated with ER for gGISTs and identify determinants. METHODS: We conducted an analysis of 289 patients who underwent the ER of gGISTs by an experienced endoscopist. To characterize the LC, we employed cumulative sum analysis of the duration of surgery. The participants were divided into an early phase (cases 1-50) and a later phase (case 51-289), which were compared. Furthermore, we identified risk factors for the conversion from endoscopic to laparoscopic resection (LR). RESULTS: The durations of surgery and hospitalization were shorter, and there were fewer complications and fasting days in the later phase. The conversion rates to LR were 6.0% and 2.5% in the early and later phases, respectively. The tumor diameter (≥3.0 cm) and invasion beyond the muscularis propria were significant risk factors for conversion to LR (odds ratio 17.92, 95% confidence interval 2.66-120.87; and 58.03, 6.40-525.84; respectively). CONCLUSIONS: The LC for ER of gGISTs lasts for approximately 50 cases. In addition, tumors ≥3.0 cm in diameter and those that invade beyond the muscularis propria are more likely to require conversion to LR.

Risk factors for postoperative complications in endoscopic resection of gastric gastrointestinal stromal tumors: a multi-center analysis.

BACKGROUND: Endoscopic resection (ER) is widely used in treating gastric gastrointestinal stromal tumors (gGISTs); however, complications occur frequently after resection. We aimed to determine factors associated with postoperative complications for ER of gGISTs. METHODS: This was a retrospective, multi-center, observational study. Consecutive patients who underwent ER of gGISTs at five institutes from January 2013 to December 2022 were analyzed. The risk factors for delayed bleeding and postoperative infection were assessed. RESULTS: A total of 513 cases were finally analyzed. Of 513 patients, 27 (5.3%) had delayed bleeding and 69 (13.4%) had a postoperative infection. Multivariate analysis indicated that risk factors for delayed bleeding were long operative time (OR = 50.655; 95% CI, 13.777-186.252; P < 0.001) and severe intraoperative bleeding (OR = 4.731, 95% CI, 1.139-19.658; P = 0.032), and risk factors for postoperative infection were long operative time (OR = 13.749, 95% CI, 6.884-27.461; P < 0.001) and perforation (OR = 4.339, 95% CI, 2.178-8.644; P < 0.001). CONCLUSIONS: Our study indicated the risk factors for postoperative complications in ER of gGISTs. Long operation time is a common risk factor for delayed bleeding and postoperative infection. Patients with these risk factors should be given careful observation postoperatively.

Development and validation of a preoperative difficulty scoring system for endoscopic resection of gastric gastrointestinal stromal tumor: a multi-center study.

BACKGROUND: Endoscopic resection (ER) is a promising technique for resecting gastric gastrointestinal stromal tumors (gGISTs); however, ER is technically challenging. This study aimed to develop and validate a difficulty scoring system (DSS) to determine the difficulty for ER of a gGIST. METHODS: This retrospective study enrolled 555 patients with gGISTs in multi-centers from December 2010 to December 2022. Data on patients, lesions, and outcomes of ER were collected and analyzed. A difficult case was defined as an operative time ≥ 90 min, or the occurrence of severe intraoperative bleeding, or conversion to laparoscopic resection. The DSS was developed in the training cohort (TC) and validated in the internal validation cohort (IVC) and external validation cohort (EVC). RESULTS: The difficulty occurred in 97 cases (17.5%). The DSS comprised the following: tumor size ≥ 3.0 cm (3 points) or 2.0-3.0 cm (1 point); location in the upper third of the stomach (2 points); invasion depth beyond the muscularis propria (2 points); lack of experience (1 point). The area under the curve (AUC) of DSS in IVC and EVC was 0.838 and 0.864, respectively, and the negative predictive value (NPV) was 0.923 and 0.972, respectively. The proportions of difficult operation in easy (score 0-3), intermediate (score 4-5), and difficult (score 6-8) categories were 6.5%, 29.4%, and 88.2% in the TC, 7.7%, 45.8%, and 85.7% in the IVC, and 7.0%, 29.4%, and 85.7% in the EVC, respectively. CONCLUSIONS: We developed and validated a preoperative DSS for ER of gGISTs based on tumor size, location, invasion depth, and endoscopists' experience. This DSS can be used to grade the technical difficulty before surgery.

Learning curve for endoscopic resection of gastric gastrointestinal stromal tumors: a single-center experience.

BACKGROUND: endoscopic resection (ER) is widely used in the treatment of gastric gastrointestinal stromal tumors (gGISTs). However, no studies have previously described the learning curve (LC) for ER of gGISTs. This study aimed to evaluate the LC based on multifarious operative outcomes. METHODS: one hundred consecutive patients who underwent ER of gGISTs by a single endoscopist from January 2017 to December 2022 were included. Patients were analyzed in groups of ten to minimize demographic differences, and operative time (OT), conversion rate, intraoperative and postoperative complication were assessed to evaluate the LC. Meanwhile, for the OT, the LC was further analyzed using the cumulative sum (CUSUM) method and patients were organized chronologically in three phases. RESULT: there was a statistically significant decrease in OT, conversion to laparoscopic surgery, and postoperative complication after 30 cases (median 80.0 min vs 56.0 min, p < 0.001; 10.0 % vs 0 %, p = 0.025; 33.3 % vs 10.0 %, p = 0.004), rate of intraoperative complications after 20 cases (15.0 % vs 1.3 %, p = 0.025). CUSUM chart demonstrated that OT increased dramatically before around 30 cases (phase 1) and decreased after 60 cases (phase 3), with a plateau phase in the middle 30 cases (phase 2). Among the three phases, the R0 resection and conversion rate were not significantly different. However, OT, intraoperative and postoperative complications were gradually decreased (p < 0.05). CONCLUSIONS: the LC of ER of gGISTs is approximately 60 cases. However, about 30 cases were sufficient to acquire skills to reduce complications and conversion rate during the ER procedure.

Automated machine learning to predict the difficulty for endoscopic resection of gastric gastrointestinal stromal tumor.

Background: Accurate preoperative assessment of surgical difficulty is crucial to the success of the surgery and patient safety. This study aimed to evaluate the difficulty for endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) using multiple machine learning (ML) algorithms. Methods: From December 2010 to December 2022, 555 patients with gGISTs in multi-centers were retrospectively studied and assigned to a training, validation, and test cohort. A difficult case was defined as meeting one of the following criteria: an operative time ≥ 90 min, severe intraoperative bleeding, or conversion to laparoscopic resection. Five types of algorithms were employed in building models, including traditional logistic regression (LR) and automated machine learning (AutoML) analysis (gradient boost machine (GBM), deep neural net (DL), generalized linear model (GLM), and default random forest (DRF)). We assessed the performance of the models using the areas under the receiver operating characteristic curves (AUC), the calibration curve, and the decision curve analysis (DCA) based on LR, as well as feature importance, SHapley Additive exPlanation (SHAP) Plots and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML. Results: The GBM model outperformed other models with an AUC of 0.894 in the validation and 0.791 in the test cohorts. Furthermore, the GBM model achieved the highest accuracy among these AutoML models, with 0.935 and 0.911 in the validation and test cohorts, respectively. In addition, it was found that tumor size and endoscopists' experience were the most prominent features that significantly impacted the AutoML model's performance in predicting the difficulty for ER of gGISTs. Conclusion: The AutoML model based on the GBM algorithm can accurately predict the difficulty for ER of gGISTs before surgery.

Risk factors for conversion from endoscopic resection to laparoscopic resection for gastric gastrointestinal stromal tumors.

OBJECTIVE: Endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) is a commonly used treatment; however, it is associated with a risk of conversion to laparoscopic resection (LR). This study was performed to identify factors influencing conversion from ER to LR and the effects of conversion on outcomes. METHODS: The clinicopathological features of patients treated for gGISTs from March 2010 to May 2021 were retrospectively collected. Endpoints included the determination of risk factors associated with LR conversion, with comparisons of surgical outcomes with and without conversion. Propensity score matching was performed to compare the two groups. RESULTS: In total, 371 gGISTs were analyzed. Sixteen patients required conversion from ER to LR. Propensity score matching demonstrated that invasion depth (muscularis propria with exophytic growth) and gGIST size (≥3 cm) were independent risk factors for conversion to LR. The procedure duration (median, 160.5 vs. 60.0 minutes), postoperative hospitalization duration (median, 8 vs. 6 days), and postoperative fasting duration (median, 5 vs. 3 days) were significantly longer in patients who underwent conversion to LR. CONCLUSIONS: Accurate preoperative measurements of tumor size and invasion depth may help determine more appropriate surgical approaches for patients with gGISTs.

Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

An evaluation of the use of double-curved endoscopes for gastric gastrointestinal stromal tumors.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is a standard treatment method for gastric gastrointestinal stromal tumors (gGISTs). Evidence of the safety and efficacy of a double-curved endoscope (DCE) in EFTR of gGISTs is limited. We aimed to compare the operative outcomes of DCE versus single-curved endoscopes (SCE) in EFTR of gGISTs. MATERIAL AND METHODS: This retrospective observational study was conducted at four Chinese tertiary institutes. From January 2019 to November 2021, 104 patients who underwent EFTR by SCE (n = 57) or DCE (n = 47) were enrolled. One-to-one propensity score matching (PSM) was performed between the two groups to compare the demographics and operative outcomes. RESULTS: All gGISTs were resected successfully with no recurrence during follow-up. The median (range) tumor size was 1.2 (0.5, 3.5) cm in DCE and 2.0 (0.6, 4.8) cm in SCE (p < .001), and the procedure time was shorter in the DCE group than in the SCE group (50.0 min vs. 62.0 min, p < .05). After PSM, 41 pairs were selected, and no difference was noted in demographics. The procedure time was also shorter in the DCE group than in the SCE group (50.0 min vs. 55.0 min, p < .05). Subgroup analysis showed that the DCE group had a shorter procedure time in the gastric fundus than the SCE group (47.0 min vs. 55.0 min, p < .05). In multiple linear regression analysis, significant factors related to prolonged procedure time were the type of endoscope of SCE and larger tumor size (p < .05). CONCLUSIONS: EFTR of gGISTs using DCE is safe and effective. Compared with SCE, DCE had an advantage in terms of operative time, especially in the gastric fundus.

Learning curve for endoscopic resection of gastric gastrointestinal stromal tumors: a single-center experience

Background: endoscopic resection (ER) is widely used in the treatment of gastric gastrointestinal stromal tumors (gGISTs). However, no studies have previously described the learning curve (LC) for ER of gGISTs. This study aimed to evaluate the LC based on multifarious operative outcomes. Methods: one hundred consecutive patients who underwent ER of gGISTs by a single endoscopist from January 2017 to December 2022 were included. Patients were analyzed in groups of ten to minimize demographic differences, and operative time (OT), conversion rate, intraoperative and postoperative complication were assessed to evaluate the LC. Meanwhile, for the OT, the LC was further analyzed using the cumulative sum (CUSUM) method and patients were organized chronologically in three phases. Result: there was a statistically significant decrease in OT, conversion to laparoscopic surgery, and postoperative complication after 30 cases (median 80.0 min vs 56.0 min, p < 0.001; 10.0 % vs 0 %, p = 0.025; 33.3 % vs 10.0 %, p = 0.004), rate of intraoperative complications after 20 cases (15.0 % vs 1.3 %, p = 0.025). CUSUM chart demonstrated that OT increased dramatically before around 30 cases (phase 1) and decreased after 60 cases (phase 3), with a plateau phase in the middle 30 cases (phase 2). Among the three phases, the R0 resection and conversion rate were not significantly different. However, OT, intraoperative and postoperative complications were gradually decreased (p < 0.05). Conclusions: the LC of ER of gGISTs is approximately 60 cases. However, about 30 cases were sufficient to acquire skills to reduce complications and conversion rate during the ER procedure (AU)

Transcriptomes reveal the involved genes in the sea urchin Mesocentrotus nudus exposed to high flow velocities.

Despite the importance of flow velocity in marine ecosystems, molecular mechanisms of the water flow induced behavioral and growth changes remain largely unknown in sea urchins. The present study compared the gene expressions of the sea urchin Mesocentrotus nudus at high flow velocities (10 cm/s and 20 cm/s) and low flow velocity (2 cm/s) using transcriptomes. A total of 490 and 470 differentially expressed genes (DEGs) were discovered at 10 cm/s and 20 cm/s, respectively. There were 235 up-regulated and 255 down-regulated genes at 10 cm/s, 213 up-regulated and 257 down-regulated genes at 20 cm/s, compared with sea urchins at 2 cm/s. Further, there were 72 overlapped DEGs involved in regulation at both 10 cm/s and 20 cm/s. Gene Ontology (GO) functional annotation showed that DEGs were mainly enriched to cellular process, cell part, binding, and metabolism process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that DEGs were enriched in three pathways related to amino acid metabolism and lipid metabolism. A number of genes related to growth and metabolism of sea urchins were mobilized in high flow velocity environment. We further highlighted a muscle-associated gene ankyrin-1, which is correlated with the movement of tube feet at different flow velocities. The present study provides valuable information on the molecular mechanisms of changed behaviors and growth when sea urchins are exposed to high flow velocity.

Risk Factors and Timing of Additional Surgery after Noncurative ESD for Early Gastric Cancer.

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery. Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days, n = 11), delayed surgery (>30 days, n = 11) after ESD, and upfront surgery (n = 59) were compared. Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups. Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.

Carryover effects of long-term high water temperatures on fitness-related traits of the offspring of the sea urchin Strongylocentrotus intermedius.

It is important to study the fitness of marine invertebrates in exposure to high water temperature. We studied whether the long-term high temperatures work on the fitness-related traits (righting behavior, covering behavior, foraging behavior, Aristotle's lantern reflex, body size) of S. intermedius whose parents (males and females) were exposed to ambient or high temperatures (~3 °C higher than the ambient) for a long period of time. The present study found that test diameter, wet body weight and test weight of offspring were not significantly different between temperature treatments, indicating that the parental sea urchins in exposure to high temperatures develop no carryover effects on the body size of the offspring sea urchins. We found no significant difference in foraging behavior, Aristotle's lantern reflex, lantern length and lantern weight of sea urchins after their parents had experienced long-term high temperatures. In addition, no significant change was found in the righting and covering behaviors of sea urchins whose parents were at long-term high temperatures. These results indicate that no significant lasting effects exhibited in the fitness-related behaviors and tissue size after their parents were exposed to high temperatures for a long time. The crushing force of test and test thickness showed no significant difference in the offspring of S. intermedius, no matter whether their parents were exposed to long-term high temperatures or not. The current results enrich our understanding that the parental sea urchin experiencing long-term high temperatures probably develop no carryover effects on the test of their offspring. We found that sea urchins whose parents were exposed to long-term elevated temperatures showed a significantly higher lantern length/test diameter and a significantly lower test height/test diameter in offspring sea urchins due to the thermal experience of their parents, showing the plasticity of lantern and test of offspring sea urchins in response to the thermal experience of their parents. Together with our previous investigation, the present study indicates that small sea urchins are less susceptible to the carryover effects of high temperatures in comparison with the developmental stages of embryos and larvae.

Detection of Microsatellite Instability from Circulating Tumor DNA by Targeted Deep Sequencing.

Currently, microsatellite instability (MSI) detection is limited to tissue samples with sufficient tumor content. Detection of MSI from blood has been explored but confounded by low sensitivity due to limited circulating tumor DNA (ctDNA). We developed a next-generation sequencing-based algorithm, blood MSI signature enrichment analysis, to detect MSI from blood. Blood MSI signature enrichment analysis development involved three major steps. First, marker sites that can effectively distinguish high MSI (MSI-H) from microsatellite stable tumors were extracted. Second, MSI signature enrichment analysis was performed based on hypergeometric probability, under the null hypothesis that plasma samples have similar MSI-H and microsatellite stable read coverage patterns for particular marker sites as the white blood cells from the training data set. Finally, enrichment scores of marker sites were normalized, and all markers were collectively considered to determine the MSI status of a plasma sample. In vitro dilution experiments with cell lines and in silico simulation experiments based on mixtures of MSI-H plasma and paired white blood cell DNA demonstrated 98% sensitivity and 100% specificity at a minimum of 1% ctDNA and 91.8% sensitivity and 100% specificity with 0.4% ctDNA. An independent validation cohort of 87 colorectal cancer patients with orthogonal confirmation of MSI status of tissues confirmed performance, achieving 94.1% sensitivity (16/17) and 100% specificity (27/27) for samples with ctDNA >0.4%.

Transcriptomes shed light on transgenerational and developmental effects of ocean warming on embryos of the sea urchin Strongylocentrotus intermedius.

Ocean warming increasingly endangers the fitness of marine invertebrates. Transgenerational effects (TE) potentially mitigate the impacts of environmental stress on the embryos of marine invertebrates. The molecular mechanisms, however, remain largely unknown. Using high-throughput RNA sequencing technology, we investigated the gene expression patterns of embryos (the gastrula stage) of the sea urchin Strongylocentrotus intermedius at different developmental temperatures, whose parents were exposed to long-term (15 months) elevated temperature (A) or not (B). The temperatures at which adults were held for ~4 weeks prior to the start of the experiment (21 °C for A and 18 °C for B) were also used for the development of offspring (high: 21 °C and ambient (laboratory): 18 °C) resulting in four experimental groups (HA and HB at 21 °C, and LA and LB at 18 °C). The embryos were sampled ~24 h after fertilization. All samples were in the gastrula stage. Twelve mRNA libraries (groups HA, HB, LA, LB, 3 replicates for each group) were established for the following sequencing. Embryos whose parents were exposed to elevated temperatures or not showed 1891 significantly different DEGs (differentially expressed genes) at the ambient developmental temperature (LB vs LA, LB as control) and 2203 significantly different DEGs at the high developmental temperature (HB vs HA, HB as control), respectively. This result indicates complex molecular mechanisms of transgenerational effects of ocean warming, in which a large number of genes are involved. With the TE, we found 904 shared DEGs in both LB vs LA (LB as control) and HB vs HA (HB as control) changed in the same direction of expression (i.e., up- or down-regulated), indicating that parental exposed temperatures affect the expression of these genes in the same manner regardless of the development temperature. With developmental exposure, we found 198 shared DEGs in both HB vs LB (HB as control) and HA vs LA (HA as control) changed in the same direction of expression. Of the 198 DEGs, more genes were up-regulated at high developmental temperature. Interestingly, embryos whose parents were exposed to high temperature showed fewer differently expressed DEGs between high and low developmental temperatures than the individuals whose parents were exposed to ambient temperature. The results indicate that gene expressions are probably depressed by the transgenerational effect of ocean warming. The roles of hsp70 and hnf6 in thermal acclimation are highlighted for future studies. The present study provides new insights into the molecular mechanisms of the transgenerational and developmental effects of ocean warming on the embryos of sea urchins.

Snare-assisted endoscopic resection of gastric subepithelial tumors originating from the muscularis propria layer: a multicenter study.

BACKGROUND AND AIM: Although successful endoscopic resection of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer has been frequently reported, it requires a relatively complicated technique and has a high perforation rate. In this retrospective study, we evaluated the efficacy and safety of the snare-assisted endoscopic resection (SAER) method which is performed using a snare and insulated-tip (IT) knife via a single-channel endoscope to reduce the perforation rate. METHODS: In this study, fifty-six patients with gastric SETs originating from the MP layer treated by the SAER method at three institutions between July 2017 and December 2017 were reviewed. The procedure involved multiple steps as shown in Fig. 2. Data were obtained on demographics, SET features, histopathological diagnoses, procedure time, en bloc resection rate, R0 resection (negative margins) status, and adverse events. RESULTS: Endoscopic resection was successfully performed in all patients. The median overall procedure time was 43.5 min (range 26-106 min). The mean size of resected specimens was 19.73 mm (range 10-33 mm). The overall rate of en bloc resection was 96.4% (54/56). In addition, the perforation rate was 7.1% (4/56), and defects in the stomach wall were very small and easily closed using metallic clips. No postprocedural bleeding occurred in any case. CONCLUSIONS: The SAER method is an effective, safe, less costly technique for the removal of some gastric SETs originating from the MP layer with an appropriate size.

Light intensity regulates phototaxis, foraging and righting behaviors of the sea urchin Strongylocentrotus intermedius.

Small sea urchins Strongylocentrotus intermedius (1-2 cm of test diameter) are exposed to different environments of light intensities after being reseeded to the sea bottom. With little information available about the behavioral responses of S. intermedius to different light intensities in the environment, we carried out an investigation on how S. intermedius is affected by three light intensity environments in terms of phototaxis, foraging and righting behaviors. They were no light (zero lx), low light intensity (24-209 lx) and high light intensity (252-2,280 lx). Light intensity had obvious different effects on phototaxis. In low light intensity, sea urchins moved more and spent significantly more time at the higher intensity (69-209 lx) (P = 0.046). S. intermedius in high light intensity, in contrast, spent significantly more time at lower intensity (252-690 lx) (P = 0.005). Unexpectedly, no significant difference of movement (average velocity and total distance covered) was found among the three light intensities (P > 0.05). Foraging behavior of S. intermedius was significantly different among the light intensities. In the no light environment, only three of ten S. intermedius found food within 7 min. In low light intensity, nine of 10 sea urchins showed successful foraging behavior to the food placed at 209 lx, which was significantly higher than the ratio of the number (two of 10) when food was placed at 24 lx (P = 0.005). In the high light intensity, in contrast, significantly less sea urchins (three of 10) found food placed at the higher light intensity (2,280 lx) compared with the lower light intensity (252 lx) (10/10, P = 0.003). Furthermore, S. intermedius showed significantly longer righting response time in the high light intensity compared with both no light (P = 0.001) and low light intensity (P = 0.031). No significant difference was found in righting behavior between no light and low light intensity (P = 0.892). The present study indicates that light intensity significantly affects phototaxis, foraging and righting behaviors of S. intermedius and that ~200 lx might be the appropriate light intensity for reseeding small S. intermedius.

Transgenerational effects of UV-B radiation on egg size, fertilization, hatching and larval size of sea urchins Strongylocentrotus intermedius.

Transgenerational effects are important for phenotypic plasticity and adaptation of marine invertebrates in the changing ocean. Ultraviolet-B (UV-B) radiation is an increasing threat to marine invertebrates. For the first time, we reported positive and negative transgenerational effects of UV-B radiation on egg size, fertilization, hatchability and larval size of a marine invertebrate. Strongylocentrotus intermedius exposed to UV-B radiation showed positive transgenerational effects and adaptation on egg size, hatching rate and post-oral arm length of larvae. Negative transgenerational effects were found in body length, stomach length and stomach width of larvae whose parents were exposed to UV-B radiation. Sires probably play important roles in transgenerational effects of UV-B. The present study provides valuable information into transgenerational effects of UV-B radiation on fitness related traits of sea urchins (at least Strongylocentrotus intermedius).

GLI1 overexpression promotes gastric cancer cell proliferation and migration and induces drug resistance by combining with the AKT-mTOR pathway.

Hedgehog (HH) pathway significantly affected the pathogenesis of Gastric cancer (GC), but the multiple uncanonical HH pathways that are mediated by Zinc Finger protein GLI1 (GLI1) are still unclear. In the present work, we evaluated GLI1 and p-AKT expression in GC using immunohistochemistry (IHC) analysis. GLI1 and AKT specific shRNA was transfected into GC cell lines to investigate the cross-regulation between HH pathway and AKT-mTOR pathway. The effect of GLI1 and p-AKT on proliferation, migration, and drug resistance were examined. Moreover, a mouse xenograft model of GC was established to verify the role of GLI1 and p-AKT in promoting drug sensitivity in vivo. Our results suggested the clinicopathological factors and prognosis by the differential expression of GLI1 and p-AKT in GC patients. GLI1 was activated by the AKT-mTOR pathway. Co-expression of GLI1 and p-AKT was associated with cell viability, migration, and drug resistance and indicated a poor prognosis in GC patients. Agents targeted against both GLI1 and p-AKT may reverse drug-resistance and achieve better inhibition than agents targeted against a single molecule. There was a significant correlation between the high expression of GLI1 and p-AKT in GC. Additionally, our study confirmed the activity of the AKT-mTOR-GLI1 axis, which provided a new viable field for GC treatment.

Analysis of Endoscopy Intervention in Postesophagectomy Anastomotic Leak: A Retrospective Study.

BACKGROUND: Anastomotic leak after esophagectomy is one of the most challenging complications resulting in a high morbidity and mortality and prolonged hospitalization. The aim of this retrospective study was to access the impact of endoscopy intervention in anastomotic leak. METHODS: A retrospective review was conducted at our hospital from January 2008 to December 2016. In total, 263 patients who were diagnosed with an anastomotic leak after esophagectomy and underwent endoscopy examination were included in this study. First, all patients were divided into two groups based on a single criteria-whether they received endoscopy intervention or not-and comparisons were conducted between the two groups. Second, we categorized all patients into three groups based on the diameter of the anastomotic leak (group I: <5 mm; group II: 5-15 mm; group III: >15 mm). Detailed analyses were made for each group. Factors we considered included demographic factors, the length of postoperative hospital stay, the amount of medical expenditure, limited days of oral intake, and the incurrence of complications. Data relating to those factors were collected and then analyzed using standard statistic tools. RESULTS: In general, the difference between endoscopy intervention and conservative measure was significant. Moreover, the hospital stay (p < 0.001; p = 0.018), medical expenditure (p < 0.001; p = 0.003), limited days of oral intake (p < 0.001; p = 0.019), and postoperative complications such as hemorrhage (p < 0.001; p = 0.036), tracheoesophageal fistula (p = 0.002; p = 0.017), and anastomosis stricture (p = 0.03; p = 0.026) were significantly lower among patients who received endoscopy intervention in groups II and III. However, no significant difference was identified between endoscopy intervention and conservative measure in group I. CONCLUSIONS: Endoscopy intervention is safe and effective in the diagnosis and treatment of postesophagectomy anastomotic leak. Especially for patients with a diameter of anastomotic leaks greater than 5 mm, the advantages of endoscopy intervention should not be neglected.

Transcriptomes reveal genes involved in covering and sheltering behaviors of the sea urchin Strongylocentrotus intermedius exposed to UV-B radiation.

Although the potential link exists between behavioral responses to UV-B radiation and the maximization of fitness, molecular mechanisms of these UV-B induced behaviors remain poorly understood. For the first time, we investigated the transcriptomes of covered (CB), sheltered (SB) and non-protected (NA) sea urchins Strongylocentrotus intermedius exposed to UV-B radiation. A total of 330 differentially expressed genes were revealed by transcriptome comparisons. By comparing with the group NA, we found 79 up-regulated and 118 down-regulated genes in SB group, as well as 26 up-regulated and 67 down-regulated genes in group CB. There were 34 up-regulated genes and 52 down-regulated genes in group SB, compared with group CB. These differentially expressed genes failed to enrich either Gene Ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG), only except an enrichment in KEGG. We highlighted TRPA1 and Opsin as key neurobiological genes involved in the molecular mechanisms of covering and sheltering behaviors of sea urchins exposed to UV-B radiation. What's more, other identified genes provide valuable resources for future investigations on the molecular basis of covering and sheltering behaviors of sea urchins.